Alkaloids: Chemical and Biological Perspectives

Alkaloids: Chemical and Biological Perspectives Related Titles of Interest Books GAWLEY & AUBE: Principles of Asymmet...

Author: S.W. Pelletier

111 downloads 1897 Views 16MB Size Report

This content was uploaded by our users and we assume good faith they have the permission to share this book. If you own the copyright to this book and it is wrongfully on our website, we offer a simple DMCA procedure to remove your content from our site. Start by pressing the button below!
Report copyright / DMCA form

DOWNLOAD PDF

Alkaloids: Chemical and Biological Perspectives

Related Titles of Interest Books GAWLEY & AUBE: Principles of Asymmetric Synthesis GRIBBLE & GILCHRIST: Progress in Heterocyclic Chemistry, Volume 10 GRIBBLE & GILCHRIST: Progress in Heterocyclic Chemistry, Volume 11 SESSLER & WEGHORN: Expanded Contracted and Isomeric Porphyrins PELLETIER: Alkaloids: Chemical & Biological Abstracts, Volume 9 PELLETIER: Alkaloids: Chemical & Biological Abstracts, Volume 10 PELLETIER: Alkaloids: Chemical & Biological Abstracts, Volume 11 PELLETIER: Alkaloids: Chemical & Biological Abstracts, Volume 12 PELLETIER: Alkaloids: Chemical & Biological Abstracts, Volume 13 WONG & WHITESIDES: Enzymes in Synthetic Organic Chemistry

Major Reference Works BARTON, NAKANISHI, METH-COHN: Comprehensive Natural Products Chemistry KATRITZKY & REES: Comprehensive Heterocyclic Chemistry I CD-Rom KATRITZKY, REES & SCRIVEN: Comprehensive Heterocyclic Chemistry II

Journals BIOORGANIC & MEDICINAL CHEMISTRY BIOORGANIC & MEDICINAL CHEMISTRY LETTERS CARBOHYDRATE RESEARCH HETEROCYCLES (distributed by Elsevier) PHYTOCHEMISTRY TETRAHEDRON TETRAHEDRON: ASYMMETRY TETRAHEDRON: LETTERS

Full details of all Elsevier Science publications, and a free specimen copy of any Elsevier Science journal, are available on request from your nearest Elsevier Science office.

Alkaloids: Chemical and Biological Perspectives Volume Fourteen

Edited by

S. William Pelletier Institute for Natural Products Research and Department of Chemistry The University of Georgia, Athens

1999

PERGAMON An Imprint of Elsevier Science

Amsterdam - Lausanne - New York - Oxford - Shannon - Singapore - Tokyo

ELSEVIER SCIENCE Ltd The Boulevard, Langford Lane Kidlington. Oxford OX5 1GB, UK

C 1999 Elsevier Science Ltd. All rights reserved.

This work it protected under copyright by Elsevier Science, and the following terms and conditions apply to its use: Photocopying Single photocopies of single chapters may be made for pcrsond »we wallowed by naUcmal copyright laws. Permi»sion of the Publither and payment of a fee isrequiredfor all other photocopying, including multiple or systematic copying, copying for advertising or promotional purposes, resale, and allformsof document delivery. Special rales are availableforeducational institutions that wish to make photocopies for non-profit educational classroom use. Permissions may be sought directly from Elsevier Science Righto ft Permissions Department, PO Box 800. Oxford OX5 1DX, UK; phone: (+44) 1865 843830. fax: (444) 186S 853333. e-mail: permissions9elsevier.co.uk. You may also contact Rights ft Permissions directly through Elsevier's home page (http://www.elsevier.nl), selecting first 'Customer Support*, then 'General Information', then 'Permissions Query Form. In the USA. users may dear permissions and make payments through me Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers. MA 01923. USA; phone: (978) 7508400. fax: (978) 7504744. and in the UK through the Copyright Licensing Agency Rapid Clearance Service (CLARCS). 90 Tottenham Court Road. London W1P 0LP. UK; phone: (444) 171 631 5555; fax: (444) 171 631 5500. Other countries may have a localreprographicrightsagency for payments. Derivative Works Tables of contents may be reproduced for internal circulation, but permission of Elsevier Science isrequiredfor external resale or distribution of such material. Permission of die Publisher isrequiredfor all other derivative works, including compilations and translations. Electronic Storage or Usage Permission of the Publisher isrequiredto store or use electronically any material contained in this work, including any chapter or part of a chapter. Except as outlined above, no part of this work may be reproduced, stored ma retrieval system or tnnsmra^ electronic, mechanical, photocopying,recordingor otherwise, without prior written permission of the Publisher. Address permissionsrequeststo: Elsevier Science Righto A Permissions Department, at die mail, fax and e-mail addresses noted above. Noresponsibilityis assumed by the Publisher for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in die material herein. Because of rapid advances in die medical sciences, in particular, independent verification of diagnoses and drug dosages should be made.

First edition 1999 Library of Congress Cataloging in Publication Data A catalog record from the Library of Congress has been applied for. British Library Cataloguing in Publication Data A catalogue record from the British Library has been applied for.

ISBN:

0 0 8 043665 X

Transferred to digital printing 2006

Dedicated to the memory of

Roger Adams (1889-1971) Roger Adams was one of the great leaders who influenced the development of chemistry in the United States. He was born on June 2, 1889 (Boston), a member of the famous family which produced two presidents of the United States. After graduation (B.A., 1905) he obtained his Ph.D. (1912, Harvard) and spent three years (1913-1916) as an instructor in the Chemistry Department of Harvard University. During this period he spent some time in Germany to work with Richard Willstatter on the synthesis of some pyrrolomethanes related to the structure of chlorophyll. After returning from Germany, he joined the faculty of the University of Illinois in Urbana (1916) and served as chairman of the chemistry department from 1926-1954. Adams was interested in the study of natural products and established the correct structure of the pyrroloquinazoline alkaloid vasicine (1936). He contributed largely to the study of alkaloids of the Crotalaria and Senecio species which cause liver cirrhosis in grazing cattle. Other pyrrolidine alkaloids studied by him were: monocrotaline, seneciphylline, retrorsine, trichodesmine, jacobine and grantianine. He determined the structures of the "necic acids" such as monocrotic and monocrotalic acids, and the bases isolated by hydrolysis of the pyrrolidine alkaloids. He corrected the structure of riddellic acid, obtained by hydrolysis of riddelliine, an alkaloid from Senecio riddellii. Adams worked on the structures of gossypol from cotton seed meal, cannabinols from marijuana, and chalmoogra oil. He worked for three decades on the stereochemistry of molecules with restricted rotations about a single bond. Adams's contributions to the growth of organic chemistry are extraordinary. He published 425 papers, guided 184 Ph.D. students, 50 postdoctorals and consulted for many major chemical companies. Adams was solely responsible for starting the series of volumes of Organic Syntheses (1921) and later Organic Reactions (1942).

B. S. Joshi

v

This Page Intentionally Left Blank

Contributors Toh-Seok Kam, Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, MALAYSIA. Jie Jack Li, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, 2800 Plymouth Road, Ann Arbor, Michigan 48105, U.S.A. Paul L. Schiff, Jr., Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pennsylvania 15261, U.S.A.

vii


Preface Volume 14 of this series presents three interesting reviews of research on alkaloids. Chapter 1, by Paul L. Schiff, Jr. is a monumental effort, presenting a selective, comprehensive tabular review of research on the bisbenzylisoquinoline alkaloids, with an analysis of the respective alkaloid types. The chapter should serve as a very useful tool for the bench research scientist who is involved in the isolation and elucidation of structures of bisbenzylisoquinoline alkaloids. Moreover, the data in these tables provides the botanical distribution and occurrence (family, genus, species) of the various classes of these alkaloids. The alkaloids are also categorized by their molecular weights and structural types. Chapter 2, by Toh-Seok Kam is a review of alkaloids derived from Malaysian flora. Malaysia's position near the Equator confers on it a tropical climate characterized by high temperatures, humidity, and rainfall, conditions favorable for plant life that has resulted in a rich flora of about 15,000 species of higher plants. This review concentrates on work published during the past twenty years and where appropriate compares the occurrence of alkaloids with studies of similar plants from countries neighboring to Malaysia, especially Thailand and Indonesia. Chapter 3 by Jie Jack Li presents a collection of very interesting total syntheses of naturally occurring indole alkaloids where palladium chemistry plays a central role in the syntheses. Five different types of palladium-mediated reactions are treated: (1) oxidative cyclization reactions promoted by palladium (II) species; (2) transmetallation reactions with organoboranes, organostannanes, and organozinc reagents; (3) inter- and intramolecular Heck reactions; (4) reactions with 7t-allylpalladium as the intermediate; and (5) reactions using C-N bond formation as the key step for the synthesis. Each chapter in this volume has been reviewed by at least one specialist in the field. The editor thanks these reviewers for their important contributions to this volume. Indexes for both subjects and organisms are provided. The editor invites prospective contributions to write him about topics for review in future volumes of this series. S. William Pelletier Athens, Georgia July 15, 1998 IX


Contents of Previous Volumes Volume 1 1. The Nature and Definition of an Alkaloid S. William Pelletier 2. Arthropod Alkaloids: Distribution, Functions, and Chemistry Tappey H. Jones and Murray S. Blum

33

3. Biosynthesis and Metabolism of the Tobacco Alkaloids Edward Leete

85

4. The Toxicology and Pharmacology of Diterpenoid Alkaloids M. H. Benn and John M. Jacyno 5. A Chemotaxonomic Investigation of the Plant Families of Apocynaceae, Loganiaceae, and Rubiaceae by Their Indole Alkaloid Content M. Volkan Kisaburek, Anthony J.M. Leeuwenberg, and Manfred Hesse

153

211

Volume 2 1. Some Uses of X-ray Diffraction in Alkaloid Chemistry Janet Finer-Moore, Edward Arnold, and Jon Clardy 2. The Imidazole Alkaloids Richark K. Hill 3. Quinolizidine Alkaloids of the Leguminosae: Structural Types, Analyses, Chemotaxonomy, and Biological Properties A. Douglas Kinghorn and Manuel F. Balandrin

1

49

105

4. Chemistry and Pharmacology of Maytansinoid Alkaloids Cecil R. Smith, Jr. and Richard G. Powell 5.

13 C and Proton NMR Shift Assignments and Physical Constants of Ci9-Diterpenoid Alkaloids S. William Pelletier, Naresh V. Mody, Balawant S. Joshi, and Lee C. Schramm

149

XI

Contents of Previous Volumes

Volume 3 1. The Pyridine and Piperidine Alkaloids: Chemistry and Pharmacology Gabor B. Fodor and Brenda Colasanti 2. The Indolosesquiterpene Alkaloids of the Annonaceae Peter G. Waterman

9]

3. Cyclopeptide Alkaloids Madeleine M. Joullie and Ruth F. Nutt

113

4. Cannabis Alkaloids Mahmoud A. ElSohly

169

5. Synthesis of Lycopodium Alkaloids Todd A. Blumenkopf and Clayton H. Heathcock

185

6. The Synthesis of Indolizidine and Quinolizidine Alkaloids of Tylophora, Cryptocarya, Ipomoea, Elaeocarpus, and Related Species R. B. Herbert

241

7. Recent Advances in the Total Synthesis of Pentacyclic Aspidosperma Alkaloids Larry E. Overman and Michael Sworin

275

Volume 4 1. Amphibian Alkaloids: Chemistry, Pharmacology and Biology John W. Daly and Thomas F. Spande 2. Marine Alkaloids and Related Compounds William Fenical 3. The Dimeric Alkaloids of the Rutaceae Derived by Diels-Alder Addition Peter G. Watermann 4. Teratology of Steroidal Alkaloids Richard F. Keeler

275

331

389

Contents of Ftovious

Volume 5 1. The Chemistry and Biochemistry of Simple Indolizidine and Related Polyhydroxy Alkaloids Alan D. Elbein and Russell J. Molyneux 2. Structure and Synthesis of Phenanthroindiolizidine Alkaloids and Some Related Compounds Emery Gellert

1

55

3. The Aporphinoid Alkaloids of the Annonaceae Andre Cave, Michel Leboeuf, Peter G Waterman

133

4. The Thalictrum Alkaloids: Chemistry and Pharmacology Paul L Schiff, Jr.

271

5. Synthesis of Chephalotaxine Alkaloids Tomas Hudlicky, Lawrence D. Kwart, and Josephine W. Reed

639

Volume 6 1. Chemistry, Biology and Therapeutics of the Mitomycins William A. Remers and Robert T. Dorr

1

2. Alkaloids of Tabernaemontana Species Teris A. van Beek and Marian A.J.T. van Gessel

75

3. Advances in Alkaloid Total Synthesis via Iminium Ions, a-Aminocarbanions and a-Aminoradicals David J. Hart 4. The Biosynthesis of Protoberberine Alkaloids Christopher W. W. Beecher and William J. Kelleher 5. Quinoline, Acridone and Quinazoline Alkaloids: Chemistry, Biosynthesis and Biological Properties Michael F. Grundon

227

297

339


Volume 7 1. Homoerythrina and Related Alkaloids /. Ralph C. Bick andSirichai Panichanum 2. Carbon-13 NMR Spectroscopy of Steroidal Alkaloids Pawan K. Agrawal, Santosh K. Srivastava, and William Gaffleld 3. Carbon-13 and Proton NMR Shift Assignments and Physical Constants of Norditerpenoid Alkaloids S. William Pelletier and Balawant S. Joshi

1

43

297

Volume 8 1. Curare Norman G. Bisset 2. Alkaloid Chemistry and Feeding Specificity of Insect Herbivores James A. Saunders, Nichole R. O'Neill, and John T. Romero

151

3. Recent Advances in the Synthesis of Yohimbine Alkaloids Ellen W. Baxter and Patrick S. Mariano

197

4. The Loline Group of Pyrrolidine Alkaloids

320

Richard G. Powell and Richard J. Petroski Volume 9 1. Taxol M.E. Wall and M. C. Wani

1

2. The Synthesis of Macroline Related Sarpagine Alkaloids Linda K. Hamaker and James M. Cook

23

3. Erythrina Alkaloids Amrik Singh Chawla and Vijay K. Kapoor

85

4. Chemistry, Biology and Chemoecology of the Pyrrolizidine Alkaloids Thomas Hartmann and Ludger Witte

155

5. Alkaloids from Cell Cultures of Aspidosperma Quebracho-Bianco P. Obitz, J. Stockigt, L A. Mendonza, N Aimi and S.-i. Sakai

235


6. Fumonisins Richard G Powell and Ronald D. Planner

247

Volume 10 1. Alkaloids from Australian Flora /. R. C. Bick 2. Pyridine and Piperidine Alkaloids: An Update Marilyn J. Schneider

155

3. 3-Alkylpiperidine Alkaloids Isolated from Marine Sponges in the Order Haplosclerida Raymond J. Andersen, Rob W. M. Van Soest and Fangming Kong

301

4. P-Carboline and Isoquinoline Alkaloids from Marine Organisms Bill J. Baker

357

Volume 11 1.

The Thalictrum Alkaloids: Chemistry and Pharmacology (1985 - 1995) Paul L. Schiff, Jr.

2.

Taxine Giovanni Appendino

237

3.

The Alkaloids of South American Menispermaceae Mary D. Menachery

269

4.

The Chemistry and Biological Activity of Calystegines and Related Nortropane Alkaloids Russell J. Molyneux, Robert J. Nash, and Naoki Asano

303

5.

Polyhydroxylated Alkaloids that Inhibit Glycosidases Robert J. Nash, Naoki Asano, and Alison A. Watson

345

Contents of Previous Volumes Volume 12 1.

Acronycine-type Alkaloids: Chemistry and Biology Francois Tillequin, Sylvie Michel and Alexios-Uandros Skaltsounis

1

2.

Solarium Steroid Alkaloids — an Update Helmut Ripperger

103

3.

Synthesis and Structure-Activity Studies of Lissoclinum Peptide Alkaloids Peter Wipf

187

4.

Pyroglutamate as a Chiral Template for the Synthesis of Alkaloids Michael B. Smith

229

5.

Analysis of Alkaloids by Capillary Electrophoresis and Capillary Electrophoresis — Electrospray Mass Spectrometry Joachim Stockigt, Matthias Unger, Detlef Stockigt, and Detlev Belder

289

6.

Oxidation of Anthelmentic Marcofortine A, an Indole Alkaloid Byung H. Lee, Michael F. Clothier, and Gabe I Kornis

343

Volume 13 1.

Alkaloids from Amphibian Skins John W. Daly, H. Martin Garraffo and Thomas F. Spande

1

2.

Naturally Occurring Cyclotryptophans and Cyclotryptamines Uffe Anthoni, Carsten Christophersen and Per Halfdan Nielson

163

3.

Recent Research on Pyrrole Alkaloids Philip W. LeQuesne, Ying Dong and Todd A. Blythe

237

4.

Recent Developments in the Chemistry of Norditerpenoid and Diterpenoid Alkaloids Balawant S. Joshi and S. William Pelletier

289

5.

New Approaches to the Syntheses of Piperidine, Izidine, and Quinazoline Alkaloids by Means of Transition Metal Catalyzed Carbonylations Iwao Ojima and Donna M. Iula

371

Contents 1. The Bisbenzylisoquinoline Alkaloids - A Tabular Review Paul L Schiff, Jr. 2. Alkaloids from Malaysian Flora Toh-SeokKam 3. Applications of Palladium Chemistry to the Total Syntheses of Naturally Occurring Indole Alkaloids JieJackLi

437

Subject Index

505

Organism Index

529

1 235


Chapter One

The Bisbenzylisoquinoline Alkaloids A Tabular Review Paul L. Schiff, Jr. Department of Pharmaceutical Sciences School of Pharmacy University of Pittsburgh Pittsburgh, Pennsylvania 15261 CONTENTS 1. 2. 3. 4. 5. 6. 7. 8. 9.

INTRODUCTION 3 AN ALPHABETICAL TABULAR COMPILATION OF THE BISBENZYLISOQUINOLINE ALKALOIDS 4 A NUMERIC TABULAR COMPILATION OF THE BISBENZYLISOQUINOLINE ALKALOIDS 36 AN ALPHABETICAL TABULAR COMPILATION OF THE BOTANICAL SOURCES (GENERA) OF THE BISBENZYLISOQUINOLINE ALKALOIDS 77 AN ALPHABETICAL TABULAR COMPILATION OF THE BOTANICAL SOURCES (FAMILIES) OF THE BISBENZYLISOQUINOLINE ALKALOIDS 112 A TABULAR COMPILATION OF THE CALCULATED MOLECULAR WEIGHTS OF THE BISBENZYLISOQUINOLINE ALKALOIDS 133 A TABULAR COMPILATION OF THE STRUCTURAL TYPES OF THE BISBENZYLISOQUINOLINE ALKALOIDS 147 ALKALOIDS WITH DUPLICATIVE NOMENCLATURE 165 AN ANALYSIS OF THE DISTRIBUTION OF THE BISBENZYLISOQUINOLINE ALKALOIDS BY STRUCTURAL TYPE 168 9.1. O n e Diphenyl Ether Linkage (Tail-to-Tail) 168 9.1.1. Typel(6,7,ll*,12-6,7,12*) 168 9.1.2. Type la (6,7,11*. 12-5,6,7,12*) 175 9.1.3. TVpeIb(6,7,10,ll*,12-6.7,12*) 176 9.1.4. Type 0 (6,7,10*,12,13-6,7,12*) 176 9.1.5. Type H a (6,7,10*,12,13-6,7,11,12*) 177 9.1.6. Type IIb(6,7,10*,l 1,12-6,7,11,12*) 177 9.1.7. Typeffl(5,6,7,ll*,12-5,6,7,12*) 178 9.2. O n e Diphenyl Ether Linkage (Head-to-Tail) 180 9.2.1. TypeV(6,7,ll*,12-6,7*,12) 180 9.2.2. TypeVa(6,7,10*,12,13-6,7*,ll,12) 180 9.2.3. TypeVb(6,7,10*,ll,12.13-6,7*,ll,12) 181 9.2.4. Type Vc (6,7,10,12*-6,7*,12) 181

2

P.L. Schiff, Jr. 9.2.5. TypeVd(6,7,12*-6,7*,8,12) 9.3. One Diphenyl Linkage (Tail-to-Tail) 9.3.1. TVpe XXVH [6,7,12-6,7,12(11-11)] 9.4. One Diphenyl Ether Linage (Head-to-Head) and One Diphenyl Linage (Tail-toTail) 9.4.1. Type IV [6,7,8M2-6,7*,12(11-11)] 9.5. One Diphenyl Ether Linage (Head-to-Head) and One Diphenyl Ether Linage (Tail-to-Tail) 9.5.1. TypeVI(6,7*,ir,12-6,7,8*,12*) 9.5.2. Type Via (6,7M0,11M2-6,7,8*,12*) 9.5.3. Type VII (6,7*,ir,12-5,6,7,8*,12*) 9.5.4. TypcVffl(6,7,8MlM2-6,7M2*) 9.5.5. TypeDC(5,6,7,8*,llM2-6,7*,12*) 9.5.6. Type X (6,7,8*,11*, 12,13-6,7*. 12*) 9.5.7. TypeXa(6,7,8*,10,llM2-6,7*,12+) 9.5.8. Type Xb (6,7*,8,10,1IV 2-6,7*, 12*) 9.5.9. TypeXI(6,7,8*,ll*,12-6*,7,12*) 9.5.10. TypeXn(6,7,8*,ir,12-5*,6,7,12*) 9.5.11. TypeXna(5,6,7,8*,llM2-5*,6,7,12+) 9.5.12. TypeXIII(5*,6,7,llU2-5,6,7,8*,12*) 9.5.13. Type XIV (6,7*,1 1*,12-5*,6,7,12*) 9.5.14. Type XlVa (5,6,7*, 1 lM2-5*,6,7f 12*) 9.5.15. Type XV (5*,6,7,11*, 12-6,7*. 12*) 9.5.16. Type XVI (5*,6,7,11M2-6*,7,12+) 9.5.17. Type XVII (5,6,7,8*,10,12,13*-6,7*,12*) 9.6. One Diphenyl Ether Linage (Head-to-Tail) and One Diphenyl Ether Linage (Head-to-Tail) 9.6.1. TypeXX(6,7,8*,12*-6,7,8U2*) 9.6.2. TypeXXI(6,7,8*,llM2-6,7M2*) 9.7. Two Diphenyl Ether Linkages (Head-to-Head) and One Diphenyl Linkage (Tail-to-Tail) 9.7.1. TypeXVm[6,7*,8U2-6*,7M2(l 1-11)] 9.7.2. Type XIX [5,6,7*,8M2-6*,7M2(11-11)] 9.7.3. Type XDCa[5,7*,8M2-6*,7M2(l 1-11)] 9.8. One Diphenyl Ether Linkage (Head-to-Tail) and One Benzylphenyl Ether Linkage (Head-to-Tail) 9.8.1. TypeXXn(6,7,8,12*-6,7,8*[7-12]) 9.8.2. Type XXHa(6,7,8,1 lM2-6,7*[7-12]) 9.9. Two Diphenyl Ether Linkages (Head-to-Head) and One Diphenyl Ether Linkage (Tail-to-Tail) 9.9.1. TypeXXni(6*,7MlM2-6,7*.8M2 i ) 9.9.2. TypeXXma(6*.7Ml#,12-5,6,7*,8M2#) 9.9.3. TypeXXIIIa(6,7*,8Mli.12-6,74.8*.12i) 9.9.4. TypeXXVin(6,7*,8Vl i ,12-6*,7\12 i ) 9.10. One Diphenyl Ether Linkage and One Benzylphenyl Ether Linkage (Head-to Head) and One Diphenyl Ether Linkage (Tail-to-Tail)

182

182 182 184 184 190 190 202 203 204 220 222 224 226 226 229 232 232 234 236 238 238 239 241 241 244 250 250 253 255 256 256 258 259 259 266 268 269 271

The Bisbenzylisoquinoline Alkaloids - A Tabular Review 9.10.1. Type XXV (6,7,8*,llM2,13-6,7*,12*[8-6]) 9.11. One Diphenyl Ether Linkage and One Benzylphenyl Ether Linkage (Head-to-Tail) and One Diphenyl Ether Linkage (Head-to-Tail) 9.11.1. Type XXVI (6,7,8*.12*-6,7,8M2*[11-7])

1.

3 271

272 272

INTRODUCTION*

Over the last twenty years, no less than five tabular reviews describing the bisbenzylisoquinoline alkaloids have appeared [1-5]. These works have detailed the botanical sources, as well as the physical and spectral data, for over 430 different alkaloids. Pharmacological activities, analytical methods, and significant biosynthetic pathways have also been featured. Since I have been the author of four of these reviews [2-5], it occurred to me that a collation of selective tables featured in these reviews into a single, defined chapter would perhaps serve as a contribution to those engaged in research in this field. Toward that end, I offer the reader a selective comprehensive tabular review of these alkaloids, with an analysis of the respective alkaloid types. This work should not be considered as a definitive academic treatise of the subject, but rather as a useful pragmatic tool for the bench research scientist who is actively involved in the isolation and elucidation of structure of bisbenzylisoquinoline alkaloids. A consideration of the data in these tables, as well as the analysis provided in the last section, permits the reader to understand the botanical distribution and occurrence (family, genus, species) of the various classes of bisbenzylisoquinoline alkaloids. In addition, the alkaloids are also categorized according to their molecular weights and structural types. In order to maintain a consistency between this chapter and the previous reviews [1-5], the work in this chapter continues to utilize the alkaloid numbering system and structural-type nomenclature presented in the first review of the series [1], and maintained throughout the next four reviews [2-5]. The numbering of the skeleton and the systematic numerical classification describing the oxygenation and dimerization patterns of the alkaloids generally follow the convention established by Shamma and Moniot [483], and Guinaudeau et al. [129], as exemplified by:.

This chapter is dedicated to my children: Anne-Marie, Elizabeth Anne, Paul Edmund, and Mary Denise. As you have been born, beginning in 1964 and concluding in 1992, I have been blessed with your presence. May God go with you all as you walk through His world.

4

P.L.Schiff,Jr.

In order to retain a sense of consistency that encompasses decades of work, the alkaloids in this chapter have been drawn such that the Ring C terminus of the diphenyl ether bridge between Ring C and Ring C is always at C-12\ This has resulted in the representation of four alkaloids that bear numbers in their names in a "flipped" position in comparison to the manner in which they were found in the original reviews [1-5]. These four alkaloids include: 1,2dehydrokohatamine (289), 1,2-dehydrokohatine (290), 5-hydroxyapateline (309), and 5hydroxytelobine (310). Each of these compounds has been drawn with the Ring C terminus of their Ring C - Ring C diphenyl ether bridge at C-12'. The appearance of the molecules is thus such that the numbers in their names should assume "prime" nomenclature, eg 1,2dehydrokohatamine (289) appears is if it really is 1',2'-dehydrokohatamine, etc. I have not chosen to make this nomenclature change in the tables because of the historic precedent involved, and the confusion that it would produce, particularly to the novice in this field. Finally, I have not undertaken the condensation of the spectral data in these tables into a focussed offering that would compliment the work here presented. It is not because I believe that such a work should not be done, but because this chapter is now very lengthy as it is, and also because I have simply "run of steam" for the present time. I hope that the reader will forgive me this failure. Finally, it has been almost forty years since my curiosity and interest in this group of alkaloids began, in those early years as a student of Professor Jack L. Beal in his course in Pharmacognosy in the College of Pharmacy at The Ohio State University in 1959-1960. This continued in my years as his graduate student, and then under the tutelage of Professor Raymond W. Doskotch during my doctoral studies. To these two men, I owe much, and I have learned that I can only partially repay that debt by passing on a little bit of them through me to my students. It is my hope that this spirit of tradition and integrity will continue to walk, hand-in-hand, from advisor to student, through the years and centuries to come.

2.

AN A L P H A B E T I C A L T A B U L A R B1SBENZYLISOQUINOLINE ALKALOIDS

COMPILATION

OF

THE

Table 1

272 Ambrimine C3gH44OsN2:656.3097 Hernandia nymphaeifolia (Presl) Kubirtzki [Biasoletlia nymphaeifolia Presl, Hernandia peltata (Meissn.)] (Hernandiaceae)[6] 394 Angchibangkine Pachygone dasycarpa Kurz (Menispermaceae)[7]

CJ5HM05N2:562.2468

225 Antioquine Pseudoxandra aff. lucida Fries (Annonaceae)[8]

C37H40O6N2:608.2886

The Blsbenzyllsoqnlnollne Alkaloids - A Tabular Review

5

Table 1. Continued 187 Apateline C34H3205N2:548.2311 Albertisia laurifolia (Menispermaceae)[9] Albertisia papuana Becc. (Menispermaceae)[10] Daphnandra apatela Schodde (Monimiaceae)[l 1] Guatteria guianensis (Aublet) R.E. Fries (Annonaceae)[ 12] Pachygone loyaltiensis Diels (Menispermaceae)[13] 273 Aquifoline Mahonia aquifolium (Pursh) Nutt. (Berberidaceac)[14] 31

C36H3lO6N2:594.2730

Aromoline (Thalicrine) CMH3gO6N2:594.2730 Abuta splendida Krukoff and Moldenkc (Menispermaceae)[15] Albertisia laurifolia (Menispermaceae)[9] Albertisia papuana Becc. (Menispermaceae)[16] Berberis aristata DC. (Berberidaceae) [see Berberis flohbunda Wall ex. Don (Berberidaceae)][17] Berberis boliviano Lechl. (Berberidaceae)[18] Berberis bumeliaefolia Schneid. (Berberidaceae)[ 18] Berberis cretica L. (Berberidaceae)[19] Berberis jloribunda Wall ex. Don (Berberidaceae)[also known as Berberis arisata DC. (Berberidaceae)] [ 17] Berberis koreana Palib. (Berberidaceae)[20] Berberis laurina (Thunb.) Billbg. (Berberidaceae)[18] Berberis nummularia Bge. (Berberidaceae)[21 ] Berberis orthobotrys Bienert ex Aitch. (Berberidaceae)[78] Berberis stolonifera (Berberidaceae)[23] Berberis turcomanica Kar. (Berberidaceae)[24] Berberis waziristanica (Berberidaceae)[25] Daphnandra aromatica F.M. Bailey (Monimiaceae)[26] Daphnandra tenuipes Perk. (Monimiaceae)[27] Doryphora aromatica Schodde (Monimiaceae)[28] Guatteria guianensis (Aublet) R.E. Fries (Annonaceae)[12] Mahonia aquifolium (Pursh) Nutt. (Berberidaceae)[29] Stephania cepharantha Hayata (Menispermaceae)[30-33] Stephania pierrii Diels (Menispermaceae)[34] Thalictrum cultratum Wall. (Ranunculaceae)[35] Thalictrum fortunei S. Moore (Ranunculaceae)[36] Thalictrum lucidum L. (Ranunculaceae)[37] Thalictrum minus L. var. microphyllum Boiss. (Ranunculaceae)[38] Thalictrum rugosum Ait. (Ranunculaceae)[also called Thalictrum glaucum Desf. (Ranunculaceae)][39] Thalictrum thunbergii DC. (Ranunculaceae)[40,41] Triclisia patens Oliv. (Menispermaceae)[42]

P.L.SchifT,Jr. Table 1. Continued

171 Artifact (No. 16) Cyclea peltata Diels (Menispermaceae)[43]

C39H4406N2C12:707.2259

56 Atherospermoline Atherosperma moschatum L. (Monimiaceae)[44] Pachygone dasycarpa Kurz (Menispermaceae)[7]

C36H3gO6N2:594.2730

390 Auroramine C3gH40OgN2:652.2785 Gyrocarpus americanus Jacq. (Hernandiaceae)[also called Gyrocarpus jacquini Roxb. (Hernandiaceae)] [45] 257 Baluchistanamine Berberis baluchistanica Ahrendt (Berberidaceae)[46]

C37H3gOgN2:638.2628

188 Baluchistine Berberis baluchistanica Ahrendt (Berberidaceae)[47]

C36H3gO6N2:594.2730

93

Belarine 03^0^:608.2886 Berberis laurina (Thunb.) Billbg. (Berberidaceae)[ 18,48]

218 Berbacolorflammine (1,2,3,4-Tetradehydrolimacine) C37H37O6N2*:605.2652 Pycnarrhena longifolia (Decne. ex Miq.) Becc. (Menispermaceae)[49,50] 57

Berbamine C37H40O6N2:608.2886 Atherosperma moschatum L. (Monimiaceae)[51 ] Berberis aggregata (Berberidaceae)[52] Berberis amurensis Rupr. (Berberidaceae)[53] Berberis aristata DC.. (Berberidaceae)[see Berberis floribunda Wall ex. Don (Berberidaceae)][ 17,54] Berberis aquifolium Pursch (Berberidaceae)[56] Berberis asiatica Roxb. ex DC. (Berberidaceae)[57] Berberis boliviano Lechl. (Berberidaceae)[18] Berberis brandisiana Ahrendt (Berberidaceae)[58] Berberis bumeliaefolia Schneid. (Berberidaceae)[18] Berberis chilensis Gill, ex Hook. (Berberidaceae)[59] Berberis cretica L. (Berberidaceae)[19] Berberis dictyoneura (Berberidaccae)[52] Berberis floribunda Wall ex. Don (Berberidaceae)[also known as Berberis arisata DC.. (Berberidaceae)][ 17,54] Berberis fortunei Lindl. (Berberidaceae)(See (Hort.) Fedde (Berberidaceae)[55]) Berberis fracisci-ferdinandi (Berberidaceae)[52] Berberis heterobotrys Wolf. (Berberidaceae)[60]

The Bisbenzylisoquinoline Alkaloids - A Tabular Review

7

Table 1. Continued

Berberis heteropoda Schrenk (Berberidaceae)[see Berberis vulgaris L. (Berberidaceae)][61 ] Berberis iliensis (Berberidaceae)[62] Berberisjaponic a R.Br. (Berberidaceae)(See Mahoniajaponica DC. (Berberidaceae)[55]) Berberis julianae Schneid. (Berberidaceae)[63] Berberis kawakamii Hayata (Berberidaceae)[64] Berberis koreana Palib. (Berberidaceae)[20] Berberis lambertii R.N. Parker (Berberidaceae)[65] Berberis lycium (Royle) (Berberidaceae)[66-68] Berberis mingetsensis Hayata (Berberidaceae)[69] Berberis morrisonensis Hayata (Berberidaceae)[69] Berberis oblonga (Regl.)(Berberidaceae)[70] Berberis orthobotrys Bienert ex Aitch. (Berberidaceae)[78] Berberis paucidentata Rusby. (Berberidaceae)[ 18] Berberis petiolaris Nail (Berberidaceae)[71] Berberis poiretii (Berberidaceae)[72,73] Berberis pseudothunbergii (Berberidaceae)[52] Berberis regeliana (Berberidaceae)[74) Berberis sibirica Pall. (Berberidaceae)[75] Berberis stolonifera (Berberidaceae)[23,76] Berberis swaseyi Buckey (Berberidaceae)[77] Berberis thunbergii DC. (Berberidaceae)[79,80] Berberis tinctoria Leschen (Berberidaceae)(also designated as Berberis aristata DC. (Berberidaceae)[81 ] Berberis virgetorum (Berberidaceae)[82] Berberis vulgaris L. (Berberidaceae)[also called Berberis heteropoda Schrenk (Berberidaceae)][61,83-86] Berberis wilsoniae Hemsl. et Wils. (Berberidacaeae)[87] Berberis zebiliana (Berberidaceae)[88] Cyclea barbata (Wall.) Miers (Menispermaceae)[89,90] Isopyrum thalictroides L. (Ranunculaceae)[91] Limaciopsis loangensis Engl. (Menispermaceae)[92] Mahonia aquifolium (Pursh) Nutt. (Berberidaceae)[29,93-95] Mahonia fortunei (Hort.) Fedde (Berberidaceae)[55] Mahonia griffithii Takeda (Berberidaceae)[96] Mahonia japonica DC. (Berberidaceae)[55] Mahonia lomariifolia Takeda (Berberidaceae)[97] Mahonia morrisonensis Takeda (Berberidaceae)[97] Mahonia philippinensis Takeda (Berberidaceae)[98) Mahonia swaseyi Fedde (Berberidaceae)(See Berberis swaseyi Buckey (Berberidaceae)[77]) Pycnarrhena australiana F. Muell. (Menispermaceae)[99]

P.L.Schiff,Jr. Table 1. Continued Pycnarrhena manillensis F. Muell. (Menispermaceae) or Vidal (Menispermaceae)[ 100,101 ]Pycnarrhena novoguineensis Miq. (Menispennaceae)[22] Stephania cepharantha Hayata (Menispermaceae)[30,32,102-105] Stephania sasakii Hayata (Menispermaceae)[106] Stephania tetrandra S. Moore (MenispermaceaeXdetected; not isolated)[107] Thalictrum foetidum L. (Ranunculaceae)[108] Thalictrum pedunculatum Edgew. (Ranunculaceae)[109] 274 Berbamine-2'p-N-Oxide Berberis brandisiana Ahrendt (Berberidaceae)[58]

C37H4o07N2:624.2836

1

0^^0^2:596.2886

Berbamunine Berberis amurensis Rupr. (Berberidaceae)[82,110] Berberis boliviano Lechl. (Berberidaceae)[18] Berberis brachypoda (Berberidaceae)[82] Berberis circumserrata (Berberidaceae)[82] Berberis cretica L. (Berberidaceae)[19] Berberis dasystachya (Berberidaceae)[82] Berberis diaphana (Berberidaceae)[82] Berberis dictyoneura (Berberidaceae)[82] Berberis dubia (Berberidaceae)[82] Berberis ferdinandi-coburgii (Berberidaceae)[82] Berberis gyalaica (Berberidaceae)[82] Berberis henryana (Berberidaceae)[82] Berberis heteropoda Schrenk (Berberidaceae)[l 11-113] Berberis iliensis (Berberidaceae)[62] Berberis integerrima Bge. (Berberidaceae)[114] Berberis jamesiana (Berberidaceae)[82] Berberis julianae Schneid. (Berberidaceae)[82] Berberis kansuensis (Berberidaceae)[82] Berberis nummularia Bge. (Berberidaceae)[21] Berberis oblonga (Regl.XBerberidaceae)[115] Berberis poiretii (Berberidaceae)[82] Berberis polyantha (Berberidaceae)[82] Berberis prattii (Berberidaceae)[82] Berberis sargentiana (Berberidaceae)[82] Berberis silva-taroucana (Berberidaceae)[82] Berberis soulieana (Berberidaceae)[82] Berberis stolonifera (Berberidaceae)[23,76] Berberis turcomanica Kar. (Berberidaceae)[116] Berberis valdiviana (Berberidaceae)[82] Berberis vernae (Berberidaceae)[82] Berberis vulgaris L. (Berberidaceae)[84,86]

The Blsbenzyllsoqoinoline Alkaloids - A Tabular Review Table 1. Continued

Pseudoxandra sclerocarpa Maas (Annonaceae)[117] Stephania pierhi Diels (Menispermaceae)[34] 275 Berbilaurine Berberis laurina (Thunb.) Billbg. (Berberidaceae)[ 18]

C36H38O6N2:594.2730

32

C34H3406N2:566.2417

N,N'-Bisnoraromoline Albertisia papuana Becc. (Menispermaceae)[10] Pachygone loyaltiensis Diels (Menispermaceae)[13] Pycnarrhena ozantha Diels (Menispermaceae)[ 118]

276 2,2'-Bisnorguattaguianine C36H38O6N2:594.2730 Guatteria guianensis (Aublet) R.E. Fries (Annonaceae)[ 119] 277 Bisnorobamegine Pycnarrhena ozantha Diels (Menispermaceae)[120]

C34H3406N2:566.2417

278 2,2'-Bisnorphaeanthine Albertisia papuana Becc. (Menispermaceae)[10]

C36H38O6N2:594.2730

279 Bisnorthalrugosine Pycnarrhena ozantha Diels (Menispermaceae)[ 120]

C35H36O6N2:580.2573

189 Calafatimine Berberis bwcifolia Lam. (Berberidaceae)[121]

C38H40O7N2:636.2836

190 Calafatine Berberis bwcifolia Lam. (Berberidaceae)[121-123] Berberis horrida (Berberidaceae)[124]

C39H4407N2:652.3149

226 Calafatine-2'a-N-Oxide Berberis bwcifolia Lam. (Berberidaceae)[125,126]

C39H44O8N2:668.3098

227 Calafatine-2'P-N-Oxide Berberis bwcifolia Lam. (Berberidaceae)[125,126]

€^0^2:668.3098

280 Candicusine C%H38O6N2:594.2730 Curarea candicans (L.C. Rich) Barneby and R Krukoff (Menispermaceae)[127-129] 281 Caryolivine C36H34O6N2:590.2417 Caryomene olivascens Bameby et Krukoff (Menispermaceae)[74]

10


33

Cepharanoline C36H3606N2:592.2573 Stephania cepharantha Hayata (Menispermaceae)[32,102,104] Stephania epigeae Diburong (Menispermaceae)[130]

34

Cepharanthine C37H3gO6N2:606.2730 Stephania cepharantha Hayata (Menispermaceae)[32J02,104,105,131] Stephania epigeae Diburong (Menispermaceae)[132,133] Stephania erecta Craib. (Menispermaceae)[134,135] Stephania pierrii Diels (Menispermaceae)[34] Stephania sasakii Hayata (Menispermaceae)[106] Stephania sinica Diels (Menispermaceae)[136] Stephania suberosa Forman (Menispermaceae)[137]

282 Cepharanthine-2'p-N-Oxide Stephania suberosa Forman (Menispermaceae)[137]

C37H3gO?N2:622.2679

258 Chenabine Berberis lycium (Royle) (Berberidaceae)[138]

C37H40O7N2:624.2836

228 Cheratamine C36H34O7N2:606.2366 Cocculus pendulus (Forsk.) Diels (Menispermaceae)[ 139] 229 Chillanamine Berberis buxifolia Lam. (Berberidaceae)[123]

C37H4207N2:626.2992

129 Chondocurarine C3gH4406N2:624.3199 Chondodendron tomentosum Ruiz and Pavon (Menispermaceae)[140] 130 Chondocurine [Chondrocurine, (+)-Tubocurine] C3AH3gO6N2:594.2730 Chondodendron tomentosum Ruiz and Pavon (Menispermaceae)[141,142] Cyclea barbata (Wall.) Miers (Menispermaceae)[143] Cyclea madagascariensis Baill. (Menispermaceae)[144] Peruvian Curare [145] 131 Chondrofoline C37H40O6N2:608.2886 Chondodendron platiphyllum Miers (Menispermaceae)[146] Cleistopholis staudtii Engl, et Diels (Annonaceae)[147] Uvaria .»- a A. DC.. (Annonaceae)[148] 145 Cissampareine Cissampelos pareira L. (Menispermaceae)[149]

C37H38O6N2:606.2730

The BisbenzylisoquinoUne Alkaloids - A Tabular Review

11

Table 1. Continued 395 Cissampentin Cissampelos fasciculata Benth. (Menispermaceae)[ 150] 35

C37H40O6N2:608.2886

Coclobine C37H3gO6N2:606.2730 Anisocycla cymosa Troupin (Menispermaceae)[151] Cocculus trilobus D C (Menispermaceae)[152] Guatteria guianensis (Aublet) R.E. Fries (Annonaceae)[12)

396 Cocsiline C35H3406N2:578.2417 Cocculus pendulus (Forsk.) Diels (Menispermaceae)[153] 397 Cocsilinine C33H30O6N2:550.2104 Cocculus pendulus (Forsk.) Diels (Menispermaceae)[153] 152 Cocsoline C34H3205N2:548.2311 Albertisia laurifolia (Menispermaceae)[9] Albertisia papuana Becc. (Menispermaceae)[16,10] Anisocycla cymosa Troupin (Menispermaceae)[154] Cocculus leaebe DC. (Menispermaceae)[155] Cocculus pendulus (Forsk.) Diels (Mcnispermaceae)[139,153,156] Synclisia scabrida Miers (Menispermaceae)[157,158] 398 Cocsoline-2'P-N-Oxide Anisocycla cymosa Troupin (Menispermaceae)[ 159]

C34H32O6N2:564.2260

153 Cocsuline (Efirine, Trigilletine) C„H3405N2:562.2468 Albertisia laurifolia (Menispermaceae)[9] Albertisia papuana Becc. (Menispermaceae)[10,16] Anisocycla gradidieri H. Bn. (Menispermaceae)[165] Cocculus leaebe DC.. (Menispermaceae)[155] Cocculus pendulus (Forsk.) Diels (Menispermaceae)[139,153,156,161,166] erroneously identified as Andrachne cordifolia Muell., O.F. (Euphorbiaceae)[160]) Pachygone dasycarpa Kurz (Menispermaceae)[7] Synclisia scabrida Miers (Menispermaceae)[157,158] Triclisia dictyophylla Diels (Menispermaceae)[167] Triclisia gilletii (DeWild.) Staner (Menispermaceae)[168-170] Triclisia patens Oliv. (Menispermaceae)[168] 231 Cocsuline-N-2-Oxide Cocculus hirsutus Diels (Menispermaceae)[171]

C35H3406N2:578.2417

164 Cocsulinine ^5^0^:578.2417 Cocculus pendulus (Forsk.) Diels (Menispermaceae)[153,156]

12

P.L.SchhT,Jr. Table 1. Continued

219 Colorflammine (r,2',3',4'-Tetradehydrolimacusine) C37H37O6N2+:605.2652 Pycnarrhena longifolia (Decne. ex Miq.) Becc. (Menispermaceae)[49,50] 283 Cordobimine Crematosperma sp. (Annonaceae)[172]

C36H3606N2:592.2573

284 Cordobine Crematosperma sp. (Annonaceae)[ 172]

C37H40O6N2:608.2886

399 Costaricine Nectandra salicifolia (H.B.K.) Nees (Lauraceae)[173]

C„H38O6N2:582.2730

285 Cultithalminine Thalictrum cultratum Wall. (Ranunculaceae)[35]

C36H36O7N2:608.2522

259 Curacautine Berberis buxifolia Lam. (Berberidaceae)[123]

C39H4209N2:682.2891

400 Curicycleatjenine Cyclea atjehensis Forman (Menispermaceae)[174]

C3lH3lO?N2:634.2679

401 Curicycleatjine Cyclea atjehensis Forman (Menispermaceae)[ 174]

C37H36O7N2:620.2523

132 (+)-Curine [Bebeerine, Chondodendrine] C36H3gO6N2:594.2730 A buta candicans Rich ex D C (Menispermaceae)[146] Buxus sempervirens L. (Buxaceae)[also called Buxus wallichiana Baill. (Buxaceae)][176] Buxus wallichiana Baill. (Buxaceae)[also called Buxus sempervirens L. (Buxaceae)][176] Chondodendron microphylum (Eichl.) Moldenke (Menispermaceae)[ 146] Cissampelos pareira L. (Menispermaceae)[(+/-)-Curine dimethiodide][476] Cyclea barbata (Wall.) Miers (Menispermaceae)(132 or 133)[177,178] Cyclea hainanensis Merr. (Menispermaceae)(132 or 133)[175] Nectandra rodiei R. Schomb. (Lauraceae)[also known as Ocotea rodiei (Lauraceae)][176] Ocotea rodiei (Lauraceae)[also known as Nectandra rodiei R. Schomb. (Lauraceae)][l 76] 133 (-)-Curine [(-)-Bebeerine] C36H3lO6N2:594.2730 Aristolochia indica L. (Aristolochiaceae)[179] Chondodendron platiphyllum Miers (Menispermaceae)[146] Chondodendron tomentosum Ruiz and Pavon (Menispermaceae)[ 141,142,200] Chondendron toxicoferum (Wedd.) Kruk. et Mold. (Menispermaceae)[201] Cissampelos pareira L. (Menispermaceae)[ 144,190,202,203]


13

Table 1. Continued

Cleistopholis staudtii Engl, et Diels (Annonaceae)[147] Cyclea barbata (Wall.) Miers (Menispermaceae)[90] Cyclea barbata (Wall.) Miers (MenispermaceaeX132 or 133)[177,178] Cyclea hainanensis Merr. (Menispermaceae)(132 or 133)[175] Cyclea madagascahensis Baill. (Menispermaceae)[144] Isolona pilosa Diels (Annonaceae)[ 180,181 ] Paracyclea ochiaiana (Yamamoto) Kudo and Yamamoto (Menispermaceae)[ 182] Peruvian curare [145] Pleogyne australis Benth. (Menispermaceae)[also called Pleogyne cunninghamii Miers (Menispermaceae)][l 83] Pleogyne cunninghamii Miers (Menispermaceae)[also called Pleogyne australis Benth. (Menispermaceae)[183] Stephania epigeae Diburong (Menispermaceae)[130] 2

Cuspidaline C37H4206N2:610.3043 Limacia cuspidata Hook. f. and Thorns. (Menispermaceae)[ 184] Limacia oblonga Miers (Menispermaceae)[185]

402 Cycleabarbatine Cyclea barbata (Wall.) Miers (Menispermaceae)[90]

C37H40O6N2.608.2886

134 Cycleacurine Cyclea peltata Diels (Menispermaceae)[43]

€35*^0^2:580.2573

58

Cycleadrine Cyclea barbata (Wall.) Miers (Menispermaceae)[l] Cyclea peltata Diels (Menispermaceae)[43]

C37H40O6N2:608.2886

59

Cycleahomine Cyclea peltata Diels (Menispermaceae)[43]

C3,H4506N2+ :637.3278

286 Cycleaneonine Cyclea racemosa Oliv. (Menispermaceae)[187,188]

C3lH42O6N2:622.3043

403 (-)-Cycleaneonine Cyclea sutchuenensis Gagnep. (Menispermaceae)[ 188]

C38H42O6N2:622.3043

121 Cycleanine C3lH42O6N2:622.3043 Chondodendron tomentosum Ruiz and Pavon (Menispermaceae)[141,142] Cissampelos insularis Makino (Menispermaceae)(also called Paracyclea insularis (Makino) Kudo and Yamamoto (Menispermaceae)][131] Cissampelos pareira L. (Menispermaceae)[189,190] Cleistopholis staudtii Engl, et Diels (Annonaceae)[147]

14

P.L.Schiff,Jr. Table 1. Continued Cyclea hypoglauca (Menispermaceae)[ 191] Cyclea insularis (Makino) Diels (Menispermaceae)[192] Cyclea tonkinensis (Menispermaceae)[193] Epinetrum cordifolium Mangenot and Miege (Menispermaceae)[194] Epinetrum mangenotti Guill. and Debray (Menispermaceae)[194] Epinetrum villosum (Excell.) Troupin (Menispermaceae)[195] Heracleum wallichi (Umbelliferae)[197] lsolona hexaloba Engl. (Annonaceae)[181] Limaciopsis loangensis Engl. (Menispermaceae)[92] Paracyclea ochiaiana (Yamamoto) Kudo and Yamamoto (Menispermaceae)[182] Stephania capitata Spreng. (Menispermaceae)[204] Stephania cepharantha Hayata (Menispermaceae)[30,32,102,104,105,131] Stephania epigeae Diburong (Menispermaceae)[132] Stephania glabra (Roxb.) Miers (Menispermaceae)[205,206] Stephania pierrii Diels (Menispermaceae)[34] Stephania tetrandra S. Moore (Menispermaceae)[207J Synclisia scabrida Miers (Menispermaceae)[ 157,158,208]

232 Cycleanine N-Oxide Synclisia scabrida Miers (Menispermaceae)[158]

C38H40O7N2:636.2836

60

Cycleanorine Cyclea barbata (Wall.) Miers (Menispermaceae)[90] Cyclea peltata Diels (Menispermaceae)[43]

C37H40O6N2:608.2886

36

Cycleapeltine (Faralaotrine) Colubrina faralaotra (Rhamnaceae)[209] Cyclea barbata (Wall.) Miers (Menispermaceae)[210] Cyclea peltata Diels (Menispermaceae)[43]

C37H40O6N2.6O8.2886

404 Cycleatjehenine Cyclea atjehensis Forman (Menispermaceae)[211,212]

C37H36O6N2:604.2574

405 Cycleatjehine Cyclea atjehensis Forman (Menispermaceae)[211]

C%H34O6N2:590.2417

37

Daphnandrine C36H38O6N2:594.2730 Albertisia papuana Becc. (Menispermaceae)[10] Anisocycla cymosa Troupin (Menispermaceae)[151] Cyclea barbata (Wall.) Miers (Menispermaceae)[90] Daphnandra micrantha Benth. (Monimiaceae)[27] Doryphora aromatica Schodde (Monimiaceae)[28] Guatteria guianensis (Aublet) R.E. Fries (Annonaceae)[12]

The BisbenzyUsoquinoline Alkaloids - A Tabular Review

15

Table 1. Continued Pachygone loyaltiensis Diels (Menispermaceae)[13] Stephania erecta Craib. (Menispermaceae)[135] Stephania pierrii Diels (Menispermaceae)[34] 191 Daphnine C37H3207N2:616.2209 Daphnandra dielsii Perk. (Monimiaceae)[213] Daphnandra repandula F. Muell. (Monimiaceae)[214,215] 38

Daphnoline C35H36O6N2:580.2573 Albertisia laurifolia (Menispermaceae)[9] Albertisia papuana Becc. (Menispermaceae)[16,10] Cocculus pendulus (Forsk.) Diels (Menispermaceae)[139] Cocculus trilobus DC. (Menispermaceae)[216] Daphnandra aromatica F.M. Bailey (Monimiaceae)[26] Daphnandra micrantha Benth. (Monimiaceae)[27] Doryphora aromatica Schodde (Monimiaceae)[28] Guatteria guianensis (Aublet) R.E. Fries (Annonaceae)[12] Pachygone dasycarpa Kurz (Menispermaceae)[7] Pachygone loyaltiensis Diels (Menispermaceae)[13] Pycnarrhena longifolia (Decne. ex Miq.) Becc. (Menispermaceae)[49] Pycnarrhena ozantha Diels (Menispermaceae)[120]

406 Dauriciline Menispermum dauricum DC. (Menispermaceae)[217]

C36H40O6N2.596.2886

3

Dauricine C38H4406N2:624.3199 Cardiopetalum calophyllum Schlecht (Annonaceae)[218] Menispermum canadense L. (Menispermaceae)[219,220] Menispermum dauricum DC. (Menispermaceae)[221-228] Popowia pisocarpa (Bl.) Endl. (Annonaceae)[229]

4

Dauricinoline C37H4206N2:610.3043 Menispermum dauricum DC. (Menispermaceae)[222,223]

5

Dauricoline C36H40O6N2:596.2886 Menispermum dauricum DC. (Menispermaceae)[221,223] Popowia pisocarpa (Bl.) Endl. (Annonaceae)[229]

6

Daurinoline C37H4206N2:610.3043 Menispermum canadense L. (Menispermaceae)[220] Menispermum dauricum DC. (Menispermaceae)[221,223]

16

P.L.Schiff,Jr. Table 1. Continued

192 Daurisoline C37H4206N2:610.3043 Abuta pahni (Martius) Krukoff and Barneby (Menispermaceae)[230] Menispermum dauricum D C (Menispermaceae)[223,225,227] Polyalthia nitidissima Benth. (Annonaceae)[231 ] 287 Dehatridine Dehaasia triandra Merr. (Lauraceae)[232]

C35H32O6N2:576.2260

288 Dehatrine Beilschmiedia madang Bl. (Lauraceae)[474] Dehaasia triandra Merr. (Lauraceae)[232]

C37H3806N2.606.2730

193 1,2-Dehydroapateline C34H30O5N2:546.2155 Anisocycla cymosa Troupin (Menispermaceae)[154] Cocculus pendulus (Forsk.) Diels (Menispermaceae)[139] Daphnandra apatela Schodde (Monimiaceae)[ 11 ] Doryphora aromatica Schodde (Monimiaceae)[28] Guatteria guianensis (Aublet) R.E. Fries (Annonaceae)[ 12] Pachygone loyaltiensis Diels (Menispermaceae)[13] Stephania pierrii Diels (Menispermaceae)[34] 289 1,2-Dehydrokohatamine C35H32O6N2:576.2260 Cocculus pendulus (Forsk.) Diels (Menispermaceae)[233] 290 1,2-Dehydrokohatine C34H10O6N3:562.2104 Cocculus pendulus (Forsk.) Diels (Menispermaceae)[233] 154 1,2-Dehydromicranthine Daphnandra species unnamed (Monimiaceae)[234]

C34H30O,N2:546.2155

291 1,2-Dehydro-2-Norlimacusine C36H3606N2:592.2573 Caryomene olivascens Barneby et Krukoff (Menispermaceae)[74] 292 1,2-Dehydro-2'-Nortelobine C34H30O5N3:546.2155 Cocculus pendulus (Forsk.) Diels (Menispermaceae)[233] 194 1,2-Dehydrotelobine C35H3205N2:560.2311 Albertisia papuana Becc. (Menispermaceae)[16] Anisocycla cymosa Troupin (Menispermaceae)[154] Anisocycla jolly ana (Pierre) Diels (Menispermaceae)[235] Daphnandra apatela Schodde (Monimiaceae)[ 11 ] Guatteria guianensis (Aublet) R.E. Fries (Annonaceae)[12] Pachygone loyaltiensis Diels (Menispermaceae)[13]

The Bisbenzylisoquinoline Alkaloids - A l abalar Review

17

Table 1. Continued Stephania erecta Craib. (Menispermaceae)[135] 39

Demerarine C36H38O6N2:594.2730 Nectandra rodiei R. Schomb. (Lauraceae)[also known as Ocotea rodiei (Lauraceae)][236]

293 12-O-Demethylcoclobine C36H3606N2:592.2573 Guatteria guianensis (Aublet) R.E. Fries (Annonaceae)[12] 195 7-O-Demethylisothalicberine C36H38O6N2:594.2730 Berberis chilensis Gill, ex Hook. (Berberidaceae)[237,238] Berberis lamina (Thunb.) Billbg. (Berberidaceae)[ 18] 294 12-O-Desmethyllauberine Berberis chilensis Gill, ex Hook. (Berberidaceae)[239]

C36H38O6N2:594.2730

60a 7-O-Demethylpeinamine C35H36O6N2:580.2573 Abuta grisebachii Triana and Planchon (Menispermaceae)[240] 155 12-O-Demethyltrilobine C34H3205N2:548.2311 Anisocycla gradidieri H. Bn. (Menispermaceae)[165] Cocculus pendulus (Forsk.) Diels (Menispermaceae)(designated by the authors as nortrilobine) [153] 233 N-Desmethylcycleanine Stephania glabra (Roxb.) Miers (Menispermaceae)[206] Stephania pierrii Diels (Menispermaceae)[34]

C37H40O6N2:608.2886

7

C 37 H 42 O A N 2 :6 10.3043

N'-Desmethyldauricine Menispermum canadense L. (Menispermaceae)[220]

196 N-Desmethylthalidasine Thalictrum cultratum Wall. (Ranunculaceae)[241] Thalictrum faberi Ulbr. (Ranunculaceae)[242,243]

C38H4207N2:638.2992

80

N-Desmethylthalidezine Thalictrum podocarpum Humb. (Ranunculaceae)[244]

C37H40O7N2:624.2836

16 N-Desmethylthalistyline Thalictrum baicalense Turcz. (Ranunculaceae)[245] Thalictrum longistylum DC. (Ranunculaceae)[246] Thalictrum podocarpum Humb. (Ranunculaceae)[244]

C40H46O8N2:682.3254

18

P.L.Schlfr,Jr. Table 1. Continued

197 N-Desmethylthalrugosidine Thalictrum alpinum L. (Ranunculaceae)[247]

C37H40O7N2:624.2836

260 Dihydrosecocepharanthine Stephania sasakii Hayata (Menispermaceae)[248]

C37H3gOgN2:638.2628

295 3',4'-Dihydrostephasubine C36H3606N2:592.2573 Stephania hernandifolia (Willd.) Walp. (Menispermaceae) [also called Stephania discolor Spreng. (Menispermaceae)][249] 198 Dihydrothalictrinine C38H3809N2:666.2577 Thalictrum rochebrunianum Franc, and Sav. (Ranunculaceae)[250] 146 Dihydrowarifteine Cissampelos ovalifolia DC. (Menispermaceae)[251 ]

C36H38O6N2:594.2730

407 0,0'-Dimethylgrisabine 0^0^:638.3356 Phaeanthus vietnamensis Ban. (Menispermaceae)[252,253] 234 N,N'-Dimethyllindoldhamine[231] or 0^0^:596.2886 Guattegaumerine[254] Abuta pahni (Martius) Krukoff and Barneby (Menispermaceae)[230] Berberis stolonifera (Berberidaceae)[76] Caryomene olivascens Barneby et Krukoff (Menispermaceae)[74] Guatteria gaumeri Greenman (Annonaceae)[254] Polyalthia nitidissima Benth. (Annonaceae)[231 ] 156 N,0-Dimethylmicranthine Daphnandra micrantha Benth. (Monimiaceae)[255] Daphnandra species Dt-7 (Monimiaceae)[255] Daphnandra species unnamed (Monimiaceae)[234]

C36H360,N2:576.2624

135 0,0-Dimethylcurine Cyclea hypoglauca (Menispermaceae)[191] Guatteria megalophylla Dieis (Annonaceae)[196]

C37H40O6N2:608.2886

147 Dimethyldihydrowarifteine Cissampelos ovalifolia D C (Menispermaceae)[251]

C3gH42O6N2:622.3043

148 Dimethylwarifteine Cissampelos ovalifolia DC. (Menispermaceae)[251]

C3lH40O6N2:620.2886

the Bisbenzylisoquinoline Alkaloids - A Tabular Review

19

Table 1. Continued

114 Dinklacorine Tiliacora dinklagei Engl. (Menispermaceae)[256] Tiliacora triandra Diels (Menispermaceae)[257,258]

C36H3605N2:5 76.2624

172 Dinklageine - Undetermined Structure Stephania dinklagei Diels (Menispermaceae)[259]

C36H38O6N2:594.2730

19 Dirosine C37H4206N2:610.3043 Nectandra rodiei R. Schomb. (Lauraceae)[also known as Ocotea rodiei (Lauraceae)[236] 104 Dryadine C37H40O6N2:608.2886 Dryadodaphne novoguineensis (Perk.) A.C. Smith (Monimiaceae)[260] 105 Dryadodaphnine C36H38O6N2:594.2730 Dryadodaphne novoguineensis (Perk.) A.C. Smith (Monimiaceae)[260] 296 Efatine C38H44OgN2:656.3097 Hernandia nymphaeifolia (Presl) Kubirtzki [Biasoiettia nymphaeifolia Presl, Hernandia peltata (Meissn.)] (Hernandiaceae)[6] 199 Epinorhernandezine (Semisynthetic) C3IH4207N2:638.2992 Thalictrum rochebrunianum Franc, and Sav. (Ranunculaceae)[250] 200 Epinorthalibrunine (Semisynthetic) C38H4208N2:654.2941 Thalictrum rochebrunianum Franc, and Sav. (Ranunculaceae)[250] 40

(+)-Epistephanine C37H38O6N2:606.2730 Stephania capitata Spreng. (Menispermaceae)[261] Stephania hernandifolia (Willd.) Walp. (Menispermaceae) [also called Stephania discolor Spreng. (Menispermaceae)][249,262] Stephania japonica (Thunb.) Miers (Menispermaceae)[also called Cocculus japonicus (Menispermaceae)] [263,264] Stephania japonica (Thunb.) Miers var australis (Menispermaceae)[263,264]

41

(-)-Epistephanine Anisocycla gradidieri H. Bn. (Menispermaceae)[165]

8

Espinidine Berberis laurina (Thunb.) Billbg. (Berberidaceae)[265]

C37H38O6N2:606.2730


C36H40O6N2:596.2886

9

Espinine Berbehs chilensis Gill, ex Hook. (Berberidaceae)[239] Berberis laurina (Thunb.) Billbg. (Berberidaceae)[265]

61

Fangchinoline C37H40O6N2:608.2886 Cyclea barbata (Wall.) Miers (Menispermaceae)[266] Cyclea peltata Diels (Menispermaceae)[43,267] Daphnandra species Dt-7 (Monimiaceae)[255] Pachygone dasycarpa Kurz (Menispermaceae)[7] Stephania hernandifolia (Willd.) Walp. (Menispermaceae)[also called Stephania discolor Spreng. (Menispermaceae)] [ 199] Stephania tetrandra S. Moore (Menispermaceae)[107,207,269,270]([268] - detected, not isolated) Strychnopsis thouarsii Baill. (Menispermaceae)[271.272] Triclisia subcordata Oliv. (Menispermaceae)[ 168]

297 Fenfangjine A (Tetrandrine-2P-N-Oxide) C3gH4207N2:638.2992 Stephania tetrandra S. Moore (Menispermaceae)[207,273] 298 Fenfangjine B (Fangchinoline-2'a-N-Oxide) C37H40O7N2:624.2836 Stephania tetrandra S. Moore (Menispermaceae)[207,273] 299 Fenfangjine C (Fangchinoline-2'P-N-Oxide) C37H40O7N2:624.2836 Stephania tetrandra S. Moore (Menispermaceae)[207,273] 300 Fenfangjine D (1,3,4-Tridehydrofangchinolinium Hydroxide) C37H40O7N2:624.2836 Stephania tetrandra S. Moore (Menispermaceae)[207,274] 20

Funiferine C3gH42O6N2:622.3043 Guatteria guianensis (Aublet) R.E. Fries (Annonaceae)[ 119] Tiliacora dinklagei Engl. (Menispermaceae)[275] Tiliacora funifera Engl, ex Diels (Menispermaceae)[also known as Tiliacora warneckei Engl, ex Diels (Menispermaceae)][276]

201 Funiferine Dimethiodide C40H4gO6N2~:652.3512 (N,N-Dimethylfuniferine Iodide) Tiliacora funifera Engl, ex Diels (Menispermaceae)[also known as Tiliacora warneckei Engl, ex Diels (Menispermaceae)][277] 21

Funiferine N-Oxide C3SH4207N2:638.2992 Tiliacora funifera Engl, ex Diels (Menispermaceae)[also known as Tiliacora warneckei Engl, ex Diels (Menispermaceae)][278]

The Blsbenzyllsoqnlnoline Alkaloids - A Tabular Review

21

Table 1. Continued

301 Geraldoamine Aristolochia gigantea Mart. (Aristolochiaceae)[279]

C37H4206N2:610.3043

261 Gilgitine Berberis lycium (Royle) (Berberidaceae)[68]

C36H34OgN2:622.2316

202 Gilletine C35H3406N2:578.2417 Triclisia gilletii (DeWild.) Staner (Menispermaceae)[280,281] 302 Granjine Crematosperma sp. (Annonaceae)[ 172]

C39H4406N2:636.3199

10 Grisabine C37H4206N2:610.3043 Abuta ghsebachii Triana and Planchon (Menispermaceae)[240] Gyrocarpus americanus Jacq. (Hernandiaceae)(also known as Gyrocarpus jacquini Roxb. (Hcrnandiaceae)[282] Sciadotenia eichlericma Moldenke (Menispermaceae)[283] 303 Guattamine C37H40O6N2:608.2886 Guatteria guianensis (Aublet) R.E. Fries (Annonaceae)[l 19] 304 Guattaminone C37H36O7N2:620.2523 Guatteria guianensis (Aublet) R.E. Fries (Annonaceae)[ 119] 305 Gyroamericine C37H40O6N2:608.2886 Gyrocarpus americanus Jacq. (Hemandiaceae)[also called Gyrocarpus jacquini Roxb. (Hernandiaceae)][282] 306 Gyrocarpine C37H40O6N2:608.2886 Gyrocarpus americanus Jacq. (Hernandiaceae)[also called Gyrocarpus jacquini Roxb. (Hernandiaceae)][45,282] 307 Gyrocarpusine C37H40O6N2:608.2886 Gyrocarpus americanus Jacq. (Hernandiaceae)[also called Gyrocarpus jacquini Roxb. (Hernandiaceae)][282] 308 Gyrolidine C38H4206N2:622 3043 Gyrocarpus americanus Jacq. (Hernandiaceae)[also called Gyrocarpus jacquini Roxb. (Hernandiaceae)] [282] 136 Hayatidine Cissampelos pareira L. (Menispermaceae)[190]

C37H40O6N2:608.2886

P.L.Schifr,Jr. Table 1. Continued

137 Hayatine Cissampelos pareira L. (Menispermaceae)[ 144,190,202] Cyclea hainanensis Merr. (Menispermaceae)[175]

C36H3gO6H>:594.2730

138 Hayatinine Cissampelos pareira L. (Menispermaceae)[ 190,202]

€^0^:608.2886

81

Hernandezine (Thalicsimine) C39H4407N2:652.3149 Cocculus pendulus (Forsk.) Diels (Menispermaceae)[161] Thalictrum alpinum L. (Ranunculaceae)[284,285] Thalictrum delavayi Franch. (Ranunculaceae)[286,287] Thalictrum fendleri Engelm. ex Gray (Ranunculaceae)[288] Thalictrum flavum L. (Ranunculaceae)[289] Thalictrum foetidum L. (Ranunculaceae)[290] Thalictrum glandulosissimum (Finet et Gagnep.) W.T. Wang et S.H. Wang (Ranunculaceae)[291,292] Thalictrum hernandezii Tausch (Ranunculaceae)[293] Thalictrum lankesteri Standi. (Ranunculaceae)[294] Thalictrum podocarpum Humb. (Ranunculaceae)[244] Thalictrum rochebrunianum Franc, and Sav. (Ranunculaceae)[295] Thalictrum simplex L. (Ranunculaceae)[296] Thalictrum sultanabadense Stapf. (Ranunculaceae)[297-300]

203 Hernandezine-N-Oxide Thalictrum sultanabadense Stapf. (Ranunculaceae)[299]

C39H44O8N2:668.3098

173 Himanthine - Undetermined Structure Berberis himalaica Ahrendt (Berberidaceae)[81 ]

C37H40O6N2:608.2886

42

Homoaromoline (Homothalicrine) C37H40O6N2:608.2886 A buta splendida Krukoff and Moldenke (Menispermaceae)[ 15] Albertisia papuana Becc. (Menispermaceae)[16] Anisocycla jolly ana (Pierre) Diels (Menispermaceae)[235] Arcangelisia flava (L.) Merr. (Menispermaceae)[301] Berberis boliviano Lechl. (Berberidaceae)[18] Berberis laurina (Thunb.) Billbg. (Berberidaceae)[18] Cyclea barbata (Wall.) Miers (Menispermaceae)[210,302,303] Doryphora aromatica Schodde (Monimiaceae)[28] Pseudoxandra sclerocarpa Maas (Annonaceae)fl 17] Pycnarrhena longifolia (Decne. ex Miq.) Becc. (Menispermaceae)[49] Stephania cepharantha Hayata (Menispermaceae)[30,32,104] Stephania erecta Craib. (Menispermaceae)[134,135] Stephania excentrica H-S. Lo (Menispermaceae)[304]


23

Table 1. Continued

Thalictrum lucidum L. (Ranunculaceae)[37] Thalictrum minus L. var. microphyllum Boiss. (Ranunculaceae)[38] Thalictrum thunbergii DC. (Ranunculaceae)[40,41] The following plants yielded alkaloids that were formerly named thalrugosamine, but a reevlaution of the assignment of the structure of thalrugosamine published in 1972 [305] demonstrated an inconsistency in the structural representation (but not the actual work of the alkaloid [1,2] with the revelation that (+)-thalrugosmine was in reality (+)homoaromoline [38]: Limaciopsis loangensis Engl. (Menispermaceae)[92] Stephania pierrii Diels (Menispermaceae)[34] Stephania venosa Spreng. (Menispermaceae)[306] Thalictrum rugosum Ait. (Ranunculaceae)[also called Thalictrum glaucum Desf. (Ranunculaceae)][305] 309 5-Hydroxyapateline C34H32O6N2:564.2260 Cocculus pendulus (Forsk.) Diels (Menispermaceae)[233] 310 5-Hydroxytelobine C33H3406N2:578.2417 Cocculus pendulus (Forsk.) Diels (Menispermaceae)[233] 311 5-Hydroxythalidasine Thalictrum cultratum Wall. (Ranunculaceae)[307]

C39H44OgN2:668.3098

312 5-Hydroxythalidasine-2ot-N-Oxide Thalictrum cultratum Wall. (Ranunculaceae)[35]

C3QH44O9N2:684.3046

313 5-Hydroxythalmine Thalictrum cultratum Wall. (Ranunculaceae)[307]

C37H40O7N2:624.2836

43

Hypoepistephanine (Pseudoepistephanine) C36H3606N,:592.2573 Stephania japonica (Thunb.) Miers (Menispermaceae)[also called Cocculus japonicus DC. (Menispermaceae)][263] Stephania japonica (Thunb.) Miers var australis (Menispermaceae)[263]

169 Insulanoline C37H3gO6N2:606.2730 Cyclea hypoglauca (Menispermaceae)[308J Cyclea insularis (Makino) Diels (Menispermaceae)[192] Cyclea sutchuenensis Gagnep. (Menispermaceae)[252,309] 170 Insularine Cissampelos pareira L. (Menispermaceae)[189] Cyclea hypoglauca (Menispermaceae)[308]

24

P.L.Schifr,Jr. Table 1. Continued Cyclea insularis (Makino) Diels (Menispermaceae)[ 192] Cyclea sutchuenensis Gagnep. (Menispermaceae)[252] Paracyclea ochiaiana (Yamamoto) Kudo and Yamamoto (Menispermaceae)[182] Stephania japonica (Thunb.) Micrs (Menispermaceae)[also called Coccuius japonicus (Menispermaceae)][310] Stephania japonica (Thunb.) Miers var australis (Menispermaceae)[310]

408 Insularine-2p-N-Oxide Cyclea sutchuenensis Gagnep. (Menispermaceae)[252]

C38H40O7N2:636.2836

409 Insularine-2'P-N-Oxide Cyclea sutchuenensis Gagnep. (Menispermaceae)[252]

C38H40O7N2:636.2836

174 (-)-Isochondocurarine - Undetermined Structure Curare [311]

C3„H4406N2++:624.3199

122 Isochondodendrine (Isobebeerine) C36H3gO6N2:594.2730 Abuta candicans Rich ex DC. (Menispermaceae)[146] Chondodendron limaciifolium (Diels) Moldenke (Menispermaceae)[312] Chondodendron microphylum (Eichl.) Moldenke (Menispermaceae)[146] Chondodendron platiphyllum Miers (Menispermaceae)[ 146] Chondodendron tomentosum Ruiz and Pavon (Menispermaceae)[ 141,142] Chondendron toxicoferum (Wedd.) Kruk. et Mold. (Menispermaceae)[201] Cissampelos mucronata A. Rich. (Menispermaceae)[313] Cissampelos pareira L. (Menispermaceae)[144,189,190] Cleistopholis staudtii Engl, et Diels (Annonaceae)[147] Cyclea barbata (Wall.) Miers (Menispermaceae)[303,314] Cyclea hainanensis Merr. (Menispermaceae)[175] Cyclea insularis (Makino) Diels (Menispermaceae)[315] Cyclea madagascariensis Baill. (Menispermaceae)[144] Cyclea peltata Diels (Menispermaceae)[267] Cyclea sutchuenensis Gagnep. (Menispermaceae)[309] Epinetrum cordifolium Mangenot and Miege (Menispermaceae)[194] Epinetrum mangenotti Guill. and Debray (Menispermaceae)[194] Epinetrum villosum (Excell.) Troupin (Menispermaceae)[195] Guatteria megalophylla Diels (Annonaceae)[196] Heracleum wallichi (Umbelliferae)[197] Isolona hexaloba Engl. (Annonaceae)[181] Isolona pilosa Diels (Annonaceae)[180] Paracyclea ochiaiana (Yamamoto) Kudo and Yamamoto (Menispermaceae)[182] Pleogyne cunninghamii Miers [Pleogyne australis Benth. (Menispermaceae)][183] Sciadotenia toxifera Krukoff and A.C. Smith (Menispermaceae)[198] Stephania erecta Craib. (Menispermaceae)[130]

The Bisbenzylisoqninoline Alkaloids - A Tabular Review

25

Table 1. Continued

Stephania hernandifolia (Willd.) Walp.(Menispermaceae)[also called Stephania discolor Spreng. (Menispermaceae)][199] 410 Isocuricycleatjenine Cyclea atjehensis Forman (Menispermaceae)[174]

C39H4606N2:634.2679

411 Isocuricycleatjine Cyclea atjehensis Forman (Menispermaceae)[174]

C37H36O7N2:620.2523

412 Isocycleaneonine Cyclea sutchuenensis Gagnep. (Menispermaceae)[188]

C38H42O6N2:622.3043

235 Isodaurisoline Polyalthia nitidissima Benth. (Annonaceae)[231 ]

C37H4206N2:610.3043

204 Isogilletine-N-Oxide C35H3407N2:594.2366 Triclisia gilletii (DeWild.) Staner (Menispermaceae)[281] 28

Isoliensinine Nelumbo nucifera Gaertn. (Nymphaceae)[316,317]

C37H4206N2:610.3043

87

Isotenuipine Daphnandra species (Monimiaceae)[318]

C38H40O7N2:636.2836

62

Isotetrandrine C38H42O6N2:622.3043 Atherosperma moschatum L. (Monimiaceae)[51] Berberis boliviano Lechl. (Berberidaceae)[ 18] Berberis brandisiana Ahrendt (Berberidaceae)[58] Berberis bumeliaefolia Schneid. (Berberidaceae)[ 18] Berberis cretica L. (Berberidaceae)[19] Berberis empetrifolia (Berberidaceae)[319] Berberis heteropoda Schrenk (Berberidaceae)[see Berberis vulgaris L. (Berberidaceae)][112] Berberis kawakamii Hayata (Berberidaceae)[64] Berberis koreana Palib. (Berberidaceae)[320] Berberis mingetsensis Hayata (Berberidaceae)[69] Berberis morrisonensis Hayata (Berberidaceae)[69] Berberis nummularia Bge. (Berberidaceae)[21,321 ] Berberis paucidentata Rusby. (Berberidaceae)f 18] Berberis poiretii (Berberidaceae)[72] Berberis stolonifera (Berberidaceae)[23] Berberis thunbergii D C (Berberidaceae)[79,80] Berberis valdiviana (Berberidaceae)[322]

26

P.L.Schiff,Jr. Table 1. Continued Berberis wilsoniae Hemsl. et Wils. (Berberidacaeae)[87] Cocculus pendulus (Forsk.) Diels (Menispermaceae)[153] Cyclea barbata (Wall.) Miers (Menispermaceae)[302] Doryphora aromatica Schodde (Monimiaceae)[28] Gyrocarpus americanus Jacq. (Hernandiaceae)[also called Gyrocarpus jacquini Roxb. (Hernandiaceae)][282] Isopyrum thalictroides L. (Ranunculaceae)[91,323] Laurelia sempervirens R. et P. (Monimiaceae)[324,325] Limaciopsis loangensis Engl. (Menispermaceae)[92] Mahonia aquifolium (Pursh) Nutt. (Berberidaceae)[29,95] Mahonia japonica DC. (Berberidaceae)[55,326] Mahonia lomariifolia Takeda (Berberidaceae)[97] Mahonia morrisonensis Takeda (Berberidaceae)[97] Mahonia philippinensis Takeda (Berberidaceae)[98] Mahonia siamensis Takeda (Berberidaceae)[327] Pycnarrhena australiana F. Muell. (Menispermaceae)[99] Pycnarrhena manillensis F. Muell. or Vidal (Menispermaceae)[100,101] Stephania cepharantha Hayata (Menispermaceae)[30,32,103,104] Stephania erecta Craib. (Menispermaceae)[135] Stephania pierrii Diels (Menispermaceae)[34] Stephania tetrandra S. Moore (Menispermaceae)[269] Thalictrum foetidum L. (Ranunculaceae)[108] Tiliacora funifera Engl, ex Diels (Menispermaceae)[328] Triclisia gilletii (DeWild.) Staner (Menispermaceae)[168]

205 Isothalicberine C37H40O6N2:608.2886 Berberis chilensis Gill, ex Hook. (Berberidaceae)[237,238] 82

Isothalidezine C3IH4207N2:638.2992 Thalictrum delavayi Franch. (Ranunculaceae)[286] Thalictrum glandulosissimum (Finet et Gagnep.) W.T. Wang et S.H. Wang (Ranunculaceae)[292] Thalictrum podocarpum Humb. (Ranunculaceae)[244]

157 Isotrilobine (Homotrilobine) C36H3605N2:576.2624 Albertisia papuana Becc. (Menispermaceae)[16] Anisocycla jollyana (Pierre) Diels (Menispermaceae)[235] Cocculus hirsutus Diels (Menispermaceae)[329-331] Cocculus laurifolius DC.. (Menispermaccae)[329] Cocculus pendulus (Forsk.) Diels (Menispermaceae)[139,153] Cocculus sarmentosus Diels (Menispcrmaceae)[332] Cocculus trilobus DC. (Menispermaceae)[216,333] Pachygone dasycarpa Kurz (Menispermaceae)[7]

The BlsbenzylftsoqnlnoUne Alkaloids - A Tabular Review

27

Table 1. Continued Pachygone loyaltiensis Diels (Menispermaceae)[13] Pachygone pubescens Benth. (Menispermaceae)[334] Stephania hernandifolia (Willd.) WaIp.(Menispermaceae)[also called Stephania discolor Spreng. (Menispermaceae)][335] 262 Jhelumine Berberis lycium (Royle) (Berberidaceae)[138]

C36H3807N2:610.2679

206 Johnsonine Daphnandra johnsonii Schodde (Monimiaceae)[336]

C37H40O6N2:608.2886

314 Kohatamine C35H3406N2:578.2417 Cocculus pendulus (Forsk.) Diels (Menispermaceae)[233] 236 Kohatine C34H32O6N2:564.2260 Cocculus pendulus (Forsk.) Diels (Menispermaceae)[ 139,233] 63

Krukovine C36H3gO6N2:594.2730 Abuta splendida Krukoff and Moldenke (Menispermaceae)[15] Curarea candicans (L.C. Rich) Barneby and Krukoff (Menispermaceae)[ 127,128] Pycnarrhena longifolia (Decne. ex Miq.) Becc. (Menispermaceae)[49]

237 Kurramine C33H2805N2:532.1998 Cocculus pendulus (Forsk.) Diels (Menispermaceae)[139] 106 Lauberine C37H40O6N2:608.2886 Berberis laurina (Thunb.) Billbg. (Berberidaceae)[ 18,337] C37H4206N2:610.3043

29

Liensinine Nelumbo nucifera Gaertn. (Nymphaceae)[338-341]

64

Limacine ^7^0^:608.2886 Anisocycla jollyana (Pierre) Diels (Menispermaceae)[235] Arcangelisia flava (L.) Merr. (Menispermaceae)[301] Colubrina faralaotra (Rhamnaceae)[209] Curarea candicans (L.C. Rich) Barneby and Krukoff (Menispermaceae)[ 127,128] Cyclea barbata (Wall.) Miers (Menispermaceae)[89,210) Gyrocarpus americanus Jacq. (Hernandiaceae)[also called Gyrocarpus jacquini Roxb. (Hernandiaceae)][45,282] Limacia cuspidata Hook. f. and Thoms. (Menispermaceae)[ 184] Limacia oblonga Miers (Menispexmaceae)[185] Phaeanthus crassipetalus Becc. (Menispermaceae)[342]

28

P.L.SchiiT,Jr. Table 1. Continued Pycnarrhena longifolia (Decne. ex Miq.) Becc. (Menispermaceae)[49] Pycnarrhena novoguineensis Miq. (Menispermaceae)[22] Spirospermum penduliflorum Thou. (Menispermaceae)[271,272]

315 Limacine-2'ct-N-Oxide Curarea candicans (L.C. Rich) Barneby and Kmkoff (Menispermaceae)[ 127-129]

C37H40O7N2:624.2836

316 Limacine-2p-N-Oxide Curarea candicans (L.C. Rich) Barneby and Kmkoff (Menispermaceae)[ 127-129]

C37H40O7N2:624.2836

317 Limacine-2'P-N-Oxide C37H40O7N2:624.2836 Anisocycla jollyana (Pierre) Diels (Menispermaceae)[235] Curarea candicans (L.C. Rich) Barneby and Krukoff (Menispermaceae)[ 127-129] 44

Limacusine C37H40O6N2:608.2886 Curarea candicans (L.C. Rich) Barneby and Krukoff (Menispermaceae)[ 127-129] Limacia cuspidata Hook. f. and Thorns. (Menispermaceae)[ 184] Limacia oblonga Miers (Menispermaceae)[185]

413 Limacusine-2'P-N-Oxide C37H40O7N2:624.2836 Anisocycla jollyana (Pierre) Diels (Menispermaceae)[235] 11

Lindoldhamine C34H3606N2:568.2573 Abuta pahni (Martius) Krukoff and Barneby (Menispermaceae)[230] Albertisia papuana Becc. (Menispermaceae)[10,16] Lindera oldhamii Hemsl. (Lauraceae)[343] Polyalthia nitidissima Benth. (Annonaceae)[231 ]

44a Macolidine C36H3gO6N2:594.2730 Abuta grisebachii Triana and Planchon (Menispermaceae)[240] 44b Macoline C37H4206N2:610.3043 Abuta grisebachii Triana and Planchon (Menispermaceae)[240] 15

Magnolamine C37H4207N2:626.2992 Magnolia fuscata Andr. (Magnoliaceae)[344][also known as Michelia fuscata Blume (Magnoliaceae)]

The Bisbenzyllsoquinoline Alkaloids - A Tabular Review

29

Table 1. Continued 12 Magnoline (Grisabutine) C36H40O6N2:596.2886 Abuta grisebachii Triana and Planchon (Menispermaceae)[240] Magnolia fuscata Andr. (Magnoliaceae)[344](also known as Michelia fuscata Blume (Magnoliaceae)[475]) 238 Malekulatine C39H46O8N2:670.3254 Hernandia peltata Meissn. (Hernandiaceae)[345) Hernandia sonora L. (H. ovigera L.)(Hernandiaceae)[346,347] 391 Maroumine C37H3gOgN2:638.2628 Gyrocarpus americanus Jacq. (Hernandiaceae)[also called Gyrocarpus jacquini Roxb. (Hernandiaceae)][45] 318 Medelline Pseudoxandra aff. lucida Fries (Annonaceae)[348]

C37H38O6N2:606.2730

165 Menisarine Cocculus leaebe DC. (Menispermaceae)[349] Cocculus sarmentosus Diels (Menispermaceae)[332]

C36H3406N2:590.2417

65

Menisidine Stephania tetrandra S. Moore (Menispermaceae)[350]

C37H40O6N2:608.2886

66

Menisine Stephania tetrandra S. Moore (Menispermaceae)[350]

C37H40O6N2:608.2886

207 N-Methylapateline Daphnandra johnsonii Schodde (Monimiaceae)[336]

C35H3405N2:562.2468

66a 2-N#-Methylberbamine Berberis oblonga (Regl.)(Berberidaceae)[351,352] Berberis turcomanica Kar. (Berberidaceae)f 116]

C38H4306N2*:623.3121

239 O-Methylcocsoline Albertisia papuana Becc. (Menispermaceae)[10,16] Pachygone loyaltiensis Diels (Menispermaceae)[13]

C35H3405N2:562.2468

414 12-0-Methylcocsoline-2'p-N-Oxide Anisocycla cymosa Troupin (Menispermaceae)[ 159]

C35H3406N2:578.2417

415 O-Methylcocsulinine C36H3606N2:592.2573 Cocculus pendulus (Forsk.) Diels (Menispermaceae)[153]

30


139 4"-0-Methylcurine Cissampelos pareira L. (Menispermaceae)[203] Cyclea hainanensis Merr. (Menispermaceae)[175]

C37H40O6N2:608.2886

140 12'-OMethylcurine Guatteria megalophylla Diels (Annonaceae)[ 196]

C37H40O6N2:608.2886

240 7'-0-Methylcuspidaline Aristolochia elegans (Aristolochiaceae)[353]

C3gH4406N2:624.3199

12a O-Methyldauricine Colubrina asiatica Brogn. (Rhamnaceae)[354] Popowia pisocarpa (Bl.) Endl. (Annonaceae)[229]

C39H4606N2:638.3356

263 O-Methyldeoxopunjabine Stephania sasakii Hayata (Menispermaceae)[248]

C3AH3606N2:592.2573

66b N-Methyl-7-O-Demethylpeinamine C36H3gO6N2:594.2730 Abuta grisebachii Triana and Planchon (Menispermaceae)[240] Pachygone dasycarpa Kurz (Menispermaceae)[7] 149 Methyldihydrowarifteine Cissampelos ovalifolia DC. (Menispermaceae)[251 ]

C37H40O6N2:608.2886

416 2-N-Methylfangchinoline Stephania tetrandra S. Moore (Menispermaceae)[355]

C3gH43OftN2+:623.3121

417 7-O-Methylgrisabine Phaeanthus vietnamensis Ban. (Menispermaceae)[252]

C3gH4406N2:624.3199

319 N-2r-Methylisotetrandrine Berberis oblonga (RegI.)(Berberidaceae)[70J

C39H4506N2*:637.3278

94

O-Methylisothalicberine C3gH42O6N2:622.3043 Berberis chilensis Gill, ex Hook. (Berberidaceae)[237] Berberis laurina (Thunb.) Billbg. (Berberidaceae)[48,337]

320 O-Methyllimacusine C3gH42O6N2:622.3043 Gyrocarpus americanus Jacq. (Hernandiaceae)[also called Gyrocarpus jacquini Roxb. (Hernandiaceae)][282] 321 2-N-Methyllindoldhamine C35H3gO6N2:582.2730 Abuta pahni (Martius) Krukoff and Barneby (Menispermaceae)[230]

The Blsbenzyllsoquinoline Alkaloids - A Tabular Review

31

Table 1. Continued 322 2'-N-MethyllindoIdhamine C35H38O6N2:582.2730 Abuta pahni (Martius) Krukoff and Barneby (Menispermaceae)[230] 241 7-O-MethylIindoldhamine Polyalthia nitidissima Benth. (Annonaceae)[231 ]

C35H38O6N2:582.2730

242 7-O-Methyllindoldhamine Polyalthia nitidissima Benth. (Annonaceae)[231 ]

C35H38O6N2:582.2730

158 O-Methylmicranthine Daphnandra micrantha Benth. (Monimiaceae)[255] Daphnandra species Dt-7 (Monimiaceae)[255] Daphnandra species unnamed (Monimiaceae)[234]

C35H3405N2:562.2468

208 N-Methylnorapateline Daphnandra johnsonii Schodde (Monimiaceae)[336]

C34H3205N2:548.2311

243 N-Methylpachygonamine C3368,371,379] Thalictrum minus L. var. minus (Ranunculaceae)[375] Thalictrum revolutum DC. (Ranunculaceae)[376]

C37H38O6N2:606.2730

244 O-Methylthalmine Thalictrum cultratum Wall. (Ranunculaceae)[307] Thalictrum sultanabadense Stapf. (Ranunculaceac)[380]

C38H42O6N2:622.3043

96

323 N-Methyltiliamosine C37H38O6N2:606.2730 Tiliacora racemosa Colebr. (Menispermaceae)[also called Tiliacora acuminata (Lam.) Miers (Menispermaceae)][381,382] 419 12-O-Methyltricordatine Pachygone dasycarpa Kurz (Menispermaceae)[7]

C35H3405N2:562.2468

150 Methylwarifteine Cissampelos ovalifolia DC. (Menispermaceae)[251 ]

C37H38O6N2:606.2730

ThetilisbenzylisoquinolineAlkaloids - A Tabular Review

33

Table 1. Continued

159 Micranthine Daphnandra micrantha Benth. (Monimiaceae)[27,255] Daphnandra species unnamed (Monimiaceae)[234]

C34H3205N,:548.2311

67

C39H4506N/:637.3278

Monomethyltetrandrinium Cyclea barbata (Wall.) Miers (Menispermaceae)[383]

324 Monterine Crematosperma sp. (Annonaceae)[172]

C38H42O6N2:622.3043

30

C38H4406N2:624.3199

Neferine Nelumbo nucifera Gaertn. (Nymphaceae)[317,339]

111 Nemuarine Nemuaron vieillardi Baill. (Monimiaceae)[384]

C37H40O6N2:608.2886

175 (+)-Neochondocurarine - Undetermined Structure Curare [311]

C38H4406N2":624.3199

123 Neoprotocuridine Curare [1]

C3AH38O6N::594.2730

420 Neosutchuenenine Cyclea sutchuenensis Gagnep. (Menispermaceae)[309]

C36H40O6N2:596.2886

211 Neothalibrine C38H4406N2:624.3199 Thalictrum alpinum L. (Ranunculaceae)[247] Thalictrum cultratum Wall. (Ranunculaceae)[35] Thalictrum revolutum DC. (Ranunculaceae)[377] Thalictrum rugosum Ait. (Ranunculaceae)[also called Thalictrum glaucum Desf. (Ranunculaceae)][39] 325 Neothalibrine-2'a-N-Oxide Thalictrum cultratum Wall. (Ranunculaceae)[35] 68

C3gH44O7N2:640.3149

2-N-Norberbamine C36H3gO6N2:594.2730 Cocculus pendulus (Forsk.) Diels (Menispermaceae)[ 139] Pycnarrhena australiana F. Muell. (Menispermaceae)[99] Pycnarrhena ozantha Diels (Menispermaceae)[120] Stephania pierrii Diels (Menispermaceae)[34]

326 2-Norcepharanoline Stephania pierrii Diels (Menispermaceae)[34]

C35H3406N2:578.2417

34


327 2-Norcepharanthine Stephania erecta Craib. (Menispermaceae)[ 135] Stephania suberosa Forman (Menispermaceae)[137]

C36H3606N2:592.2573

328 2'-Norcepharanthine Stephania pierrii Diels (Menispermaceae)[34)

C36H3606N2:592.2573

230 Nor-Nb-Chondrocurine Peruvian curare [145]

C35H3AO6N2:580.2573

421 2'-Norcocsoline Anisocycla cymosa Troupin (Menispermaceae)[159]

C33H30O5N,:534.2155

329 2'-Norcocsuline Albertisia papuana Becc. (Menispermaceae)[ 10] Pachygone dasycarpa Kurz (Menispermaceae)[7]

C34H3205N2:548.2311

422 N-Norcocsulinine C34H32O6N2:564.2260 Cocculus pendulus (Forsk.) Diels (Menispennaceae)[153] 124 (+)-Norcycleanine C37H40O6N2:608.2886 Chondodendron limaciifolium (Diels) Moldenke (Menispermaceae)[ 141,312] Chondodendron tomentosum Ruiz and Pavon (Menispermaceae)[141] Cyclea insularis (Makino) Diels (Menispermaceae)[ 192] Epinetrum villosum (Excell.) Troupin (Menispermaceae)[195] Sync Iis ia scabrida Miers (Menispermaceae)[158] 125 (-)-Norcycleanine Isolona hexaloba Engl. (Annonaceae)[181] Stephania cepharantha Hayata (Menispermaceae)[32]

C37H40O6N2:608.2886

330 2'-Nordaurisoline C36H40O6N2:596.2886 Abuta pahni (Martius) KrukofT and Barneby (Menispermaceae)[230] 331 2'-Norfuniferine C37H40O6N2:608.2886 Guatteria guianensis (Aublet) R.E. Fries (Annonaceae)fl 19] 332 2'-Norguattaguianine C37H40O6N2:608.2886 Guatteria guianensis (Aublet) R.E. Fries (Annonaceae)[l 19] 212 N'-Norhernandezine C38H4207N2:638.2992 Thalictrum rochebrunianum Franc, and Sav. (Ranunculaceae)[250]

The Bisbenzylisoqainoline Alkaloids - A Tabular Review

35

Table 1. Continued 333 2-Norisocepharanthine Stephania pierrii Diels (Menispermaceae)[34]

C36H3606N2:592.2573

334 2-Norisotetrandrine Stephania erecta Craib. (Menispermaceae)[135] Stephania pierrii Diels (Menispermaceae)[34]

C37H40O6N2:608.2886

213 Nor-2'-Isotetrandrine Limaciopsis loangensis Engl. (Menispermaceae)[92] Stephania pierrii Diels (Menispermaceae)[34]

C37H40O6N2:608.2886

335 Norisoyanangine Tiliacora triandra Diels (Menispermaceae)[385]

C35H3406N2:578.2417

336 2-Norlimacine C36H38O6N2:594.2730 Anisocycla jolly ana (Pierre) Diels (Menispermaceae)[235] Caryomene olivascens Barneby et KrukofT (Menispermaceae)[74] 423 2'-Norlimacine C36H3gO6N2:594.2730 Anisocycla jollyana (Pierre) Diels (Menispermaceae)[235] Cyclea barbata (Wall.) Miers (Menispermaceae)[90] 245 2-Norlimacusine C3AH3RO6N2:594.2730 Caryomene olivascens Barneby et KrukofT (Menispermaceae)[74] Sciadotenia eichleriana Moldenke (Menispermaceae)[283] 166 Normenisarine Cocculus trilobus DC. (Menispermaceae)[216]

C33H32O6N2:576.2260

337 2'-Norobaberine Stephania pierrii Diels (Menispermaceae)[34J

C37H40O6N2:608.2886

424 2-Norobaberine-2'p-N-Oxide Anisocycla cymosa Troupin (Menispermaceae)[151]

C37H40O7N2:624.2836

69

2-N-Norobamegine C35H36O6N2:580.2573 Pycnarrhena australiana F. Muell. (Menispermaceae)[99] Pycnarrhena ozantha Diels (Menispermaceae)[l 18,120]

338 2'-Noroxyacanthine Thalictrum cultratum Wall. (Ranunculaceae)[35]

C36H3SO6N2:594.2730

36


109 Norpanurensine A buta panurensis Eichl. (Menispermaceae)[386]

C36H3806N2:594.2730

246 Norpenduline C36H38O6N2:594.2730 Cocculus pendulus (Forsk.) Diels (Menispermaceae)[139] 339 2'-Norpisopowiaridine Popowia pisocarpa (Bl.) Endl. (Annonaceae)[229]

C36H40O6N2:596.2886

22 Norrodiasine C37H40O6N2:608.2886 Nectandra rodiei R. Schomb. (Lauraceae)[also known as Ocotea rodiei (Lauraceae)][236] 340 Norstephasubine Stephania suberosa Forman (Menispermaceae)[137]

C35H32O6N2:576.2260

88

(+)-Nortenuipine Daphrtandra johnsonii Schodde (Monimiaceae)[336] Daphnandra species Dt-7 (Monimiaceae)[255] Daphnandra tenuipes Perk. (Monimiaceae)[387]

C37H3g07N2:622.2679

89

(-)-Nortenuipine Daphnandra tenuipes Perk. (Monimiaceae)[27,387]

C37I l3807N2:622.2679

70

2-Nortetrandrine C37H40O6N2:608.2886 Nectandra rodiei R. Schomb. (Lauraceae)[also known as Ocotea rodiei][388]

13 Northalibrine C37H4206N2:610.3043 Thalictrum rochebrunianum Franc, and Sav. (Ranunculaceae)[389] 341 Northalibroline Thalictrum minus L. var. minus (Ranunculaceae)[390]

C35H38O6N2:582.2730

214 N'-Northalibrunine C38H4208N2:654.2941 Thalictrum rochebrunianum Franc, and Sav. (Ranunculaceae)[250,361] 342 2'-Northaliphylline Thalictrum cultratum Wall. (Ranunculaceae)[35,307]

C36H3806N2:594.2730

343 2-Northalmine Thalictrum cultratum Wall. (Ranunculaceae)[241]

C36H38O6N2:594.2730


37

Table 1. Continued

344 2-Northalrugosine Pycnarrhena ozantha Diels (Menispermaceae)[ 120] Stephania erecta Craib. (Menispermaceae)[135]

C36H38O6N2:594.2730

115 Nortiliacorine A (Isotiliarine) C35H340,N2:562.2468 Tiliacora funifera Engl, ex Diels (Menispermaceae)falso called Tiliacora warneckei Engl, ex Diels (Menispermaceae)][391] Tiliacora triandra Diels (Menispermaceae)[385] 116 Nortiliacorinine A (Pseudotiliarine) C35H3405N2:562.2468 Tiliacora dinklagei Engl. (Menispermaceae)[275] Tiliacora fumfera Engl, ex Diels (Menispermaceae)[also called Tiliacora warneckei Engl, ex Diels (Menispermaceae)][391] Tiliacora racemosa Colebr. (Menispermaceae)[also called Tiliacora acuminata (Lam.) Miers (Menispermaceae)][392-396] Tiliacora triandra Diels (Menispermaceae)[257,397.398] 117 Nortiliacorinine B C35H3405N2:562.2468 Tiliacora racemosa Colebr. (Menispermaceae)[also called Tiliacora acuminata (Lam.) Miers (Menispermaceae)][393] 345 2'-Nortiliageine C3ftH3RO6N2:594.2730 Guatteria guianensis (Aublet) R.E. Fries (Annonaceae)[ 119] 247 Nortrilobine (Bisnortrilobine) C34H320,N2:548.2311 Pachygone ovata (Poir.) Miers ex Hook (Menispermaceae)[399] 346 Noryanangine Tiliacora triandra Diels (Menispermaceae)[385]

C3,H3406N2:578.2417

46

C38H42O6N2:622.3043

Obaberine Albertisia papuana Becc. (Menispermaceae)[16] Berberis boliviano Lechl. (Berberidaceae)[ 18] Berberis cretica L. (Berberidaceae)[19] Berberis heterobotrys Wolf. (Berberidaceae)[60] Berberis iliensis (Berberidaceae)[62] Berberis koreana Palib. (Berberidaceae)[320] Berberis laurina (Thunb.) Billbg. (Berberidaceae)[337] Berberis paucidentata Rusby. (Berberidaceae)[18] Berberis pseudambalata (Berberidaceae)[230] Berberis tschonoskyana Regel (Berberidaceae)[400] Berberis vatdiviana (Berberidaceae)[322] Dehaasia triandra Merr. (Lauraceae)[232,401]

P.L.Schiff,Jr. Table 1. Continued Laurelia sempervirens R. et P. (Monimiaceae)[402] Mahonia repens (Lindl.) G. Don (Berberidaceae)[403] Pseudoxandra aff. lucida Fries (Annonaceae)[8] Pycnarrhena longifolia (Decne. ex Miq.) Becc. (Menispermaceae)[49] Stephania erecta Craib. (Menispermaceae)[135] Stephania pierrii Diels (Menispermaceae)[34] Stephania sasakii Hayata (Menispermaceae)[248] Thalictrum cultratum Wall. (Ranunculaceae)[35] Thalictrum lucidum L. (Ranunculaceae)[37] Thalictrum minus L. (Ranunculaceae)[404] Thalictrum minus L. var. majus (Ranunculaceae)[373J Thalictrum minus L. var. microphyllum Boiss. (Ranunculaceae)[374] Thalictrum rugosum Ait. (Ranunculaceae)[also called Thalictrum glaucum Desf. (Ranunculaceae)][39] 71

Obamegine C36H3g06N2:594.2730 Berberis boliviano Lechl. (Berberidaceae)[ 18] Berberis cretica L. (Berberidaceae)[19] Berberis tschonoskyana Regel (Berberidaceae)[400] Mahonia aquifolium (Pursh) Nutt. (Berberidaceae)[29] Mahonia repens (Lindl.) G. Don (Berberidaceae)[403] Stephania cepharantha Hayata (Menispermaceae)[32] Stephania japonica (Thunb.) Miers (Menispermaceae)(also called Cocculus japonic us D C (Menispermaceae)[405] Thalictrum lucidum L. (Ranunculaceae)[37] Thalictrum minus L. var. microphyllum Boiss. (Ranunculaceae)[38] Thalictrum rugosum Ait. (Ranunculaceae)[406] Triclisia gilletii (DeWild.) Staner (Menipspermaceae)[281] Xanthorrhiza simplicissima Marsh (Ranunculaceae)[407]

47

Oblongamine Berberis oblonga (Regl.)(Berberidaceae)[l 15]

C38H4306N2*:623.3121

176 Ocodemerine - Undetermined Structure C37H4o06N2:608.2886 Nectandra rodiei R. Schomb. (Lauraceae)[also known as Ocotea rodiei (Lauraceae)][236] 23 Ocotine C37H4o06N2:608.2886 Nectandra rodiei R. Schomb. (Lauraceae)[also known as Ocotea rodiei (Lauraceae)][388] 24

Ocotosine C37H3lO6N2:606.2730 Nectandra rodiei R. Schomb. (Lauraceae)[also known as Ocotea rodiei (Lauraceae)][388]


39

Table 1. Continued

248 Osornine Berbehs buxifolia Lam. (Berberidaceae)[123]

C38H4207N2:638.2992

177 Otocamine - Undetermined Structure C37H40O6N2:608.2886 Nectandra rodiei R. Schomb. (Lauraceae)[also known as Ocotea rodiei (Lauraceae)][236] 347 Oxandrine Pseudoxandra aff. lucida Fries (Annonaceae)[408]

C37H3807N2:622.2679

348 Oxandrinine Pseudoxandra aff. lucida Fries (Annonaceae)[408]

C38H40O7N2:636.2836

47a Oxoepistephanine C37H36O7N2:620.2523 Stephania hernandifolia (Willd.) Walp. (Menispermaceae)[also called Stephania discolor Spreng. (Menispermaceae)[409] 349 Oxofangchirine Stephania tetrandra S. Moore (Menispermaceae)[410]

C37H3:616.2573 Phaeanthus ebracteolatus (Presl) Merill. (Menispermaceae)[162,163]

74

Phaeanthine C3gH42O6N2:622.3043 Cyclea burmanni (DC.) Miers ex. Hook. f. & Thorns. (Menispermaceae)[164] Gyrocarpus americanus Jacq. (Hernandiaceae)[also called Gyrocarpus jacquini Roxb. (Hernandiaceae)][45,282,422] Phaeanthus crassipetalus Becc. (Menispermaceae)[342] Phaeanthus ebracteolatus (Presl) Merill. (Menispermaceae)[423] Pycnarrhena australiana F. Muell. (Menispermaceae)[99] Pycnarrhena manillensis F. Muell. (Menispermaceae) or Vidal (Menispermaceae)[ 100,101 ]

42


Pycnarrhena novoguineensis Miq. (Menispermaceae)[22] Triclisia patens Oliv. (Menispermaceae)[ 168,424] 356 Phaeanthine-2'a-N-Oxide C3gH4207N2:638.2992 Pycnarrhena manillensis F. Muell. (Menispermaceae) or Vidal (Menispermaceae)[ 101] 25

Phlebicine C37H40O6N2:608.2886 Crematosperma polyphlebum (Diels) Fries (Annonaceae)[425]

357 Pisopowamine Popowia pisocarpa (BI.) Endl. (Annonaceae)[229]

C37H4206N2:610.3043

358 Pisopowetine Popowia pisocarpa (Bl.) Endl. (Annonaceae)[229]

C3gH4406N2:624.3199

359 Pisopowiaridine Popowia pisocarpa (Bl.) Endl. (Annonaceae)[229]

C37H4206N2:610.3043

360 Pisopowiarine Popowia pisocarpa (Bl.) Endl. (Annonaceae)[229]

C3iH4406N2:624.3199

361 Pisopowidine Popowia pisocarpa (Bl.) Endl. (Annonaceae)[229]

C3QH4606N2:638.3359

362 Pisopowine Popowia pisocarpa (Bl.) Endl. (Annonaceae)[229]

0^^0^2:652.3512

363 Popidine Popowia pisocarpa (Bl.) Endl. (Annonaceae)[229]

C38H4406N2:624.3199

364 Popisidine Popowia pisocarpa (Bl.) Endl. (Annonaceae)[229]

C38H4406N2:624.3199

365 Popisine Popowia pisocarpa (Bl.) Endl. (Annonaceae)[229]

C38H4406N2:624.3199

366 Popisonine Popowia pisocarpa (Bl.) Endl. (Annonaceae)[229]

C37H4206N2:610.3043

367 Popisopine Popowia pisocarpa (Bl.) Endl. (Annonaceae)[229]

C37H4206N2:610.3043


43

Table 1. Continued

180 Protochondocurarine - Undetermined Structure Curare [311]

C37H4IO6N/:609.3042

126 Protocuridine Curare [1]

C36H38O6N2:594.2730

167 Pseudorepanduline Daphnandra dielsii Perk. (Monimiaceae)[234] Daphnandra species unnamed (Monimiaceae)[234]

C37H38O6N2:606.2730

368 Pseudoxandrine Pseudoxandra aff. lucida Fries (Annonaceae)[408]

C37H3807N2:622.2679

369 Pseudoxandrinine Pseudoxandra aff. lucida Fries (Annonaceae)[408]

C3gH40O7N2:636.2836

265 Punjabine Berberis lycium (Royle) (Berberidaceae)[68]

C35H32O7N2:592.2210

392 Pycmanilline C38H40O,N2:668.2734 Pycnarrhena manillensis F. Muell. (Menispermaceae) or Vidal (Meni sperm aceae)[ 101] 75

Pycnamine C37H40O6N2:608.2886 Gyrocarpus americanus Jacq. (Hernandiaceae)[also called Gyrocarpus jacquini Roxb. (Hernandiaceae)][422] Pycnarrhena manillensis F. Muell. (Menispermaceae) or Vidal (Menispermaceae)f 100,101 ] Pycnarrhena novoguineensis Miq. (Menispermaceae)[22] Triclisia patens Oliv. (Menispermaceae)[168]

181 Pycnarrhenamine - Undetermined Structure C35H40O9N2:632.2734 Pycnarrhena manillensis F. Muell. (Menispermaceae) or Vidal (Menispermaceae)[100] 182 Pycnarrhenine - Undetermined Structure C36H42O9N2:646.2890 Pycnarrhena manillensis F. Muell. (Menispermaceae) or Vidal (Menispermaceae)[100] 370 Pycnazanthine Pycnarrhena ozantha Diels (Mensispermaceae)[120]

44


49

Repandine Cyclea barbata (Wall.) Miers (Menispermaceae)[90] Daphnandra johnsonii Schodde (Monimiaceae)[336] Daphnandra repandula F. Muell. (Monimiaceae)[426]

C37H40O6N2:608.2886

90

Repandinine Daphnandra dielsii Perk. (Monimiaceae)[27] Daphnandra johnsonii Schodde (Monimiaceae)[336] Daphnandra repandula F. Muell. (Monimiaceae)[27] Daphnandra tenuipes Perk. (Monimiaceae)[387]

C38H40O7N2:636.2836

168 Repanduline C37H36O7N2:620.2523 Daphnandra dielsii Perk. (Monimiaceae)[27] Daphnandra repandula F. Muell. (Monimiaceae)[27,426] Daphnandra tenuipes Perk. (Monimiaceae)[27] 266 Revolutinone Thalictrum revolutum DC. (Ranunculaceae)[427] 26

C3gH40OJ,N2:652.2785

Rodiasine C3gH42O6N2:622.3043 Nectandra rodiei R. Schomb. (Lauraceae)[also known as Ocotea rodiei (Lauraceae)][236,388]

127 Sciadenine C37H40OAN2:608.2886 Sciadotenia toxifera Krukoff and A.C. Smith (Menispermaceae)[ 198,428] 217 Sciadoferine C36H3606N2:592.2573 Sciadotenia toxifera Krukoff and A.C. Smith (Menispermaceae)[198] 128 Sciadoline C36H34O6N2:590.2417 Sciadotenia toxifera Krukoff and A.C. Smith (Menispermaceae)[ 198,429] 267 Secantioquine Pseudoxandra aff. lucida Fries (Annonaceae)[8,430]

C37H3gO,N2:638.2628

268 Secocepharanthine Stephania sasakii Hayata (Menispermaceae)[248]

C37H36OgN2:636.2472

432 Secohomoaromoline Anisocycla jolly ana Diels (Menispermaceae)[358]

C37H3lOlN2:638.2628

431 Secoisotetrandrine Laurelia sempervirens R. et P. (Monimiaceae)[325]

C38H40OlN2:652.2785

The Bisbeuzyllsoqulnoline Alkaloids - A Tabular Review

45

Table 1. Continued 433 Secojollyanine Anisocycla jollyana Diels (Menispermaceae)[358]

C36H36O7N2:608.2522

393 Secolucidine Pseudoxandra sclerocarpa Maas (Annonaceae)[l 17]

C36H34O7N2:606.2366

269 Seco-obaberine Pseudoxandra aff. lucida Fries (Annonaceae)[8]

C38H40OgN2:652.2785

50

Sepeerine (Ocoteamine) C36H38O6N2:594.2730 Nectandra rodiei R. Schomb. (Lauraceae)[also known as Ocotea rodiei (Lauraceae)][236] Ocotea rodiei R. Schomb. (Lauraceae)[also known as Nectandra rodiei R. Schomb. (Lauraceae)][236]

371 Siddiquamine C35H30O6N2:574.2104 Coccuius pendulus (Forsk.) Diels (Menispermaceae)[233] 372 Siddiquine C34H28O6N2:560.1947 Coccuius pendulus (Forsk.) Diels (Menispermaceae)[233] 270 Sindamine Berberis lycium (Royle) (Berberidaceae)[68] 51

C37H3808N2:638.2628

Stebisimine C36H34O6N2:590.2417 Anisocycla gradidieri H. Bn. (Menispermaceae)[165] Coccuius japonica DC. (Menispermaceae)[also called Coccuius japonic us Thunb.) Miers (Menispermaceae)][264,431 ] Stephania japonica (Thunb.) Miers (Menispermaceae)[also called Coccuius japonicus D C (Menispermaceae)][264,431] Stephania japonica (Thunb.) Miers var australis (Menispermaceae)[264] Triclisia gilletii (DeWild.) Staner (Menispermaceae)f 168,281]

373 Stephasubimine Stephania suberosa Forman (Menispermaceae)[137]

C35H30O6N2:574.2104

374 Stephasubine C36H34O6N2:590.2417 Stephania hernandifolia (Willd.) Walp. (Menispermaceae) [also called Stephania discolor Spreng. (Menispermaceae)][249] Stephania suberosa Forman (Menispermaceae)! 137] 375 Stephibaberine Stephania erecta Craib. (Menispermaceae)[135] Stephania pierrii Diels (Menispermaceae)[34]

C37H40O6N2:608.2886

46


376 Stepierrine Stephania pierrii Diels (Menispermaceae)[34]

C33H3206N2:5 76.2260

426 Sutchueneneonine Cyclea sutchuenensis Gagnep. (Menispermaceae)[309]

CJ6H40O6N2:596.2886

427 Sutchuenenine Cyclea sutchuenensis Gagnep. (Menispermaceae)[309)

C36H40O6N2:596.2886

271 Talcamine Berberis buxifolia Lam. (Berberidaceae)[123]

C40H44Ol0N2:712.2996

160 Telobine C35H3405N2:562.2468 Daphnandra apatela Schodde (Monimiaceae)[ 11 ] Daphnandra species Dt-7 (Monimiaceae)[255] Guatteria guianensis (Aublet) R.E. Fries (Annonaceae)[ 119] 251 Temuconine Berberis valdiviana (Berberidaceae)[432]

C37H4206N2:610.3043

91

(+)-Tenuipine Daphnandra species unnamed (Monimiaceae)[234] Daphnandra tenuipes Perk. (Monimiaceae)[387]

C3gH40O7N2:636.2836

92

(-)-Tenuipine Daphnandra dielsii Perk. (Monimiaceae)[27] Daphnandra tenuipes Perk. (Monimiaceae)[27]

C3lH40O7N2:636.2836

76

(+)-Tetrandrine C38H42O6N2:622.3043 Aristolochia debilis Sieb. & Zucch. (Aristolochiaceae)[433] Cocculus pendulus (Forsk.) Diels (Menispermaceae)[ 139,161] Cocculus sarmentosus Diels (Menispermaceae)[332] Cyclea barbata (Wall.) Miers (Menispermaceae)[210,303,314 - 76 or 77] Cyclea burmanni (DC.) Miers ex. Hook. f. & Thorns. (Menispermaceae)[ 164,434] Cyclea peltata Diels (Menispermaceae)[43,267] Isopyrum thalictroides L. (Ranunculaceae)[323] Pachygone dasycarpa Kurz (Menispermaceae)[7] Stephania hernandifolia (Willd.) Walp. (Menispermaceae)[also called Stephania discolor Spreng. (Menispermaceae)][199] Stephania tetrandra S. Moore (Menispermaceae)[ 107,207,269,270,435,436]; ([268] detected, not isolated) Strychnopsis thouarsii Baill. (Menispermaceae)[272] Triclisia subcordata Oliv. (Menispermaceae)[42]

The Blsbenzylisoquinoline Alkaloids - A Tabular Review

47

Table 1. Continued

77

(+/-)-Tetrandrine C3gH42O6N2:622.3043 Cyclea barbata (Wall.) Miers (Menispermaceae)[89][303 - 76 or 77] Cyclea peltata Diels (Menispermaceae)[267] Isopyrum thalictroides L. (Ranuncuiaceae)[323] Stephania hernandifolia (Willd.) Walp. (Menispermaceae)[also called Stephania discolor Spreng. (Menispermaceae)][199]

78 Tetrandrine Mono-N-2'-Oxide C38H4207N2:638.2992 Cyclea barbata (Wall.) Miers (Menispermaceae)(78)[143] 106a Thalabadensine C36H38O6N2:594.2730 Thalictrum minus L. (Ranunculaceae)[369] Thalictrum sultanabadense Stapf. (Ranunculaceae)[297-300] 102 Thalfine (Thalphine) Thalictrum foetidum L. (Ranunculaceae)[437,438] Thalictrum minus L. (Ranunculaceae)[404]

C38H3608N2:648.2472

103 Thalfinine (Thalphinine) Thalictrum foetidum L. (Ranunculaceae)[437,438] Thalictrum minus L. (Ranunculaceae)[404]

C39H42OgN2:666.2941

99

Thalfoetidine (Thalictrinine) C38H4207N2:638.2992 Thalictrum fargesii Fr. ex Fin. et Gagnep. (Ranunculaceae)[439,440] Thalictrum flavum L. (Ranunculaceae)[ 108,289] Thalictrum longipedunculatum E. Nik. (Ranunculaceae)[363]

14

Thalibrine C38H4406N2:624.3199 Thalictrum longistylum DC. (Ranunculaceae)[246] Thalictrum rochebrunianum Franc, and Sav. (Ranunculaceae)[389]

112 Thalibrunimine C38H40O8N2:652.2785 Thalictrum rochebrunianum Franc, and Sav. (Ranunculaceae)[441,442] 113 Thalibrunine C39H44O8N2:668.3098 Thalictrum rochebrunianum Franc, and Sav. (Ranunculaceae)[441,442] 97

Thalicberine C37H40O6N2:608.2886 Thalictrum longipedunculatum E. Nik. (Ranunculaceae)[363] Thalictrum lucidum L. (Ranunculaceae)[37] Thalictrum minus L. (Ranunculaceae)[364,368,370,371] Thalictrum minus L. var. majus (Ranunculaceae)[373] Thalictrum minus L. var. microphyllum Boiss. (Ranunculaceae)[38]

P.L.SchifT,Jr. Table 1. Continued Thalictrum minus L. var. minus (Ranunculaceae)[375] Thalictrum thunbergii DC. (Ranunculaceae)[378] 107 Thalictine C37H40O6N2:608.2886 Thalictrum cultratum Wall. (Ranunculaceae)[307] Thalictrum sultanabadense Stapf. (Ranunculaceae)[300,380] Thalictrum thunbergii DC. (Ranunculaceae)[443] 220 Thalictrinine C38H3609N2:664.2421 Thalictrum rochebrunianum Franc, and Sav. (Ranunculaceae)[250] 100 Thalidasine C39H4407N2:652.3149 Thalictrum alpinum L. (Ranunculaceae)[247] Thalictrum cultratum Wall. (Ranunculaceae)[241 ] Vialictrum dasycarpum Fisch. and Lall. (Ranunculaceae)[444] Thalictrum faberi Ulbr. (Ranunculaceae)[242,243,445] Thalictrum fargesii Fr. ex Fin. et Gagnep. (Ranunculaceae)[439,440] Thalictrum flavum L. (Ranunculaceae)[289] Thalictrum foetidum L. (Ranunculaceae)[446] Thalictrum foliolosum DC. (Ranunculaceae)[447] Thalictrum longipedunculatum E. Nik. (Ranunculaceae)[363] Thalictrum lucidum L. (Ranunculaceae)[37] Thalictrum minus L. (Ranunculaceae)[404] Thalictrum revolutum DC. (Ranunculaceae)[376] Thalictrum rugosum Ait. (Ranunculaceae)[also called Thalictrum glaucum Desf. (Ranunculaceae)] [406] Thalictrum squarrosum Steph. ex Willd. (Ranunculaceae)[448] 377 Thalidasine-2a-N-Oxide Thalictrum cultratum Wall. (Ranunculaceae)[35]

C3«,H44OgN2:668.3098

83 Thalidezine C38H4207N2:638.2992 Thalictrum delavayi Franch. (Ranunculaceae)[286] Thalictrum fendleri Engelm. ex Gray (Ranunculaceae)[288] Thalictrum flavum L. (Ranunculaceae)[289] Thalictrum foetidum L. (Ranunculaceae)[290] Thalictrum glandulosissimum (Finet et Gagnep.) W.T. Wang et S.H. Wang (Ranunculaceae)[291,292] Thalictrum minus L. (Ranunculaceae)[365] Thalictrum podocarpum Humb. (Ranunculaceae)[244] Thalictrum rugosum Ait. (Ranunculaceae)[also called Thalictrum glaucum Desf. (Ranunculaceae)] [365] Thalictrum simplex L. (Ranunculaceae)[296]

The Bisbenzylisoqtiinoline Alkaloids - A Tabular Review

49

Table 1. Continued

428 Thalifortine Thalictrum fortune i S. Moore (Ranunculaceae)[36] 100a Thaligosidine C37H40O7N2:624.2836 Thalictrum rugosum Ait. (Ranunculaceae)[also called Thalictrum glaucum Desf. (Ranunculaceae)][449] 52a Thaligosine [see Thalisopine (54)] C38H4207N2:638.2992 The following alkaloids were named thaligosine, but the existence of an identical alkaloid, thalisopine, in the literature mandates the use of the latter designation [471] Thalictrum cultratum Wall. (Ranunculaceae)[35] Thalictrum foetidum L. (Ranunculaceae)[290] Thalictrum minus L. var. majus (Ranunculaceae)[373] Thalictrum rugosum Ait. (Ranunculaceae)[also called Thalictrum glaucum Desf. (Ranunculaceae)] [449] 378 Thaligosine-2o>N-Oxide (Thalisopine-2a-N-Oxide) Thalictrum cultratum Wall. (Ranunculaceae)[35]

C38H4208N2:654.2941

52b Thaligosinine C38H4207N2:638.2992 Thalictrum fargesii Fr. ex Fin. et Gagnep. (Ranunculaceae)[439] Thalictrum foetidum L. (Ranunculaceae)[446] Thalictrum isopyroides C.A.M. (Ranunculaceae)[450] Thalictrum rugosum Ait. (Ranunculaceae)[also called Thalictrum glaucum Desf. (Ranunculaceae)] [449] 252 Thaligrisine Pseudoxandra sclerocarpa Maas (Annonaceae)[ 117] Thalictrum minus L. var. microphyllum Boiss.[38]

C37H4206N2:610.3043

253 Thaliphylline Thalictrum cultratum Wall. (Ranunculaceae)[307] Thalictrum minus L. var. microphyllum Boiss.[38] Thalictrum minus L. var. minus (Ranunculaceae)[375]

C37H40O6N2:608.2886

379 Thaliphylline-2'p-N-Oxide Thalictrum cultratum Wall. (Ranunculaceae)[35]

C37H40O7N2:624.2836

17a Thalirabine Thalictrum baicalense Turcz. (Ranunculaceae)[245] Thalictrum minus L. (Ranunculaceae)[404]

C40H47OgN/:683.3332

50


14a Thaliracebine Thalictrum faberi Ulbr. (Ranunculaceae)[243] Thalictrum minus L. (Ranunculaceae)[404]

C39H4407N2:652.3149

17b Thalirugidine Thalictrum foliolosum DC. (Ranunculaceae)[451 ] Thalictrum rugosum Ait. (Ranunculaceae)[449]

C39H46O8N2:670.3254

14b Thalirugine C3lH44O7N2:640.3149 Thalictrum cultratum Wall. (Ranunculaceae)[35] Thalictrum minus L. var. microphyllum Boiss. (Ranunculaceae)[38] Thalictrum rugosum Ait. (Ranunculaceae)[also called Thalictrum glaucum Desf.(Ranunculaceae)] [449] 14c Thaiiruginine C3gH46O7N2:654.3305 Thalictrum rugosum Ait. (Ranunculaceae)[also called Thalictrum glaucum Desf.(Ranunculaceae)][449] 84

Thalisamine Thalictrum simplex L. (Ranunculaceae)[296]

C38H4207N2:638.2992

53

Thalisopidine C37H40O7N2:624.2836 Thalictrum isopyroides C.A.M. (Ranunculaceae)[450,452,453]

54

Thalisopine C38H4207N2:638.2992 Thalictrum cultratum Wall. (Ranunculaceae)[35,307] Thalictrum faberi Ulbr. (Ranunculaceae)[359] Thalictrum foetidum L. (Ranunculaceae)[290] Thalictrum foliolosum DC. (Ranunculaceae)[451 ] Thalictrum isopyroides C.A.M. (Ranunculaceae)[452] Thalictrum javanicum Bl. (Ranunculaceae)[454] Thalictrum minus L. var. majus (Ranunculaceae)[373] Thalictrum minus L. var. microphyllum Boiss. (Ranunculaceae)[38,374] Thalictrum revolutum DC. (Ranunculaceae)[376] Thalictrum rugosum Ait. (Ranunculaceae)[also called Thalictrum glaucum Desf. (Ranunculaceae)] [449]

221 Thalistine Thalictrum minus L. race B (Ranunculaceae)[360]

C3QH44O,N2:668.3098

18 Thalistyline Thalictrum longistylum DC. (Ranunculaceae)[246] Thalictrum podocarpum Humb. (Ranunculaceae)[244]

C4IH49OgN2+:697.3489


51

Table 1. Continued

380 Thalivarmine Thalictrum minus L. var. minus (Ranunculaceae)[375] 98

C36H3gO6N2:594.2730

Thalmethine C36H3606N2:592.2573 Thalictrum minus L. (Ranunculaceae))[364,368,369,371,379,455]

381 Thalmiculatimine Thalictrum cultratum Wall. (Ranunculaceae)[307]

C36H3606N,:592.2573

382 Thalmiculimine Thalictrum cultratum Wall. (Ranunculaceae)[307]

C37H3807N2:622.2679

383 Thalmiculine Thalictrum cultratum Wall. (Ranunculaceae)[307]

C38H4207N2:638.2992

108 Thalmine Thalictrum cultratum Wall. (Ranunculaceae)[241] Thalictrum kuhistanicum Ovcz. (Ranunculaceae)[362] Thalictrum minus L. (Ranunculaceae)[366,369,455]

C37H40O6N2:608.2886

222 Thalmirabine Thalictrum delavayi Franch. (Ranunculaceae)[286] Thalictrum minus L. race B (Ranunculaceae)[360]

C3QH44O8N2:668.3098

223 Thalpindione

C 3 7 H 3 6 O Q N 2 :652.2421

Thalictrum alpinum L. (Ranunculaceae)[247] 52

C37H40OAN2:608.2886 Thalrugosamine [see Homoaromoline (42)][3] The following alkaloids were formerly named thalrugosamine, but a reevlaution of the assignment of the structure of thalrugosamine published in 1972 [305] demonstrated an inconsistency in the structural representation (but not the actual work of the alkaloid [DF3,DG3] with the revelation that (+)-thalrugosmine was in reality (+)- homoaromoline [38]: Limaciopsis loangensis Engl. (Menispermaceae)[92] Stephania pierrii Diels (Menispermaceae)[34] Stephania venosa Spreng. (Menispermaceae)[306] Thalictrum rugosum Ait. (Ranunculaceae)[also called Thalictrum glaucum Desf. (Ranunculaceae)] [3 05 ]

55 Thalrugosaminine (O-Methylthalisopine) Thalictrum alpinum L. (Ranunculaceae)[247] Thalictrum cultratum Wall. (Ranunculaceae)[35,307] Thalictrum foetidum L. (Ranunculaceae)[446]

C39H4407N2:652.3149

P.L.Schiff,Jr. Table 1. Continued Thalictrum foliolosum DC. (Ranunculaceae)[451] Thalictrum javanicum Bl. (Ranunculaceae)[454] Thalictrum minus L. (Ranunculaceae)[404] Thalictrum rugosum Ait. (Ranunculaceae)falso called Thalictrum glaucum Desf. (Ranunculaceae)][456] 384 Thalrugosaminine-2a-N-Oxide Thalictrum cultratum Wall. (Ranunculaceae)[35]

C37N2 Daphnine(191)[213-215] C3gH3606N2 616.2573 Phaeantharine (73)[162,163] C37H3407N2 618.2366 Oxofangchirine (349)[410] 620.2523 C37H3607N2 Curicycleatjine (401)[174] Guattaminone (304)[119] Isocuricycleatjine (411)[174] Oxoepistephanine (47a)[409] Repanduline (168)[27,426] C38H40O6N2 620.2886 Dimethylwarifteine (148)[251] Insularine (170)[182,189,192,252,308,310] 622.2316 C36H34OgN2 Gilgitine (261)[68] C37H3gO?N2 622.2679 Cepharanthine-2'p-N-Oxide (282)[ 137] (+)-Nortenuipine(88)[255,387,336] (-)-Nortenuipine (89)[27,387] Oxandrine (347)[408] Oxandrinine (348)[408]

141

P.L.Schiff,Jr. Table 5. Continued Pseudoxandrine (368)[408] Thalmiculimine (382)[307] Thalsimidine (85)[462] C38H4206N2 622.3043 Cycleaneonine (286)[187,188] (-)-Cycleaneonine (403)[188] Cycleanine (121)[30,32,34,92,102,104,105,131,132,141,142,147,157,158,181,182,189, 190-195,197,204-208] Dimethyldihydrowarifteine (147)[251 ] Funiferine (20)[ 119,275,276] Gyrolidine (308)[282] Isocycleaneonine (412)[188] Isotetrandrine (62)[ 18,19,21,23,28-30,32,34,51,55,58,64,69,72,79,80,87,91,92,95, 97-100,101,103,104,108,112,135,153,168,269,282,302,319-328] 0-Methylisothalicberine(94)[48,237,337] O-Methyllimacusine (320)[282] 0-Methylrepandine(45)[27,323,336] O-Methylthalicberine (95)[37,38,116,238,289,290,307,359,362-378] O-Methylthalmine (244)[307,380] Monterine(324)[172] Obaberine (46)[8,16,18,19,34,35,37,39,49,60,62,135,230,232,248,320,322,337,373,374, 400-404] Phaeanthine (74)[22,45,99,100,101,164,168,282,342,422-424] Rodiasine (26)[236,388] (+)-Tetrandrine (76)[7,42,43,107,139,161,164,199,207,210,267-270,272,303,314,323, 332,433-436] (+/-)-Tetrandrine (77)[89,199,267,303,323] C3lH«306N2+ 623.3121 2-N'-Methylberbamine (66a)[l 16,351,352] 2-N-Methylfangchinoline(416)[355] Oblongamine (47)[115] C^H^N, 624.2836 Berbamine-2'P-N-Oxide (274)[58] Chenabine (258)[138] N-Desmethylthalidezine (80)[244] N-Desmethylthalrugosidine (197)[247] Fenfangjine B (Fangchinoline-2'a-N-Oxide) (298)[207,273] Fenfangjine C (Fangchinoline-2'P-N-Oxide) (299)[207,273] Fenfangjine D (1,3,4-Tridehydrofangchinolinium Hydroxide) (300)[207,274] 5-Hydroxythalmine (313)[307]

The Bisbenzylisoquinoline Alkaloids - A Tabular Review Table 5. Continued Limacine-2'a-N-Oxide (315)[ 127-129] Limacine-2p-N-Oxide (316)[ 127-129] Limacine-2'P-N-Oxide (317)[ 127-129] Limacusine-2'P-N-Oxide(413)[235] 2-Norobaberine-2'p-N-Oxide (424)[ 151] Thaligosidine (100a)[449] Thaliphylline-2'P-N-Oxide(379)[35] Thalisopidine (53)[453] C3gH44OftN2 624.3199 Chondocurarine (129)[140] Dauricine (3)[218-229] Isochondocurarine (174)(bisquaternary)[311] 7'-0-Methylcusidaline (240)[353] 7-O-Methylgrisabine (417)[252] Neferine (30)[317,339] (+)-Neochondocurarine (175)(bisquaternary)[311] Neothalibrine(211)[35,39,247,377] Pisopowetine (358)[229] Pisopowiarine (360)[229] Popidine (363)[229] Popisidine (364)[229] Popisine (365)[229] Thalibrine (14)[246,389] C37H4207N2 626.2992 Chillanamine (229)[123] Magnolamine (15)[344] 632.2734 C J6 H 4 AN 2 Pycnarrhenamine (181)[100] 634.2679 C37H3807N2 Curicycleatjenine (400)[174] Isocuricycleatjenine (410)[ 174] C37H3608N2 636.2472 Secocepharanthine (268)[248] 636.2836 C38H40O7N2 Calafatimine(190)[121] Cycleanine N-Oxide (232)[158] lnsularine-2p-N-Oxide (408)[252]

143

P.L.Schifr,Jr. Table 5. Continued Insularine-2'p-N-Oxide (409)[252] Isotenuipine (87)[318] O-Methylthalibrine(209)[292,359,360] Oxandrinine (348)[408] Pseudoxandrinine (369)[408] Repandinine (90)[27,336,387] (+)-Tenuipine (91)[234,387] (-)-Tenuipine (92)[27] Thalsimine (86)[296,365,441,462,463] C39H4406N, 636.3199 Granjine (302)[172] 637.3278 C39H4506N2* Cycleahomine (59)[43] N-2'-Methylisotetrandrine (319)[70] Monomethyltetrandrinium (67)[383] 638.2628 C37H3„OgN2 Baluchistanamine (257)[46] Dihydrosecocepharanthine (260)[248] Maroumine (391)[45] Secantioquine (267)[8,430] Secohomoaromoline (432)[358] Sindamine (270)[68] 638.2992 C38H4,07N, N-Desmethylthalidasine (196)[241 -243] Epinorhernandezine (199)[250] Fenfangjine A (Tetrandrine-2p-N-Oxide) (297)[207,273] Funiferine N-Oxide (21)[278] Isothalidezine (82)[244,286,292] N'-Norhernandezine (212)[250] Osornine (248)[123] N-Oxy-2'-Isotetrandrine (216)[92] Phaeanthine-2'a-N-Oxide (356)[101] Tetrandrine Mono-N2'-Oxide (78)[143] Thalfoetidine (99)[ 108,289,363,439,440] Thalidezine(83)[244,286,288-292,296,365] Thalisopine(Thaligosine)(54)[35,38,290,307,359,373,374,376,449,451,452,454,471] Thaligosinine(52b)[439,446,449,450] Thalisamine (84)[296] Thalmiculine (383)[307]

The Bisbenzylisoquinoline Alkaloids - A Tabular Review Table 5. Continued

Thalrugosidine(101)[247,307,359,406,447,451] C39H4606N, 638.3356 O,O'-Dimethylgrisabine(~407)[252,253] O-Methyldauricine (12a)[229,354] Pisopowidine (361)[229] C38H4407N, 640.3149 Neothalibrine-2'a-N-Oxide(325)[35] Thalirugine (14b)[35,38,449] C38H40O8N2 646.2890 Pycnarrhenine (182)[100] 648.2472 C38H3608N, Thalfine (102)[404,437,438] C37H36OqN2 652.2421 Thalpindione (223)[247] 652.2785 C38H40O8N2 Auroamine (390)[45] Revolutinone (266)[427] Secoisotetrandrine (431)[325J Seco-obaberine (269)[8] Thalibrunimine (112)[441,442] C39H4407NU 652.3149 Calafatine(190)[121-124] Hernandezine (81)[161,244,284-300] Thalidasine(100)[37,241.243,247,289,363,376,404,406,439,440,445-448] Thaliracebine (14a)[243,404] Thalrugosaminine (55)[35,247,307,404,446,451,454,456] 652.3512 C40H48O6N2 Funiferine Dimethiodide (201)(bisquaternary)[277] Pisopowine (362)[229] C38H4208N2 654.2941 Epinortbalibrunine (200)[250] N'-Northalibrunine (214)[250,361] Thaligosine-2a-N-Oxide (Thalisopine-2a-N-Oxide) (378)[35]

14S

P.L.SchifT,Jr. Table 5. Continued 654.3305

CJOH^N,

N-2-Oxy-O-Methyldauricine(350)[229] N-2'-Oxy-0-Methyldauricine(351)[229] Thaliruginine (14c)[449] 656.3097 C38H4408N2 Ambrimine (272)[6] Efatine (296)[6] Vateamine (256)[345] 664.2421 C38H3609N2 Thalictrinine (220)[250] C39H40OgN2 664.2785 Tiliacoridine (183)[464] 666.2577 C3gH380QN2 Dihydrothalictrinine (198)[250] Oxothalibrunimine (215)[250] Thalrugosinone (224)[39,241] C39H4208N2 666.2941 O-Methylthalibrunimine (210)[361 ] Thalfinine (103)[404,437,438] 668.2734 C38H40O9N, Pycmanilline(392)[101] 668.3098 C39H4408N, Calafatine-2'a-N-Oxide (~226)[ 125,126] Calafatine-2'p-N-Oxide (227)[ 125,126] Hernandezine-N-Oxide (203)[299] 5-Hydroxythalidasine (311)[307] Thalibrunine (113)[441,442] Thalidasine-2a-N-Oxide (377)[35] Thalistine (221)[360] Thalmirabine (222)[286,360] Thalrugosaminine-2a-N-Oxide (384)[35] 670.3254 C39H46OgN2 Malekulatine (238)[345-347] Thalirugidine (17b)(449,451] Vanuatine (255)[345]

l he Bisbenzylisoquinoline Alkaloids - A Tabular Review

147

Table 5. Continued C38H44OqN, 672.3047 Vateamine-2'-P-N-Oxide(430)[472] 682.2891 C39H4209N2 Curacautine (259)[123] 682.3254 C40H46OgN2 N-Desmethylthalistyline (16)[244-246] 683.3332 C40H47O8N/ Thalirabine (17a)[245.404] 684.3046 C39H4409N2 5-Hydroxythalidasine-2a-N-Oxide (312)[35] C4lH49OgN/ 697.3489 Thalistyline (18)[244,246~] 712.2996 C40H44O,0NU Talcamine (271)[123] C42HoOgN2*4 712.3724 N-Methylthalistyline (17)[244,246] 7.

A TABULAR COMPILATION OF THE STRUCTURAL TYPES OF THE BISBENZYLISOQUINOLINE ALKALOIDS Table 6

I.

One Diphenyl Ether Linkage (Tail-to-Tail) Type I - 6,7,11\12-6,7,12* (XJt) Costaricine(399)[173] Cuspidaline(2)[l84,185] Dauriciline(406)[217] Dauricine (3)[218-228J Dauricinoline (4)[222,223] Dauricoline (5)[221,223,229] Daurinoline (6)[220,221,223] Daurisoline(192)[223,225,227,230,231]

H8

P.L.Schiff,Jr. Table 6. Continued N'-Desmethyldauricine (7)[220] N,N'-Dimethyllindoldhamine (Guattegaumerine)(234)[74,76,230,231,254] Geraldoamine (301)[279] Isodaurisoline (235)[231] Lindoldhamine (11)[ 10,16,230,231,343] 7'-O-Methylcuspidaline(240)[353] O-Methyldauricine (12a)[229,354] 2-N-Methyllindoldhamine (321 )[230] 2'-N-MethyIlindoldhamine(322)[230] 7-O-Methyllindoldhamine (241)[231 ] 7'-0-MethylIindoldhamine (242)[231 ] 2'-Nordaurisoline (330)[230] N-2-Oxy-O-Methyldauricine(350)[229] N-2'-Oxy-0-Methyldauricine(351)[229] Pampulhamine (352)[279] Pedroamine (355)[279] Popidine (363)[229] Popisidine (364)[229] Popisine (365)[229] Popisonine (366)[229] Popisopine (367)[229] (R,S) Berbamunine (1)[ 18,19,21,23,34,62,76,82,84.86,110-117] Espinidine (8)[265] Espinine (9)[239,265] Temuconine (251)[432] Thaligrisine(252)[38,117] (S,R) O,O'-Dimethylgrisabine(407)[252,253] Grisabine (10)[240,282,283] Magnoline (12)[240,344,475] 7-O-Methylgrisabine (417)[252] (S,S) O-Methylthalibrine(209)[292,359,360] Neothalibrine (211)[35,39,247,377]] Neothalibrine-2'a-N-Oxide(325)[35] Northalibrine (13)[389] Northalibroline (341)[390] Thalibrine (14)[246,389]

The Blsbenzylisoquinoline Alkaloids - A Tabular Review Table 6. Continued Type la - 6,7,11 ',12-5,6,7,12' Thaliracebine (14a)[243,404] Thalirugine (14b)[35,38,449] Thaliruginine (14c)[449] Type lb - 6,7,10,11\ 12-6,7,12* Chillanamine (229)[123] Type II - 6,7,10\12,13-6,7,12* Magnolamine (15)[344] Type Ha - 6,7,10M2,13-6,7,llM2 (S,S) Vanuatine (255)[345] Type lib - 6,7,10,11,12-6,7,11\12 (S,S) Vateamine (256)[345] Vateamine-2'.p-N-Oxide (430)[472] Type III - 5,6,7,1 1\12-5,6,7,12* (S,S) N-Desmethylthalistyline (16)[244-246] N-Methylthalistyline(17)[244,246] Thalirabine (17a)[245,404] Thalirugidine (17b)[449,451] Thalistine(221)[360] Thalistyline (18)[244,246] II.

One Diphenyl Ether Linkage (Head-to-Tail) Type V-6,7,11M2-6,7M2 <JW) Isoliensinine (28)[316,317] Liensinine(29)[338-341] Neferine (30)[317,339] Unknown stereochemistry Neosutchuenenine (420)[309]

149

150

P.L.Schitr,Jr. Table 6. Continued Type Va - 6,7,10\12,13-6,7\11,12 (S,S) Malekulatine (238)[345-347] Type Vb - 6,7,10\11,12-6,7\11,12 (S,S) Ambrimine (272)[6] Efatine (296)[6] Type Vc - 6,7\12-6,7,12* Unknown stereochemistry Sutchueneneonine (426)[309] Type Vd - 6,7\8,12-6,7,12* Unknown stereochemistry Sutchuenenine (427)[309]

III.

One Diphenyl Linkage (Tail-to-Tail) Type XXVII - 6,7,12-6,7,12(11-11) (R,R) 2'-Norpisopowiaridine (339)[229] Pisopowamine (357)[229] Pisopowetine (358)[229] Pisopowiaridine (359)[229] Pisopowiarine (360)[229] Pisopowidine (361)[229] Pisopowine (362)[229]

IV.

One Diphenyl Ether Linkage (Head-to-Head) and One Diphenyl Linkage (Tail-toTail) Type IV - 6,7,8\12-6,7\12(11-11) Cordobimine(283)[172] Guattamine (303)[119] Guattaminone (304)[119] Secantioquine (267)[8,430] (R,S) Cordobine (284)[172] Granjine (302)[172] Monterine(324)[172]


151

Table 6. Continued

(S,R) Antioquine (225)[8] Funiferine (20)[119,275,276] Funiferine Dimethiodide (201)[277] Funiferine N-Oxide (21)[278] 2'-Norfuniferine(331)[119] Norrodiasine (22)[119,236] 2'-Nortiliageine(345)[H9] Phlebicine (25)[ 119,425] Rodiasine (26)[ 119,236,388] Tiliageine (27)[119,275,466] Tilitriandrine (387)[466] (5,5) 2,2'-Bisnorguattaguianine (276)[119] 2'-Norguattaguianine (332)[119] Ocotine(23)[ 119,388] Oxandrine (347)[408] Oxandrinine (348)[408] Pseudoxandrine (368)[408] Pseudoxandrinine (369)[408] Unknown stereochemistry Dirosine (19)[236] V.

One Diphenyl Ether Linkage (Head-to-Head) and One Diphenyl Ether Linkage (Tailto-Tail) Type VI - 6,7\11\12-6,7,8\12 + (-,-) Stebisimine (51)[ 165,168,264,281,431 ] Stephasubimine (373)[137] (*,-) Colorflammine (219)[49,50] 3',4'-Dihydrostephasubine (295)[249] (+)-Epistephanine (40)[249,261 -264] Hypoepistephanine (43)[263] Norstephasubine (340)[137] Oxoepistephanine (47a)[409] Pangkorimine (354)[10] Pycnazanthine (370)[120] Stephasubine (374)[ 137,249]


(-)-Epistephanine (41)[165] (-,*) Auroamine (390)[45] 1,2-Dehydro-2-Norlimacusine (291 )[74] Maroumine (391)[45] (-,S) CocIobine(35)[12,151,152] Baluchistanamine (257)[46] 12-O-Demethylcoclobine (293)[12] Dihydrosecocepharanthine (260)[248] Secocepharanthine (268)[248] Secohomoaromoline (432)[358] Seco-obaberine (269)[8] (*,*) Candicusine (280)[127-129] Gyrocarpusine (307)[282] Limacusine (44)[ 127-129,184,185] Limacusine-2'p-N-Oxide (413)[235] O-Methyllimacusine (320)[282] 2-Norlimacusine (245)[74,283] Pangkoramine (353)[10] (R,S) Aromoline (31)[ 1,9,12,15-21,23,24,26-42,78] Baluchistine (188)[47] N,N'-Bisnoraromoline (32)[10,13,118] Cepharanoline (33)[32,102,104,130] Cepharanthine (34)[32,34102,104-106,131 -137] Cepharanthine-2'p-N-Oxide (282)[ 137] Daphnandrine (37)[ 10,12,13,27,28,34,90,135,151] Daphnoline (38)[7,9,10,12,13,16,26-28,49,120,139,216] Homoaromoline (42)[ 1,2,15,16,18,28,30,32,34,37,38,40,41,49,92,104,117,134, 210,235,301-306] 2-Norcepharanoline (326)[34] 2-Norcepharanthine (327)[135,137] 2'-Norcepharanthine (328)[34] 2-Norisocepharanthine (333)[34] 2'-Norobaberine (337)[34] 2-Norobaberine-2'p-N-Oxide (424)[ 151]


153

Table 6. Continued 2'-Noroxyacanthine (338)[35] Obaberine (46)[8,16,18,19,34,35,37.39,49,60.62,135,230,232,248,320.322,337,373, 374,400-404] Oxyacanthine(48)[ 16-18,20,21,24,35,37,55,60,62,63.65.68.70,75,78,79,83-86,95, 96,110-116,321,373,379,400,402,403,407,411.413-421,473] Sepeerine (50)[236] Stephibaberine (375)[34,135] Thalrugosamine (52) - see Homoaromoline (42) (S,R) Gyrocarpine (306)[45,282] Gyrolidine (308)[282] Macolidine (44a)[240] Macoline (44b)[240] (5,5) Cycleapeltine (36)[43.90,209] Demerarine (39)[236] Johnsonine (206)[336] 0-Methylrepandine(45)[27.323.336] Repandine (49)[90.336.426] Type Via - 6,7M0,llM2-6,7,8*,124 iS,R) Osornine (248)[123] Type VII - 5,6,7,8\12 + -6,7\U\12 (S,S) Thaligosine (52a) - see Thalisopine (54) Thaligosine-2a-N-Oxide - see Thalisopine-2a-N-Oxide Thaligosinine(52b)[439,446,449,450] Thalisopidine (53)[453] Thalisopine-2a-N-Oxide (378)[35] Thalisopine (54)[35,38,290,307,359,373,374.376,449.451.452,454,471] Thalrugosaminine (55)[35,247,307,404,446,451,454,456] Thalrugosaminine-2a-N-Oxide (384)[35] Type VIII - 6,7,8\11M2-6,7\12* Dehatrine (288)[232,474] Pycmanilline(392)[101] Secoisotetrandrine (432)[325]

154


Sindamine (270)[68] (-,*) Berbacolorflammine (218)[49,50] (-,5) Chenabine(258)[138] Cheratamine (228)[139] Dehatridine (287)[232] Fenfangjine D (1,3,4-Tridehydrofangchinolinium Hydroxide) (300) [207,274] Jhelumine (262)[138] Stepierrine (376)[34] Tiliafunimine (79a)[465]

(M Oxofangchirine (349)[410] (-,-) Phaeantharine (73)[162,163] (R,R) 2,2'-Bisnorphaeanthine (278)[10] Caryolivine (281)[74] Gyroamericine (305)[282] Krukovine (63)[ 15,49,127,128] Limacine (64)[22,45,49,89,127,128,184,185.209.210,235.271,272,282,301,342] Limacine-2'a-N-Oxide (315)[ 127-129] Limacine-2p-N-Oxide (316)[ 127-129] Limacine-2'P-N-Oxide (317)[ 127-129] 2-Norlimacine (336)[74,235] 2'-Norlimacine (423)[90,235] Phaeanthine (74)[22,45,99-101,164.168,282,342,422-424] Phaeanthine-2'a-N-Oxide (356)[ 101] Pycnamine (75)[22,100,101,168,422] (R,S) Aquifoline (273)[14] Berbamine (57)[ 17-20,22,23,29,30,32,51 -109] Berbamine-2'p-N-Oxide (274)[58] Bisnorobamegine (277)[120] Bisnorthalrugosine (279)[120]


155

Table 6. Continued Cycleabarbatine (402)[90] Isotetrandrine (62)[ 18,19.21,23,28,29,30,32,34,51,55,58,64,69,72,79,80,87,91,92,95, 97-104,108, M 2,135,153,168,269,282,302,319-328] 2-N'-Methylberbamine (66a)[l 16,351,352] N-2'-Methyiisotetrandrine (319)[70] 2-N-Norberbamine (68)[34,99,120,139] 2-Norisotetrandrine (334)[34,135] Nor-2'-Isotetrandrine(213)[34,92] 2-Norobamegine (69)[99,118,120] 2-Northalrugosine (344)[120,135] Obamegine (71)[ 18,19,29,32,37,38,281,400,403,405,406,407] N-Oxy-2'-Isotetrandrine (216)[92] Thalrugosine (79)[ 18,19,22,37,92,135,210,266,360,374,402,403,406,457-461 ] (S,R) 7-O-Demethylpeinamine (60a)[240] Peinamine (71a)[240] (5,5) Atherospermoline (56)[7,44] Cycleahomine (59)[43] Cycleanorine (60)[43,90] Fangchinoline (61 )[7,43,107,168,199,207,255,266-272] Fenfangjine A (Tetrandrine-2P-N-Oxide) (297)[207,273] Fenfangjine B (Fangchinoline-2'a-N-Oxide) (298)[207.273] Fenfangjine C (Fangchinoline-2'P-N-Oxide) (299)[207,273] 2-N-Methylfangchinoline(416)[355] Monomethyltetrandrinium (67)[383] Norpenduline(246)[139] 2-Nortetrandrine (70)[388] Penduline (72)[7,58,139,153,155,156,160,161 ] (+)-Tetrandrine (76)[7,42,43,107,139,161,164,199,207,210.267-270,272,303,314, 323,332,433-436] Tetrandrine Mono-N2'-Oxide (78)[143] Racemate

Cycleadrine (Fangchinoline (61) racemate)(58)[l,43] (+/-)-Tetrandrine (77)[89,199,267,303,323] Isomorph Menisidine (65)(Isomorph of Fangchinoline (61))[350] Menisine (66)(Isomorph of (+)-Tetrandrine (76))[350]

P.L. Schiff, Table 6. Continued Type IX - 5,6,7,8\11M2-6,7M2+ Thalsimidine (85)[462] Thalsimine (86)[296,365,441,462,463] (S,R) Epinorhernandezine (semisynthetic)( 199)[250] Isothalidezine (82)[244,286,292] (S,S) N-Desmethylthalidezine (80)[244] Hernandezine (81)[ 161,244,284-300] Hernandezine-N-Oxide (203)[299] N'-Norhernandezine (212)[250] Thalidezine(83)[244,286,288-292,296,365] Thalisamine (84)[296] Type X - 6,7,8\11\12,13-6,7\12 + (R,R) (-)-Nortenuipine (89)[27,387] (-)-Tenuipine (92)[27] (R,S) Isotenuipine (87)[318] (S,S) (+)-Nortenuipine(88)[255,336,387] (+)-Tenuipine (91)[234,387] Racemate Repandinine (90)[Tenuipine (91) racemate] [27,3 36,3 87] Type Xa - 6,7,8\10,HM2-6,7\12* Calafatimine(189)[121] Curacautine (259)[123] Talcamine (271)[ 123] (S,R) Calafatine (190)[12M24] Calafatine-2'a-N-Oxide (226)[ 125,126] Calafatine-2'P-N-Oxide (227)[ 125,126]

The Bisbenzyllsoquinollne Alkaloids - A Tabular Review Table 6. Continued Type Xb - 6,7\8,11M2,13-6,7\12* (-,-) Daphnine(191)[213-215] Type XI - 6,7,8\11M2,-6\7,12 + (5,-) 0-Methylthalmethine(96)[364,368,371,375.376.379] Thalmethine(98)[364,368,369,371,379,455] Revolutinone (266)[427] Thalsivasine (385)[307.375] (R,S) Belarine (93)[ 18,48] 7-O-Demethylisothalicberine (195)[ 18,237,238] Isothalicberine (205)[237,238] 0-Methylisothalicberine(94)[48,237,337]

W5) O-Methylthalicberine (95)[37,38.116,238,289.290.307,359,363-378] 2'-Northaliphylline (342)[35,307] Thalicberine(97)[37,38,363,364,368,370,371,373.375,378] Thaliphylline (253)[38,307,375] Thaliphylline-2'p-N-Oxide(379)[35] Thalivarmine (380)[375] Type XII - 6,7,8\11+,12-5\6,7,124 (5,5) Thalfoetidine (99)[ 108,289,363,439,440] N-Desmethylthalidasine(196)[241-243] N-Desmethylthalrugosidine (197)[247] Thalidasine(100)[37,241-243,247,289,363,376,404,406,439,440,444-448] Thalidasine-2a-N-Oxide (377)[35] Thaligosidine (100a)[449] Thalpindione (223)[247] Thalrugosidine(101)[247,307,359,406,447,451] Thalrugosinone (224)[39,241 ] Type XHa - 5,6,7,8\H\12-5\6,7,12 + (5,5) 5-Hydroxythalidasine (311)[307] 5-Hydroxythalidasine-2a-N-Oxide (312)[35]

157

P.L. Schiff,Jr. Table 6. Continued Type XIII - 5\6,7,11M2,-5,6,7,8\12+ Thalfine (102)[404,437,438] (S,S) Thalfinine (103)[404,437,438] Thalmirabine (222)[286.360] Type XIV - 6,7\11+,12,-5\6,7,12+ (S,-) Thalmiculatimine (381)[307] (R,S) Berbilaurine(275)[18] 12-O-Desmethyllauberine (294)[239] Lauberine(106)[18,337] (S,R) Dryadine (104)[260] Dryadodaphnine (105)[260] Thalifortine (428)[36] (S,S) O-Methylthalmine (244)[307,380] 2-Northalmine(343)[241] Thalabadensine (106a)[297-300,369] Thalictine(107)[300,307,380,443] Thalmine (108)[241,363,366,369,455] Type XlVa - 5,6,7\11M2-5*,6,7,12* Cultithalminine (285)[35] Thalmiculimine (382)[307] (S,S) 5-Hydroxythalmine (313)[307] Thalmiculine (383)[307] Type XV - 5\6,7,U\12,-6,7\12 + (R,R) Norpanurensine (109)[386] Panurensine(110)[386]


159

Table 6. Continued Type XVI - 5\6,7,11+,12,-6*,7,12+ (R,R) Nemuarine(lll)[384] Type XVII - 5,6,7,8*, 10M 1,12,-6,7\12+ Dihydrothalictrinine (198)[250] O-Methylthalibrunimine (210)[361] Oxothalibrunimine (215)[250] Thalibrunimine (112)[441,442] Thalictrinine (220)[250] (S,R) Epinorthalibrunine (semisynthetic)(200)[250] (S,S) N'-Northalibrunine (214)[250,361] Thalibrunine (113)[441,442] VI.

One Diphenyl Ether Linkage (Head-to-Tail) and One Diphenyl Ether Linkage (Headto-Tail) Type XX - 6,7,8\12+-6,7,8*12* Sciadoline (128)[ 198,429] Sciadoferine (217)[ 198] (R,R) Cycleanin«121)[30,32,34,92,102,104,105,131,132.141,142.147,157,158,181,182, 189-195,197,204-208] Cycleanine N-Oxide (232)[158] N-E>esmethylcycleanine (233)[34,206] Isochondodendrine(122)[ 144,146,312,141,142,201,313,189,190,175, 314,315,267,194,195,196,197,180,182,183,199.198,303,175,181, 147,130,309] (-)-Norcycleanine (125)[181,32] (S,R) Sciadenine (127)[428,198] (SfS) (+)-Norcycleanine (124)f312,141,192,195,158]

P.L.Schlff,Jr. Table 6. Continued Unknown stereochemistry Neoprotocuridine (123)[ 1 ] Protocuridine (126)[1] Type XXI - 6,7,8*,ll\12-6,r, 12* (R,R) (-)-Curine (133)[90,130,141,142,144,145,147,1 75-183,190.200-203] Cycleacurine (134)[43] 0,0-DimethyIcurine (135)[ 191,196] Isocuricycleatjenine (410)[I74] Isocuricycleatjine (411)[174] 12'-0-MethyIcurine (140)[196] (R,S) Chondocurarine (129)[140] Chondocurine (130)[141-145] (+)-Tubocurarine (142)[142,145,470] (-)-Tubocurine (144)[201] Nor-Nb-Chondrocurine (230)[145] (S,R) Curicycleatjenine (400)[174] Curicycleatjine (401)[ 174] Hayatidine(136)[190] (-)-Tubocurarine (143)[200] (S,S) Chondrofoline (131)[147,148,175] (+)-Curine (132)[146,175-178] 4"-0-Methylcurine (139)[ 175,203] Racemate

(+/-)-Curine dimethiodide (132)[476] Unknown stereochemistry Hayatine (137)[ 144,175,190,202] Hayatinine (138)[ 190,202] Mixture Toxicoferine (141)[201 ] -1:1 mixture of (-)-Curine (133) and (-)-Tubocurinc (144)


161

Table 6. Continued VII.

Two Diphenyl Ether Linkages (Head-to-Head) and One Diphenyl Linkage (Tail-toTail) Type XVIII - 6,7\8M2-6\7 + ,l 2(11-11) Secolucidine(393)[117J (R,S) Dinklacorine (114)[256-258] Nortiliacorine A (115)[385,391] Tiliacorine(118)[257,391,393,397,398] (S,R) Medelline (318)[348] (S,S) Nortiliacorinine A (116)[257,275,391-398] Nortiliacorinine B (117)[393] Pachyovatamine (250)[357] Tiliacorinine(119)[275,393,396-398] Tiliacorinine-2'-N-Oxide (254)[385] Yanangcorinine (388)[398] Type XIX - 5,6,7\8\12-6\7\12(11-11) (R,S) Norisoyanangine (335)[385] (S,S) N-Methyltiliamosine (323)[381,382] Ti!iamosine(120)[356,357,382,392] Noryanangine (346)[385] Tilianangine (386)[257] Yanangine (389)[258] Unknown stereochemistry N-Methylpachygonamine (243)[356,357] Pachygonamine (249)[356,357] Type XlXa - 5,7\8M2-6\7%12(11-11) Tiliaresine (429)[382]

P.L.SchifT,Jr. Table 6. Continued VIII. One Diphenyl Ether Linkage (Head-to-Tail) and One Benzylphenyl Ether Linkage (Head-to-Tail) Type XXII - 6,7\8,12+-6,7,8*[7-121 Cissampareine (145)[149] Dimethylwarifteine (148)[251] Methylwarifteine (150)[251] Warifteine(151)[251] Dihydrowarifteine (146)[251] Dimethyldihydrowarifteine (147)[251 ] Methyldihyhdrowarifteine (149)[251 ] (R,R) (-)-Cycleaneonine (403)[188] Isocycleaneonine (412)[188] Unknown stereochemistry (+)-Cycleaneonine (286)[ 187,188] Type XXIIa - 6,7,8,11 \12-6,7\12[7-121 Cycleatjehenine (404)[211,212] Cycleatjehine(405)[211] Unknown stereochemistry Cissampentin (395)[150] IX.

Two Diphenyl Ether Linkages (Head-to-Head) and One Diphenyl Ether Linkage (Tail-to-Tail) Type XXIII - 6\7\ll",12-6 f 7\8\12~ Trigilletimine (162)[ 167,468] 1,2-Dehydromicranthine (154)[234]


163

Table 6. Continued

(-,S) 1,2-DehydroapateIine (193)[11-13,28,34,139.154] 1.2-Dehydro-2'-Nortelobine (292)[233] 1,2-Dehydrotelobine (194)[ 11 -13,16,135,154,235] Gilgitine (261)[68] Kurramine(237)[139] O-Methyldeoxopunjabine (263)[248] O-Methylpunjabine (264)[248,358] Punjabine (265)[68] Secojollyanine (433)[358] (R,R) N,0-Dimethylmicranthine (156)[234,255] 0-Methylmicranthine(158)[234,255] Micranthine (159)[27,234,255] (*,S) Apateline(l87)[9-13] N-Methylapateline (207)[336] N-Methylnorapateline (208)[336] 2-N-Methyltelobine (418)[135] Telobine(160)[l 1,119,255] (S,S) Cocsoline(152)[9,10,16,139,153-158] Cocsoline-2'P-N-Oxide (398)[159] Cocsuline(153)[7,9,10,16,139,153,155-158.160.161.165-170] Cocsuline-N-2-Oxide (231)[171] 12-O-Demethyltrilobine (155)[165](designated by the nortrilobine)[153] Isotriiobine(157)[7,13,16,139,153.216,235.329-335] O-Methylcocsoline (239)[ 10,13,16] 12-0-MethylcocsoIine-2'-P-N-Oxide (4I4)[159] 12-O-Methyltricordatine (419)[7] 2'-Norcocsoline (421)[159] 2'-Norcocsuline (329)[7,10] Nortrilobine (247)[399] Tricordatine (161)[7,139,169] Trilobine(163)[ 153,154,165,216,235,329-333,399,469]

authors

as

1^4

P.L. Schiff, Table 6. Continued Type XXIIIa - 5,6/7\8M2~-6\7M 1~,12 1,2-Dehydrokohatamine (289)[233] 1,2-Dehydrokohatine (290)[233] Siddiquamine (371)[233] Siddiquine (372)[233] (S,R) 5-Hydroxyapateline (309)[233] 5-Hydroxytelobine (310)[233] (S,S) Kohatamine (314)[233] Kohatine (236)[ 139,233] Type XXIV - 6,7\8\11~,12-6,7\8\12~ Menisarine (165)[332,349] Normenisarine (166)[216] (5,5) Cocsiline(396)[153] Cocsilinine(397)[153] Cocsulinine(164)[153,156] Gilletine(202)[280,281] O-Methylcocsulinine (415)[153] N-Norcocsulinine (422)[153] Unknown stereochemistry Isogilletine-N-Oxide (204)[281] Pendilinine(425)[153] Type XXVHI - 6 , 7 # f 8 \ l l 4 M M V \ 1 2 ~ (SfS) Angchibangkine (394)[7]

X.

One Diphenyl Ether Linkage plus One Benzyl Phenyl Ether Linkage (Head-to-Head) and One Diphenyl Ether Linkage (Tail-to-Tail) Type XXV - 6,7,8\H\12,13-6,7\12*[8-61 Unknown Pseudorepanduline (167)[234] Repanduline (168)[27,426]


165

Table 6. Continued XI.

One Diphenyl Ether Linkage plus One Benzyl Phenyl Ether Linkage (Head-to-Tail) and One Diphenyl Ether Linkage (Head-to-Tail) Type XXVI - 6,7,8\12+-6,7,8M2*|11-7| (RfR) Insulanoiine (169)[ 192,252,308,309] Insularine (170)[ 182,189.192,252,308,310] Insularine-2P-N-Oxide (408)[252] Insularine-2'P-N-Oxide(409)[252]

XII.

Undetermined Structure Dinklageine (172)[259] Himanthine(173)[81] Isochondocurarine (174)[311] (+)-Neochondocurarine (175)[311] Ocodemerine (176)[236] Otocamine (177)[236] Pendine(178)[153,156] Pendulinine(179)[153,156] Protochondocurarine (180)[311] Pycnarrhenamine (181)[100] Pycnarrhenine (182)[100] Tiliacoridine(183)[464] Tiliandrine (184)[314] Tiliarine (185)[395,467] Tomentocurine (186)[141]

8.

ALKALOIDS WITH DUPLICATIVE OR ERRONEOUS NOMENCLATURE

It is natural that over the years, a number of alkaloids that were believed to be novel and were being reported in the literature for the first time, were in fact not so. This most commonly happened when two groups submitted manuscripts for publication at approximately the same time. It can occur for other reasons, but notwithstanding these, it is important to include a section in this chapter dealing with duplicative or erroneous nomenclature. The following table and paragraphs are an attempt to summarize those alkaloids that have been subject to some confusion in nomenclature.

166

P.L. SchifT,Jr. Table 7: Alkaloids with Duplicative Nomenclature

Alkaloid First Literature Citation (Year)

Alkaloid Subsequent Literature Citation(s) (Year)

Aromoline (31)[478](1949)

Thalicrine (31)[40,471](1963)

Hernandezine (81)[293](1962)

Thalicsimine (Thaliximine) (81)[284,285] (1964)

Cocsuline(153)[166](1970)

Efirine (153)[170](1973), Trigilletine [169](153)(1973), N-Methyl-12'-0Desmethyltrilobine (153)[ 165]( 1972)

12-O-Demethyltrilobine (155) [165](1972)

2'-Norcocsuline (329)[10](1987)

Cycleapeltine (36)[43](1973)

Faralaotrine (36)[209](1975)

Guattegaumerine (234)[254] (September, 1983)(received November 15, 1982)

N,N'-Dimethyllindoldhamine (234)[231 ] (September, 1983Xreceived January 16, 1983)

2'-Nordaurisoline (330)[230] (July, 1987)(revised received October 1, 1986)

Pampulhamine (352)[279](September, 1987) (received March 16, 1987)

Dehatridine (287)[232](February, 1989)(received February 16,1988)

Stepierrine (376)[34](July, 1989) (received October 10, 1988)

Thalisopine (54) was first isolated from Thalictrum isopyroides C.A.M. (Ranunculaceae) in 1961 [471,482]. Some five years later, a detailed spectral analysis of the alkaloid resulted in its structural assignment as 54 [471]. However, it was not until 1978 that the structure of thalisopine was settled with certainity. At that time, extracts of Thalictrum rugosum Ait. (Ranunculaceae) furnished an alkaloid that was named thaligosine, but was later found to be identical with thalisopine [471]. It is therefore logical that the earlier name of thalisopine take precedent over thaligosine.

The bisbenzylisoquinoline Alkaloids - A Tabular Review

167

O-Methylthalicberine (95) was first isolated from Thalictrum thunbergii DC. [also known as T minus var. hypolecum (Ranunculaceae)] in 1959 [378] and its structure determined in the next decade [471]. The alkaloid thalmidine (95), first isolated from Thalictrum minus L. (Ranunculaceae) in 1950 [366] and later in 1956 [367], was shown to be identical with Omethylthalicberine in 1965 [479,480]. When the structure of thalicrine (31)[40,471] was revised to that of the hitherto known aromoline (31)[478], this resulted in the reassignment of homothalicrine (42) as homoaromoline (42)[40,41]. Homothalicrine had first been isolated in 1962 [40]. Thalrugosamine (42) was isolated in 1972, but a reevaluation of its structural assignment in 1984 demonstrated that thalrugosamine was identical with homoaromoline (42)[38]. Thalfoetidine (99) wasfirstisolated from Thalictrum foetidum L. (Ranunculaceae) in 1966 [108,481]. An alkaloid first named thalictrinine was isolated from Thalictrum longipedunculatum E. Nik. (Ranunculaceae) in 1968, but was later found to be identical with thalifoetidine (99)[471]. It is particularly important that this distinction be understood, because an alkaloid designated thalictrinine (220), and of different structure, was isolated from Thalictrum rochebrunianum Franc, and Sav. in 1980 [250]. Thalisamine was first isolated from Thalictrum simplex L. (Ranunculaceae) in 1967, and assigned as N-norhernandezine [296]. It was not until 1984 that Guinaudeau et al. [38] called attention to the close resemblance between thalisamine and N'-norhernandezine (212), the latter being isolated from Thalictrum rochebrunianum Franc, and Sav. in 1980 [250]. It was eventually concluded that the two alkaloids were identical. When the structure of cissampareine (145) was verified by X-ray crystallographic determination in 1978 [477], it was established that the compound known as methylwarifteine (150) was actually cissampareine. Finally, it should be noted that the prefix "nor-" has been erroneously used on several occasions. This prefix is traditionally employed in alkaloid chemistry to designate a lower homologue differing from the parent alkaloid in the loss of a N-methyl group ("N ohne Radikal")[184]. Within the bisbenzylisoquinoline alkaloid series, this prefix almost always suggests the loss of a N-methyl group from Ring B or Ring B\ with the generation of a secondary amine function (R,NH). However, this prefix has also been used to designated the loss of an O-methyl group (with a phenol usually resulting). There are no less than forty-six bisbenzylisoquinoline alkaloids that employ the prefix "nor-" (see Table 1). Five of these alkaloids use the prefix "nor-" to designate the loss of a methyl function from a methoxy group, thereby leaving a phenol. These five alkaloids are: (+)-norcycleanine (124), (-)-norcycleanine (125), normenisarine (166), (+)-nortenuipine (88), and (-)-nortenuipine (89).

168 9.

P.L.Schiff,Jr. AN ANALYSIS OF THE DISTRIBUTION OF THE BISBENZYLISOQUINOLINE ALKALOIDS BY STRUCTURAL TYPE

It is appropriate to present a few qualifying statements that pertain to the nomenclature used in the following analysis. First, when the terms "head" and "tail" are used, they refer to the isoquinoline portion and the benzyl portion, respectively, of the benzylisoquinoline ring. Second, the paired chiral centers that are designated refer to the C(l) and C(l') carbon atoms, respectively. Third, if in place of the term "JT or "5" when designating these centers there is a "-", then this indicates that the chirality of the carbon atom involved has been lost (likely due to the formation of an imine bond). Fourth, as stated in the Introduction, the alkaloids have been drawn such that the Ring C terminus of the diphenyl ether bridge between Ring C and Ring C is always at C-12'. In addition, the alkaloid numbering system and structural-type nomenclature generally follow those of earlier reviews in this series [1-5]. Fifth, there are very few references that are included as citations in the following analysis, because all of the conclusions presented have been drawn from the fully referenced tables in this chapter. Finally, the analysis that follows is consistent with the order in which the bisbenzylisoquinoline alkaloids are described by structural type in Table 6.

9.1.

One Diphenyl Ether Linkage (Tail-to-Tail)

The alkaloids of Types I, la, lb, II, Ila, lib, and III contain one diphenyl ether linkage and are linked tail-to-tail. There are no alkaloids in this group that are imines, with only a few secondary amines being found. 9.1.1. Type I (6,7,11\12-6,7,12#) (R,R) Alkaloids The largest subgroup (26 alkaloids) within Type I are those alkaloids with R,R stereochemistry at the C( 1) and C( 1') carbon atoms, respectively. There are seventeen alkaloids that are bis N-methyl compounds within this group. One of these alkaloids [O-Methyldauricine (12a)] is fully methylated at the available ether oxygen atoms [C(6), C(7), C(12), C(6'), C-(7')], while six of the alkaloids are monophenolic, seven are biphenolic, and three are triphenolic. The most common position that contains a phenolic group is C(12)(eight alkaloids), while the least common is C(6')(four alkaloids). There are three alkaloids that are secondary amines at N(2'), with each of these compounds having methoxy groups at C(6) and C(6') and phenolic hydroxy groups at C(12). Two of the three alkaloids are phenolic at C(7), while only one is phenolic at C(7'). 2'-Nordaurisoline (330) and pampulhamine (352) are identical, with both being published the same year and at about the same time [230,279]. However, since the former was received on October 1, 1986 and the latter on March 16, 1987, it is probably appropriate to use the former (2'-Nordaurisoline) as the official title of the alkaloid. There are four alkaloids that are bissecondary amines, and all of these compounds have methyl ethers at both C(6) and C(6'). Three of the alkaloids are phenolic at either C(7) or C(7'), with two of the compounds being biphenolic at these positions. It can be concluded that when bis secondary alkaloids are found within this

The Misbenzylisoquinoline Alkaloids - A tabular Kevlew

169

group, phenols when present are most commonly found at one or more of C(7)/C(7')/C(12). There are only two N-oxides within this group, and there are no alkaloids with unsaturation in the A or A' rings. The families Annonaceae (sixteen alkaloids) and Menispermaceae (fifteen alkaloids) are the most fruitful sources of these alkaloids, with the genera Popowia (ten alkaloids)(Annonaceae) and Menispermum (nine alkaloids)(Menispermaceae) being the most productive genera. The following is indicative of the distribution of alkaloids within these and other families: Annonaceae (Popowia - ten; Polyalthia - four; Cardiopetalum - one; Guatteha one); Menispermaceae (Menispermum - nine; Abuta - five; Albertisia - one; Caryomene - one); Aristolochiaceae (four)(all Aristolochia sp.); Berberidaceae (one)(Berberis sp.); Rhamnaceae (one)(Colubrina sp.).

H 3

47

9.5.2. Type Via (6,7\10,H\12-6,7,8\12*) There is only one alkaloid in this group, (S,/?)-osornine (248), from Berberis bwcifolia (Berberidaceae). The substitution in Ring C is unusual due to the presence of C(10) oxygenation.

v

OCH 3 248


203

9.5.3. Type VII (6,7\11\12-5,6,7,8\12 + ) There are three parent alkaloids in this group, thalisopine (54)(thaligosine), thalisopidine (53) and thalrugosaminine (55), as well as the 2o>N-oxides of thalisopine and thalrugosaminine. The three parent alkaloids share the following characteristics: bis N-methylation, methoxylation at C(6), C(6), and C(7'). The compounds differ only in their potential phenolic nature at C(12) and C(5'). The five alkaloids of this group bear the 5,5 stereochemistry at their nitrogen atoms. These alkaloids have only been isolated from various species of the genus Thalictrum (Ranunculaceae), with thalisopine (54)(thaligosine) having been isolated from ten Thalictrum sp., thalisopidine only from T isopyroides, and thalrugosaminine from seven Thalictrum sp. The two N-oxides, thaligosine-2o>N-oxide [thalisopine-2a-N-oxide] (378) and thalrugosaminine-2a-Noxide (384) have only been isolated from T cultratum.

Alkaloid

E,

Rj

Thalisopine (54) Thalisopidine (53) Thalrugosaminine (55)

CH3 H CH3

H H CH3

Alkaloid

R

Thaligosine-2a-N-Oxide (378) Thalrugosaminine-2a-N-Oxide (384)

H CH3

204

P.L.Schiff,Jr.

9.5.4. Type VIII (6,7,8\11+,12-6,7M2*) (-,-) Alkaloids The sole alkaloid of this type that lacks chirality at both nitrogen atoms is phaeantharine (73), a bisquaternary alkaloid that is a true isoquinoline (not a tetrahydro- or dihydroisoquinoline), and only a metabolite of Phaeanthus ebracteolatus (Menispermaceae).

73 (/?,-) Alkaloids There are three alkaloids in this small subgroup, one of which is the N(2') imine dehatrine (288), and the other two are secobisbenzylisoquinoline derivatives at N(2'). Dehatrine (288), a nonphenolic alkaloid, has been isolated from two Lauraceous species, Beilschmiedia madang and Dehaasia triandra (Lauraceae). Pycmanilline (392) has only been isolated from Pycnarrhena manillensis (Menispermaceae), while secoisotetrandrine (431) has only been found in Laurelia sempervirens (Monimiaceae). These alkaloids differ in the level of oxidation of the carbon that was the methylene bridge and in the non-seco precursor. In the former (pycmanilline), that carbon is a carboxy group, while in the latter (secoisotetrandrine), that carbon is a formyl group. Either isotetrandrine (62) or phaeanthine (74) could have been the precursor of these bases. Only isotetrandrine (62) was reported in Laurelia sempervirens, but both isotetrandrine (62) and phaeanthine (74) were reported as constituents of Pycnarrhena manillensis.

288


205

AlkaloM

E

Pycmanilline (392) Secoisotetrandrine (431)

COOH CHO

(5,-) Alkaloids The secobisbenzylisoquinoline sindamine (270) from Berberis lycium (Berberidaceae) is the only representative of this very small subgroup. The rotation for naturally occurring sindamine was not reported, but sindamine prepared from berbamine had a positive rotation, even though the C( 1) atom of berbamine is of the R stereochemistry.

(-,/?) Alkaloids There are only two alkaloids that constitute this small subgroup, but both bear an identical oxygenation pattern. Berbacolorflammine (218) is monoquaternary benzylisoquinoline at N-2, while caryolivine (281) has a tertiary nitrogen atom in a benzyisoquinoline system. Each alkaloid has only been isolated from a single plant, berbacolorflammine (218) from Pycnarrhena longifolia (Menispermaceae) and caryolivine (281) from Caryomene olivascens (Menispermaceae).

206

PX.Schifr,Jr.

281 (-,S) Alkaloids There are seven alkaloids reported in this subgroup but two of them are identical, being given different names but being reported in the same year (1989): dehatridine (287) from Dehaasia triandra (Lauraceae) and stepierrine (376) from Stephania pierrii (Menispermaceae). The manuscript on dehatridine was received on February 16, 1988 and published in a February, 1989 journal [232]; while the manuscript on stepierrine was received on October 10, 1988 and published in a July, 1989 journal [34]. Dehatridine/stepierrine is a benzylisoquinolinebenzyltetrahydroisoquinoline dimer. Another benzylisoquinoline-benzyltetrahydroisoquinoline dimer is fenfangjine D (1,3,4-tridehydrofangchinolinium hydroxide)(300), which is fangchinolinelike N-2 quaternary alkaloid isolated from Stephania tetrandra (Menispermaceae). Tiliafunimine (79a) is an N-2 imine alkaloid (3,4-dihydrobenzylisoquinoline) isolated from Tiliacora fimifera (Menispermaceae). Possible precursors of tiliafunimine include fangchinoline (61) and cycleadrine (58), but neither of these compounds have been isolated from any of the Tiliacora species. However, both of these compounds have been isolated from genera of the Menispermaceae. Cheratamine (228) is a N-2 imine (3,4-dihydrobenzylisoquinoline) with a carbonyl group at the C-a carbon. It is the only alkaloid of its type and was isolated from Cocculus pendulus (Menispermaceae). The final two alkaloids of this subgroup are

The Misbenzylisoquinollne Alkaloids - A Tabular Review

207

secobisbenzylisoquinoline compounds, chenabine (258) and jheulmine (262), both being metabolites of Berberis lycium (Berberidaceae). These two alkaloids are unusual in that they lack the usual carbonyl group at C(l), instead simply possessing a simple methylene group. Both of the alkaloids have a formyl group at what would be the C(a) carbon, and both are methoxylated at C(6) and C(6'), with a phenolic group at what would be the C(12). Chenabine is methoxylated at C(7), while jheulmine is phenolic at C(12). All of the alkaloids in this subgroup are methoxylated at C(6) and C(6'), with varying degrees of methoxylation at C(7) and C(12). It can easily be observed that most of the alkaloids of this subgroup are from genera of the Menispermaceae and Berberidaceae.

79a

P.L. Schiff,Jr.

AMMd

E

Chcnabinc (258) Jhelumine (262)

CH3 H

(R,R) Alkaloids There are twelve alkaloids that possess the (R9R) stereochemistry, eight of which constitute a subgroup with characteristics to be discussed in the following paragraph. There is one bis secondary amine, 2,2'-bisnorphaeanthine (278), a metabolite of Albertisia papauana (Menispermaceae). There is one N-2 secondary amine, 2-norlimacine (336) from both Anisocycla jollyana (Menispermaceae) and Caryomene olivascens (Menispermaceae) and one N-2' secondary amine, 2'-Norlmacine from Anisocycla jollyana (Menispermaceae) and Cyclea barbata (Menispermaceae). Only one of the eight alkaloids is phenolic at C(6), gyroamericine (305) from Gyrocarpus americanus (Hernandiaceae). Three of the eight alkaloids are monophenolic at C(7), with one being monophenolic at C(12), and another being bisphenolic at both C(7) and C(12). Genera and families represented by the three phenolic alkaloids of this subgroup include: Gyroamericine (305) - Gyrocarpus sp. (Hernandiaceae); Krukovine (63)- Abuta, Curarea, Pycnarrhena (all Menispermaceae); Limacine (64) - Anisocycla, Arcangelisia, Curarea, Cyclea, Limacia, Phaeanthus, Pycnarrhena, Spirospermum (all Menispermaceae); Colubrina (Rhamnaceae); and Gyrocarpus (Hernandiaceae). It can be readily observed that these alkaloids are almost always methoxylated at C(6) and C(6), tend to occur in various Menispermaceous species, and that no imine nor benzylisoquinoline-benzyltetrahydroisoquinoline dimers of this subgroup have been isolated.

The Blsbenzylisoquinollne Alkaloids - A Tabular Review

209

Alkaloid

R,

Kj

R3

2,2'-Bisnorphaeanthine (278) 2-Norlimacine (336) 2'-Norlimacine (423)

H H CH3

CH3 H H

H CH3 H

HCHJ

Alkaloid

R,

R2

R3

Gyroamcricine (305) Krukovinc (63) Limacine (64) Phaeanthine (74) Pycnaminc (75)

H CH3 CH3 CH3 CH3

CH3 H H CH3 CH3

CH3 H CH3 CH3 H

The remaining four alkaloids that possess the (RfR) stereochemistry are mono-N-oxides, three of which are limacine derivatives: limacine-2'a-N-oxide (315) from Curarea candicans (Menispermaceae); limacine-2P-N-oxide (316) from Curarea candicans (Menispermaceae); limacine-2'P-N-oxide (317) from Curarea candicans (Menispermaceae) and Anisocycla jollyana (Menispermaceae). The fourth is phaeanthine-2'a-N-oxide (356) from Pycnarrhena manillensis (Menispermaceae). Thus, only two genera of the Menispermaceae are the source of the N-oxides of this small subgroup.

210

P.L.SchlfT,Jr. ,OCH3

CHjO,

Alkaloid

R

Limacine-2'a-N-Oxide (315) Phacanthine-2'a-N-Oxide (356)

H CH,

,OCH3 H

CHjO,

3Cv "CHj

,OCH3

CHjO,

317


211

(S,S) Alkaloids There are fourteen alkaloids that belong to this subgroup, and none of these compounds are N-oxides or quaternary bases. Three of the seven alkaloids are monosecondary amines, two at N(2) and one at N(2'). AH of the seven alkaloids are methoxylated at C(6), while six are methoxylated at C(6'), the lone exception being atherospermoline (56) which is phenolic at C(6') and has been isolated from Atherosperma moschatum (Monimiaceae) and Pachygone dasycarpa (Menispermaceae). Six of the seven alkaloids are methoxylated at C(7), with the lone exception being fangchinoline (61) which is phenolic at that position and which has been isolated from species of the following families/genera: Menispermaceae - Cyclea, Pachygone, Stephania, Strychnopsis, and Triclisia; Monimiaceae - Daphnandra. Three of the seven alkaloids are phenolic at C( 12), including atherospermoline (56)fromAtherosperma moschatum (Monimiaceae) and Pachygone dasycarpa (Menispermaceae); norpenduline (246) from Cocculus pendulus (Menispermaceae); and penduline (72) from the following families/genera: Euphorbiaceae Andrachne; Berberidaceae - Berberis; and Menispermaceae - Cocculus, Pachygone. Three of the fourteen alkaloids are quaternary at N(2), including cycleahomine (59) from Cyclea peltata (Menispermaceae) and 2-N-Methylfangchinoline (416) from Stephania tetrandra (Menispermaceae). These two compounds differ by having a C(7) methoxy versus a C(7) phenolic hydroxy, respectively. The third alkaloid, monomethyltetrandrinium (67) from Cyclea barbata (Menispermaceae), is not completely characterized, because the position of the quaternary nitrogen atom is uncertain, being either N(2) or N(2'). Four of the fourteen alkaloids are monoN-oxides, with three of the four alkaloids bearing the N-oxide in the N(2') position. The only alkaloid with the N-oxide in the N-2 position is fenfangjine A (tetrandrine-2p-N-Oxide)(297), a compound isolated from Stephania tetrandra (Menispermaceae). Fenfangjine B (fangchinoline2'ct-N-Oxide)(298) and fenfangjine C (fangchinoIine-2'P-N-Oxide)(299) are also metabolites of Stephania tetrandra (Menispermaceae). The fourth alkaloid, tetrandrine mono-N-2'-oxide, does not have the stereochemistry of the oxide described, but was isolated from Cyclea barbata (Menispermaceae). Genera of the family Menispermaceae clearly dominate in the overall distribution of most of the 5,5 alkaloids of type VIII.

Alkaloid

£,

fc

&

Atherospermoline (56) Fangchinoline (61) Penduline (72) (+)-Tetrandrine (76)

CH3 H CH3 CH3

H CH3 H CH3

H CH3 CH3 CH3

212

P.L.Schifr,Jr. ÔCH3 H3C

90

„OCH3

CHaO^

R3

Alkaloid

E,

E2

E3

7-O-Demethylpeinamine (60) Norpenduline (246) 2-Nortctrandrinc (70)

CH, H H

CH3 H CH3

H CH, CH,

„OCH3

CH 3 0 >

Alkaloid

E

Cyclcahominc (59) 2-N-Methylfangchinolinc (416)

CH3 H

The Bisbenzylisoqnlnoline Alkaloids • A Tabular Review

213

„OCH3

CH3Ox

H3CV

,CH 3 ^2

Alkaloid

E,

Monomethyltetrandrinium (67)

H

CH3 or

CH3

H

78

OCH,

CHjO,

H3O1

^

297

214

P.L.SchlfT,Jr.

299 (R,S) Alkaloids There are thirteen alkaloids in this group, none of which are N-oxides or quaternary compounds. All of these alkaloids are methoxylated at C(6'). It can be observed that whichever side bears a C(7) phenylether bridge, the substituent at C(6) will be a methoxyl group. Eleven of the thirteen alkaloids are methoxylated at C-6 (two phenols), while only 7 are methoxylated at C(7) (six phenols). Seven of the thirteen alkaloids are methoxylated at C(12), with the remainder being phenolic. There are seven alkaloids that have one or two secondary nitrogen atoms. Four of these alkaloids are secondary at N(2) but tertiary at N(2'), while only one alkaloid is secondary at N(2') but tertiary at N(2) [nor-2'-isotetrandrine (213) from Limaciopsis loangensis (Menispermaceae) and Stephania pierrii (Menispermaceae)]. There are two alkaloids that are bis secondary compounds, bisnorobamegine (277) and bisnorthalrugosine (279), both having been isolated from Pycnarrhena ozantha (Menispermaceae). There are two alkaloids that are quaternary at N(2'): 2'-N-methylberbamine (66a) from Berberis oblonga and Berberis turcomanica (Berberidaceae), and N-2'-methylisotetrandrine from Berberis oblonga (Berberidaceae). Finally there are two N-oxide alkaloids: berbamine-2'P-NOxide (274) from Berberis brandisiana (Berberidaceae) and N-oxy-2'-isotetrandrine (216) from Limaciopsis loangensis (Menispermaceae).

215

The Blsbenzylisoquinoline Alkaloids - A Tabular Review .OR, H3C

v

H"'

CH 3 0 N .N.

OR2

ST'-H

ÔR3 Alkaloid

E,

E2

E3

Aquifoline (273) Berbamine (57) Cycleabarbatine (402) Isotetrandrine (62) Obamegine (71) Thalrugosine (79)

H CH3 H CH3 CH3 CH3

CH3 CH3 CH3 CH3 H H

H H CH3 CH3 H CH3

Alkaloid

Ei

E2

E3

Bisnorobamegine (277) Bisnorthalrugosine (279)

CH3 CH3

H H

H CH3

XH3

216

P.L.Schifr,Jr. CH 3 0 N

W "H

Alkaloid

E,

2-N-Norberbamine (68) 2-Norisotetrandrine (334) 2-N-Norobamegine (69) 2-Northalrugosine (344)

CH, CH, CH, CH3

ÔCH3

E3 CH3 CH3 H H

H CH, H CH3

CH3ON

213

ÔCH3

CH 3 0 N

Aikajojd 2-N'-Methylbcrbaminc (66a) N-2'-Methylisotetrandrine (319)

H CH3

TH3

The Blsbenzylisoquinoline Alkaloids - A Tabular Review

217

(StR) Alkaloids There are only three alkaloids in this small subgroup, and all are derivatives of the monophenolic [C(12)j, monosecondary [N(2)] alkaloid peinamine (71a) which has only been isolated from A buta grisebachii (Menispermaceae). The other two alkaloids are 7-0demethylpeinamine (60a) and N-methyl-7-O-demethylpeinamime (66b), both being metabolites of the same plant as above. In addition, the latter has been isolated from Pachygone dasycarpa (Menispermaceae).

71a

218

P.L.SchifT,Jr.

66b Miscellaneous alkaloids

There are two alkaloids that are racemic mixtures: cycleadrine (58) [(+/-) - fangchinoline] from Cyclea barbata and C. peltata (Menispermaceae) and (+/-)-tetrandrine (77) from the same two plants, as well as from Isopyrum thalictroides (Ranunculaceae) and Stephania hernandifolia (Menispermaceae). Menisidine (65) is likely a fangchinoline isomer and menisine (66) is likely a (+)-tetrandrine stereoisomer. These latter two alkaloids were isolated from Stephania tetrandra (Menispermaceae). Oxofangchirine (349) is a benzyltetrahydoisoquinoline-benzylisoquinolone alkaloid from Stephania tetrandra (Menispermaceae). The stereochemistry at C( 1) is not defined.

58


219 CH^

OCH3

XH3

77 „OCH3

CH3ON

T>CH3 65

CfyO,

„OCH3

TH3

"OCH3 66 CH^

OCH3

^ OCH3 349

220

P.L.Schifr,Jr.

9.5.5. Type IX (5,6,7,8MlM2-6,7\l2+) (£,-) Alkaloids The only two alkaloids of this very small subgroup are thalsimidine (85), which has only been isolated from Thalictrum simplex (Ranunculaceae), and thalsimine (86), an alkaloid that has been isolated from three species of Thalictrum (T rochebrunianum, T rugosum, and T simplex). Thalsimine (86) is actually a 1:1 mixture of the two conformers of 5-O-methylthalsimidine.

Alkaloid

R

Thalsimidine (85) H Thalsimine (86) CH3 (a 1:1 mixture of the two conformers of 5-O-MethyIthalsimidine)

(S,S) Alkaloids There are four alkaloids and one alkaloid-N-oxide that constitute this subgroup. All of these alkaloids are methoxylated at C(6), C(7), C(12), and C(6'). Three of the five compounds are monosecondary amines, one at N(2) and two at N(2'). Two of the alkaloids are phenolic at C(4), while the other three are methoxylated at that position. N-Desmethylthalidezine (80) has only been isolated from Thalictrum podocarpum (Ranunculaceae), while thalidezine (83) has been isolated from nine different Thalictrum species, including T podocarpum. Hernandezine (5-0methylthalidezine)(81) has been isolated from twelve different Thalictrum species (including T. podocarpum) as well as one other plant, Cocculus pendulus (Menispermaceae). Thalisamine (84) was subsequently shown to be identical with N'-norhernandezine (212). These alkaloids have been isolated from T simplex and T rochebrunianum, respectively. Hernandezine-N-oxide (203) has only been isolated from T sultanabadense (Ranunculaceae).

221


*R3

v

OCH3

Alkaloid

R,

E±2

*±3

N-Desmethylthalidezine (80) Hernandezine (81) Thalidezine (83) Thalisamine (84) [also called N'-Norhernandezine (212)]

H CH 3 CH 3 CH 3

H CH 3 H CH 3

CH3 C.H3 CH 3 H

OCH3

H3C

203 (S,R) Alkaloids Isothalidezine (82) is the only bisbenzylisoquinoline alkaloid of this group with the S,R stereochemistry that has been isolated from nature. This alkaloid was found in Thalictrum delavyi, T. glandulosissimum, and T. podocarpum (Ranunculaceae). Epinorhernandezine (199) is a semisynthetic product. With but one exception, all of the sources of the nine alkaloids of Type IX are Thalictrum species.

222

P.L.Schiff,Jr.

Alkaloid

R

Isothalidezine (82) Epinorhernandezine (199)

H CH3

9.5.6. Type X (6,7,8\ll\l2,13-6,7*42*) (R,R) Alkaloids There are two alkaloids that constitute this very small subgroup. (-)-Nortenuipine (89) has only been isolated from Daphnandra tenuipes (Monimiaceae), while (-)-tenuipine (92) has been isolated from both Daphnandra tenuipes and D. dielsii (Monimiaceae). The "nor" designation is misleading with regard to nortenuipine, because this prefix is usually reserved for secondary amines, but in this case refers to C(7) position which is phenolic in nortenuipine and methoxylated in tenuipine.

Alkajojd

R

(-)-Nortenuipine (89) (-)-Tcnuipine (92)

H CH3


223

(S,S) Alkaloids As with the (5,5) alkaloids, there are only two alkaloids in this subgroup; (+)-nortenuipine (88) from Daphnandra johnsonii, D. tenuipes, and Daphnandra species Dt-7 (Monimiaceae); and (+)-tenuipine (91) from Daphnandra tenuipes (Monimiaceae) and an unnamed Daphnandra species. The same misleading use of the prefix "nor" applies to (+)-nortenuipine as did to (-)nortenuipine above.

Alkaloid

£

(+)-Nortenuipine (88) (+)-Tenuipine (91)

H CH3

(R,S) Alkaloid The sole alkaloid of this stereochemical subgroup is isotenuipine (87), an alkaloid of a Daphnandra species (Monimiaceae).

224

P.L. Schiff, Jr.

Racemic Alkaloid There is only one racemic alkaloid in the type X alkaloid group. Repandinine [(+/-)tenuipine](90) has been isolated from four Daphnandra species, including D. dielsii, D. johnsonii, D. repandula, and D. tenuipes. It can be concluded that the alkaloids of this type are fundamentally of two groups; the nortenuipine (7-demethyltenuipine) type and the tenuipine type, each with differing stereochemistry. The C(12)/C(13) methylenedioxy group in these alkaloids is unusual in its occurrence, particularly within the bisbenzylisoquinoline alkaloids. The alkaloids of this group are restricted to the genus Daphnandra (Monimiaceae). 9.5.7. Type Xa (6,7,8M0,11M2-6,7*, 12*) These alkaloids are very unusual, in that they possess oxygenation at C(10). In each case, this oxygenation takes the form of a methoxyl group. (5,-) Alkaloids Calafatimine (189) is a nonphenolic N(2') imine alkaloid that has only been isolated from Berberis buxifolia (Berberidaceae). Curacautine (259) and talcamine (271) are two secobisbenzylisoquinoline alkaloids that have been isolated from the same plant and that contain ring B' in a higher oxidation state are. The ring C constituent in the former is a formyl group, while in the latter it is a carboxymethyl.

189

The Bisbenzylisoquinoline Alkaloids - A Tabular Review „OCH3

225

CH3Ox

Alkaloid

R

Curacautine (259) Talcamine (271)

CHO COOCH3

(S,R) Alkaloids Calafatine (190), the parent alkaloid of this small subgroup, has only been isolated from two Berberis species, B. buxifolia and B. horrida (Berberidaceae). The two N-oxides of calafatine, 2'ot (226) and 2'p (227), have only been isolated from Berberis buxifolia (Berberidaceae). „OCH3

CH 3 O v

190

„OCH3

CH 3 0^

ÔCH3 Alkaloid Calafatine-2'ct-N-Oxide (226) Calafatine-2'P-N-Oxide (227)

R2 O* CH3

CH3 O

226

P.L.SchifT,Jr.

The alkaloids of this group are restricted to the genus Berberis of the family Berberidaceae. In fact, B. buxifolia has been the source of all the alkaloids, with B. horrida serving as an additional source of calafatine (190). 9.5.8. Type Xb (6,7\8,10,11*,12,13-6,7*, 12*) Daphnine (191), the highly conjugated N(2) zwitterionic alkaloid from Daphnandra dielsii and D. repandula (Monimiaceae), is the sole representative of this type of alkaloid. Daphnine is of very restricted distribution to the genus Daphnandra.

191

9.5.9. Type XI (6,7,8\11M2-6\7,12 + ) (5,-) Alkaloids There are four alkaloids that constitute this small subgroup. The mono imine [N(2')] alkaloids thalmethine (98) and O-methylthalmethine (96) have only been isolated from Thalictrum species (Ranunculaceae), with the former reported as a constituent of T. minus, while the latter has been found in T minus, T minus var. minus, and T revolutum. These two alkaloids differ at C(12), where thalmethine is monophenolic. A third N(2') imine alkaloid is thalsivasine (380), a constituent of Thalictrum cultratum and Thalictrum minus var. minus. This alkaloid is monophenolic at C(7), instead of C(12). The final alkaloid of this small group is the secobisbenzylisoquinoline alkaloid revolutionone (266) which has only been isolated from Thalictrum revolutum (Ranunculaceae). The alkaloids of this small subgroup appear to be restricted in distribution to the genus Thalictrum.

227


Alkaloid

R,

R2

O-Methylthalmethine (96) Thalmethine (98) Thalsivasine (385)

CH3 CH3 H

CH3 H CH3

266 (5,5) Alkaloids The six alkaloids of this subgroup differ in their substitution at C(7), C(12) and N(2'). In general, different combinations of phenolic and methoxyl groups vary at C(7) and C(12), with only one alkaloid of the group being a secondary amine at N(2'). Thalicberine (97) and O-methylthalicberine (95) differ in that the former is phenolic at C( 12). Thalicberine has been isolated from four species of Thalictrum, and from an additional three varieties of one of these species (T minus). This accounts for seven separate isolations of this alkaloid from species and varieties of the genus Thalictrum. O-Methylthalicberine (95) has been isolated from no less than ten species of this same genus, as well as an additional four varieties of one of these species (T minus). However, the latter has also been isolated from two species of the genus Berbehs (Berberidaceae). There are three alkaloids of the thaliphylline (253)-type that have been described: thaliphylline (253) from Thalictrum cultratum and two varieties of Thalictrum minus; 2'northaliphylline (342) from T cultratum; and thaliphylline-2'P-N-Oxide (379) also from T cultratum. The thaliphylline-type alkaloids are phenolic at C(7).

228

PL.Schiff,Jr.

The final alkaloid of this type is thalivarmine (380), an alkaloid that is bisphenolic at C(7) and C(12), having been isolated from only one plant, Thalictrum minus L. var. minus. It can be easily concluded that the alkaloids of this small subgroup are almost entirely restricted in distribution to the genus Thalictrum.

^3

Alkaloid

E,

O-Methylthalicberine (95) 2'-Northaliphylline (342) Thalicberine (97) Thaliphylline (253) Thalivarmine (380)

CH3 H CH3 H H

E3 CH3 CH3 H CH3 H

CH3 H CH3 CH3 CH3

«CH3

ÔCHj 379


229

(R,S) Alkaloids The four alkaloids of this subgroup differ only in their substitution at C(7) and C(12). There are no nor-alkaloids in the series. The fully methoxylated alkaloid of the subgroup is Omethylisothalicberine (94), a compound that has only been isolated from two species of the genus Berberis (B. chilensis and B. laurina) (Berberidaceae). Monophenolic relatives of this alkaloid are belarine (93)[C(7) phenol] and isothalicberine [C(12) phenol], the former of which has only been isolated from Berberis laurina (Berberidaceae) while the latter has only been found as a metabolite of B. chilensis. Finally, the bisphenolic [C(7) and C(12)] alkaloid 7-0demethylisothalicberine (195) has been found in Berberis chilensis and B. laurina. It can be concluded that the alkaloids of this small subgroup appear to be restricted in their distribution to just two species of the genus Berberis (B. chilensis and B. laurina)( Berberidaceae).

Alkaloid

R,

R2

Belarine (93) 7-O-Demethylisothalicberine (195) Isothalicberine (205) O-Methylisothalicberine (94)

H H CH3 CH3

CH3 H H CH3

9.5.10. Type XII (6,7,8\llM2-5\6,7,12+) (S,S) Alkaloids All of the alkaloids of this group have identical stereochemistry (5,5), and differ only in their substitution at N(2), C(7), and C(12). Two of the alkaloids are secondary amines at N(2), while an additional two are N-formyl derivatives at that position. Four of the nine alkaloids are phenolic at C(7) (the rest being methoxylated), while only two of these alkaloids are phenolic at C(12). One alkaloid is phenolic at both positions [thaligosidine (100a)]. Thalidasine (100) analogs include N-desmethylthalidasine (196) and thalidasine-2o>Noxide (377). Thalidasine has been isolated from no less than fourteen species of the genus Thalictrum (including T. cultratum and T. faberi), while N-desmethylthalidasine (196) has been isolated only from Thalictrum cultratum and T. faberi. The N-oxide has been isolated from just one plant, T. cultratum. Thalrugosinone (224), the N(2)-formyl derivative of thalidasine, has

230

P.L.Schiff,Jr.

been isolated from T cultratum and T. rugosum. The occurrence of thalidasine (the fully methoxylated parent alkaloid of this series) and its analogs appears to be restricted to one genus, Thalictrum (Ranunculaceae). Furthermore, only one species, T cultratum, is the source of all four thalidasine-related alkaloids of this series. Thalrugosidine (101)(7-demethylthalidasine) has been isolated from five species of the genus Thalictrum (including Thalictrum alpinum), while its N(2)-demethyl derivative Ndesmethylthalrugosidine (197) has been isolated from only Thalictrum alpinum. Thalpindione (223), also known as N-2-formylthalrugosidine, is only a metabolite of Thalictrum alpinum. The occurrence of thalrugosidine and its derivatives is restricted to the genus Thalictrum, with all three alkaloids of this small subseries being isolated from just one species, T alpinum. Thalfoetidine (99)(12-demethoxythalidasine) has been isolated from Thalictrum fargesii, T.flavum,and T. longipedunculatum, and has not been isolated from any other source. The fully methoxylated parent alkaloid of this series, thalidasine (100) has also been isolated from these three species. Thaligosidine (100a)(7,12-demethoxythalidasine) has only been found in Thalictrum rugosum. Thalidasine has also been isolated from this species. It can be concluded that the distribution of the nine alkaloids of this Group are entirely restricted to species of the genus Thalictrum (Ranunculaceae).

Alkaloid

E,

£2

N-Desmethylthalidasine (196) N-Desmethylthalrugosidine (197)

CH3 H

CH3 CH3


Alkaloid

Ei

E2

Thalpindione (223) Thalrugosinonc (224)

H CH3

CH3 CH3

Alkaloid

Ei

E2

Thalfoctidinc (99) Thalidasine (100) Thaligosidinc (100a) Thalrugosidine (101)

CH3 CH3 H H

H CH3 H CH3

232

P.L.Schiff,Jr.

9.5.11. (Type Xlla

S&IJ&\\\%l2-f&l,\r)

There are only two alkaloids that comprise Type Xlla, 5-hydroxythalidasine (311) and 5hydroxythalidasine-2a-N-oxide (312). These two bases have the S£ stereochemistry and have only been found to date in Thalictrum cultratum.

312 9.5.12. Type XIII (5\6,7,llM2-5,6,7,8\12*) These alkaloids are somewhat unusual in that both sides bear 5,6,7-oxygenation. (5,5) Alkaloids The fully methoxylated parent alkaloid of this type group thalfinine (103), as well as its 5'-demethyl- analog thalmirabine (222), have both been isolated from just two plants, Thalictrum foetidum and T. minus (Ranunculaceae).


s

233

OCH 3

Alkaloid

R

Thalfinine (103) Thalmirabine (222)

CH3 H

(£,-) Alkaloid Thai fine (102), a benzyltetrahydroisoquinoline-benzylisoquinoline alkaloid, is the ring B' oxidized derivative of thalfinine (103). Thai fine (102) has also only been isolated from Thalictrum foetidum and Thalictrum minus.

H3C

ÔCH3 102

It can be observed that the type XIII alkaloids are a very small group of compounds that are of restricted in distribution to the genus Thalictrum, and specifically within this genus to the species T. foetidum and T. minus.

234

P.L.SchifT,Jr.

9.5.13. Type XIV (6,7*,HM2-5*,6,7,12*) (5,-) Alkaloid Thalmiculatimine (381), isolated from Thalictrum cultraturn, is the only alkaloid of this small subgroup. It is a N-2'-demethyl derivative of thalictine (107), and because of the distribution of the alkaloids in the series to follow, it is most likely to have derived from thalictine (107). There are five different Thalictrum alkaloids in the S,S series, with each of these alkaloids having its distribution restricted to the genus Thalictrum. However, there are only three alkaloids in the S,R series, and only one of these compounds is found in the genus Thalictrum.

381 (RfS) Alkaloids The fully methoxylated parent alkaloid of this subgroup is lauberine (106), which is a metabolite ofBerberis laurina (Berberidaceae). Berbilaurine (275)(6-demethyllauberine) has also only been found in Berberis laurina, but 12-O-desmethyllauberine (294) has only been isolated from Berberis chilensis. It appears that the alkaloids of this small stereochemical subgroup are restricted in distribution to the genus Berberis (Berberidaceae).

Alkaloid

E.

S2

Berbilaurine (275) 12-O-Desmethyllauberine (294) Lauberine (106)

H CH3 CH3

CH3 H CH3


235

(S,R) Alkaloids Dryadine (104) and dryadodaphnine (12-demethyldryadine)( 105) have been isolated from Dryadodaphne novoguineensis (Monimiaceae), while thalifortine (6-Methyldryadodaphnine)(428) has only been isolated from Thaiictrum fortunei (Ranunculaceae).

Alkaloid

R,

R2

Dryadine (104) Dryadodaphnine (105) Thalifortine (428)

H H CH3

CH3 H H

(S,S) Alkaloids The fully methoxylated parent alkaloid of this series is O-methylthalmine (244), an alkaloid that has only been found in Thalictrum cultratum and Thalictrum sultanabadense (Ranunculaceae). The alkaloids in this small subgroup differ in their substitution at N(2), C(12), and C(6'). Thalictine (12-demethyl-O-methylthalmine)(107) has been isolated from three Thalictrum species; T cultratum, T. sultanabadense, and T thunbergii, while thalmine (108) has been isolated from T. cultratum, T. kuhistanicum, and T minus. There are two diphenolic alkaloids with the S,£ stereochemistry; 2-northalmine (343) and thalabadensine (12demethylthalmine)(106a), the former a metabolite of Thalictrum cultratum, while the latter has been found in Thalictrum minus and Thalictrum sultanabadense. It can be concluded that the alkaloids of this small subgroup are restricted in distribution to several species of the Thalictrum genus, with T cultratum and T sultanabadense being the most common sources. An interesting feature that may be observed concerning the distribution of the type XIV alkaloids is the effect of the stereochemistry of the chiral centers. The R,S alkaloids are confined to a single genus (Berberis) of the Berberidaceae, while the S,S alkaloids are similarly restricted to a single genus (Thalictrum) of the Ranunculaceae. The S,R alkaloids are found in both the Monimiaceae (Dryadodaphne) and the Ranunculaceae (Thalictrum). To date, no alkaloids with R,R stereochemistry have been found in nature.

236

P.L.Schlff,Jr.

H3C

Alkaloid

R.

E2

O-Methylthalmine (244) Thalabadensine (106a) Thalictine (107) Thalmine (108)

CH3 H H CH3

CH3 H CH3 H

X)CH3 343

9.5.14. Type XlVa (5,6,7*4l\12-5\6,7,12*) The alkaloids of this type differ from the parent Type XIV alkaloids in that the former have oxygenation at C(5). (5,-) Alkaloids The two alkaloids of this group are methoxylated at C(6), C(7'), and C(8'); hydroxylated at C(5); and are imines at N(2'). The two alkaloids differ only in their substitution at C(12), with cultithalminine (12-demethylthalmiculimine)(285) being phenolic and thalmiculimine (382) being a methylether. Both bases have only been found as metabolites of Thalictrum cultratum (Ranunculaceae).


237

H3C

Alkaloid

E

Cultithalminine (285) Thalmiculimine (382)

H CH3

(5,5) Alkaloids The two alkaloids of this very small subgroup are methoxylated at C(5), C(12), and C(7'), differing only by being phenolic [5-Hydroxythalmine (6-demethylthalmiculine)(313)] or methoxylated [thalmiculine (383)] at C(6). Both bases are tertiary amines with N-methyl functions, and both alkaloids have only been isolated from Thalictrum cultratum (Ranunculaceae).

OH

H3C

Alkaloid 5-Hydroxythalmine (313) Thalmiculine (383)

H CH3

The four type XlVa alkaloids are restricted in their distribution to the genus Thalictrum, and quite specifically to T. cultratum.

238

P.L.Schiff,Jr.

9.5.15. Type XV (5\6,7,HM2-6,7\12+) The two alkaloids of this group, panurensine (110) and norpanurensine (2'norpanurensine)(109), are monophenolic at C(6), and are methoxylated at C(7), C(12), and C(6'). Each of the compounds possesses the R,R stereochemistry. The alkaloids are restricted in their distribution to A buta panurensis (Menispermaceae).

9.5.16. Type XVI (5\6,7,llM2-6\7,12*) This highly unusual alkaloid type features a novel C(5) to C(6') ether bridge that joins the monomeric halves of the molecule. The only alkaloid in this group is (J?,l?)-nemuarine (111), a base isolated from Nemuaron vieillardi (Monimiaceae).

TH3

111


239

9.5.17. Type XVII (5,6,7,8\10,12,13+-6,7\12+) All of the alkaloids of this group are unusual in that they bear 10,12,13- trioxygenation in Ring C of their molecule. Six of the seven alkaloids are 10-hydroxy, 12-methoxy compounds, while one is a 10,12-dimethoxy compound. In addition, all seven of the alkaloids have only been isolated from one plant, Thalictrum rochebrunianum (Ranunculaceae), and thus these compounds are of very restricted distribution. (£,-) Alkaloids There are two subgroups of these type of alkaloids. The alkaloids of the first subgroup, thalictrinine (220) and dihydrothalictrinine (198), are characterized by being benzyltetrahydroisoquinoline-benzylisoquinoline dimers. Thalictrinine (220) is characterized by having a carbonyl group at the ct'-carbon, while dihydrothalictrinine (198) is the reduced form and bears a p-hydroxy group at the a'-carbon.

220

240

P.L. Schlff, Jr.

The second small subgroup is represented by three alkaloids that are benzyhetrahydroisoquinoline-benzyldihydroisoquinoline dimers; thalibrunimine (112), Omethylthalibrunimine (210), and oxothalibrunimine (215). Oxothalibrunimine bears a carbonyl group at the a'-carbon, while O-methylthalibrunimine is methylated at C(10). OCH3

H3C

N3CH3 Alkaloid

E,

O-Methylthalibrunimine (210) Oxothalibrunimine (215) Thalibrunimine (112)

CH3 H H

E2JLS3 H O H

(5,5) Alkaloids Thalibrunine (113) and N'-northalibrunine (214) are the representatives of this small group. Both are bisbenzyltetrahydroisoquinolines and are phenolic at C(10). OCH3

H3C

Alkaloid

E

N'-Northalibrunine (214) Thalibrunine (113)

H CH3

The Bisbenzylisoquinoline Alkaloids - A Tabular Review 9.6.

241

One Diphenyl Ether Linkage (Head-to-Tail) and One Diphenyl Ether Linkage (Headto-Tail)

9.6.1. Type XX (6,7,8\12+-6,7,8\12*) These are head-to-tail linked bases that tend to occur most commonly in the several genera of the Menispermaceae. (-,/?) Alkaloids The two alkaloids that constitute this small subgroup are sciadoferine (217) and sciadoline (128). These alkaloids differ in the degree of oxidation of their A rings, in that the former is a 3,4-dihydroisoquinoline, while the latter is a true isoquinoline. These alkaloids are metabolites of Sciadotenia toxifera (Menispermaceae).

217

128

242

P.L.SchifT,Jr.

(R,R) Alkaloids Four of the five alkaloids within this small subgroup are cycleanine (121) derivatives, including cycleanine-N-oxide (232), N-desmethylcycleanine (233)(the N(2') desmethyl derivative of cycleanine), and (-)-norcycleanine (125), the last of which is really not a "nor" derivative, but is a C(7') Odemethylcycleanine. Cycleanine (121) has been isolated from various species of no less than ten genera, but with eight of the genera being from the family Menispermaceae, while the remaining two are from the Umbelliferae [an extremely unusual alkaloid-bearing family] and the Annonaceae. Cycleanine-N-oxide (232) has only been isolated from Synclisia scabrida (Menispermaceae)(as has cycleanine itself). N-Desmethylcycleanine (233) has only been found in Stephania glabra and Stephania pierrii (Menispermaceae), both plants having also served as a source of cycleanine. (-)-Norcycleanine (125) has been isolated from two plants, Isolona hexaloba (Annonaceae) and Stephania cepharantha (Menispermaceae), both of which have also served as a source of cycleanine (121). All of the alkaloids of this subgroup are methylated at N(2), and are C(6)/C(6') bismethoxylated. Phenolic compounds may result by substitution at C(7) and/or C(7'). ÔCH3

-R3 CH3O'

Alkaloid

Ei

£2

£3

Cycleanine (121) N-Desmethylcycleanine (233) Isochondodendrine (122) (-)-Norcycleanine (125)

CH3 CH3 H CH3

CH3 CH3 H H

CH3 H CH3 CH3

CH3cr 232

1 he fiisbenzyllsoquinoline Alkaloids - A Tabular Review

243

(S,S) Alkaloid The only naturally occurring alkaloid of this small group is (+)-norcycleanine (124)[which is really 7'-0-demethylcycleanine). This alkaloid is not as widely distributed as its R,R diastereoisomer (-)-norcycleanine (125). The (+)-isomer has only been isolated from two plants: Isolona hexaloba (Annonaceae) and Stephania cepharantha (Menispermaceae), neither of which are a source of the (-)-isomer (which was found in four Menispermaceous genera; Chondodendron, Cyclea, Epinetrum, and Synclisia. The base tetra-O-demethylcycleanine (128a) has been reported, but data was not available.

Alkaloid

R,

E2

R3

(+)-Norcycleanine (124) Tetra-O-Demethylcycleanine (128a)

CH3 H

CH3 H

CH3 H

(StR) Alkaloid The only alkaloid of this group is sciadenine (127) which is solely a metabolite of Sciadotenia toxifera (Menispermaceae). Sciadenine (127) has the same substitution as sciadoline (128) and sciadoferine (217)[two other alkaloids of the same plant], except that sciadenine contains a fully reduced ring A, while ring A of the other two alkaloids is oxidized to different degrees.

127

244

P.L. SchifT,Jr.

(?,?) Alkaloids There are two alkaloids of incompletely determined structure, protocuridine (126) and neoprotocuridine (123). In the case of the former, only the stereochemisty of the chiral carbon atoms at C(l) and C(l') is unknown, but in the case of the latter, the positions of the phenolic hydroxy groups and methoxy groups have not been settled with certainty, nor has the stereochemistry at C(l) and C(l'). Both of these alkaloids were isolated from curare.

123

9.6.2. Type XXI (6,7,8*41+,12-6,7\12*) (R,R) Alkaloids There are four alkaloids in the (-)-curinc family: (-)-curine (133), cycleacurine (134), 0,0-dimethylcurine (135), and 12'-Omethylcurine (140). These alkaloids differ in the position of various phenolic hydroxy groups and methoxy groups among the C(7), C(12), and C(6') positions. (-)-Curine (133) has been isolated from six genera of the Menispermaceae including Chondodendron, Cissampelos, Cyclea, Paracyclea, Pleogyne, and Stephania. In addition, this


245

alkaloid has been isolated from two Annonaceous plants Cleistopholis staudtii and Isolona hexaloba, as well as one plant of the Umbelliferae, Heracleum wallichi. Cycleacurine (134) has only been isolated from Cyclea peltata (Menispermaceae), while 0,0-dimethylcurine (135) is only a metabolite of Cylcea hypoglauca (Menispermaceae) and Guatteria megalophylla (Annonaceae). Finally, 12'-0-methylcurine (140) has only been isolated from Guatteria megalophylla (Annonaceae).

Alkaloid

R,

R2

R,

(-)-Curine (133) Cycleacurine (134) 0,0-Dimethylcurine (135) 12'-0-Methylcurine (140)

H H CH3 H

H H CH3 CH3

CH3 H CH3 CH3

There are two alkaloids of this series that bear a methylenedioxy group at C(6)/C(7) and are acetylated at N(2'). These are isocuricycleatjenine (410) and isocuricycleatjine (411), two compounds that differ only by the presence of a 7-methoxy group in the former and a 7-hydroxy group in the latter. These alkaloids have only been found in Cyclea atjehensis (Menispermaceae).

Alkaloid

R

Isocuricycleatjenine (410) CH3 Isocuricycleatjine (410) H Although distribution within the Menispermaceae is favored for this subgroup, these alkaloids are also found in the Annonaceae and Umbelliferae.

246

P.L.Schlff,Jr.

(S,S) Alkaloids The three alkaloids of this small subgroup differ only in their substitution (phenolic hydroxy or methoxy groups) at C(7) and C(12)/C(4"). Chondrofoline (131) has been isolated from Chondodendron platiphyllum (Menispermaceae) and two Annonaceous plants (Cleistopholis staudtii and Uvaria ovata), while the bisphenol (+)-curine (132) has been isolated from varying genera in three different plant families, including the Buxaceae, the Lauraceae, and the Menispermaceae. (+)-Curine (132) is a metabolite of several Menispermaceous species, including Abuta candicans, Chondodendron microphyllum, Cyclea barbata and Cyclea hainanensis. In addition, the alkaloid is found in several Buxus species (Fam Buxaceae) and Ocotea rodiei (Lauraceae). 4"-0-Methylcurine (139) has been isolated from two Menispermaceous species, Cissampelos pareira and Cyclea hainanensis. Although distribution into the Menispermaceae tends to predominate in this subgroup, these alkaloids are also found in other plant families.

Alkaloid

Ri

R2

Chondrofoline (131) (+)-Curine (132) 4"-0-Methylcurine (139)

CH3 H H

H H CH3

(R,S) Alkaloids The two nonquaternary alkaloids of this small subgroup are chondocurine (130) and norNb-chondocurine (230), the latter being the N(2') nor- derivative of the former. Chondocurine (also called chondrocurine) has been isolated from Chondodendron tomentosum and 2 species of Cyclea, all three plants being of the family Menispermaceae. The nor-base 230 and chondocurine have both been isolated from what is only described as Peruvian curare.


247

Alkaloid

R

Chondocurine (130) Nor-Nb-Chondrocurine (230)

CH3 H

The two quaternary alkaloids in this small subgroup are the bisquaternary chondocurarine (129) and monoquaternary (+)-tubocurarine (142). The structures of these two compounds are identical, save for the lesser degree of quaternization in the latter. Chondocurarine has only been isolated from Chondodendron tomentosum (Menispermaceae), while (+)-tubocurarine has been isolated from the same plant, as well as from Anomospermum grandifolium (Menispermaceae) and Peruvian curare.

Alkaloid

R

Chondocurarine (129) (+)-Tubocurarine (142)

CH3 H

The alkaloids of this small subgroup seem to be solely distributed within Menispermaceaous plants, particularly of the genus Chondodendron.

248

P.L.Schifr,Jr.

(S,R) Alkaloids Two closely related alkaloids from this group are curicycleatjenine (400) and curicycleatjine (401), compounds that contain a methylenedioxy function at C(5)/C(6). These two alkaloids differ only in the nature of the C(12) function, whereas in the former it is methoxy group and in the latter a hydroxy group. These alkaloids have only been isolated from Cyclea atjehensis (Menispermaceae). Hayatidine (136), an alkaloid of Cissampelos pareira (Menispermaceae), is a diastereoisomer of 12'-0-methylcurine (140). (-)-Tubocurarine (143), a diastereoisomer of (+)tubocurarine (142), has only been isolated from Chondodendron tomentosum (Menispermaceae).

Alkaloid

R

Curicycleatjenine (400) Curicycleatjine (401)

CH3 H

136


249

143

Racemic Alkaloid (+/-)-Curine dimethiodide has been isolated from extracts of Cissampelos pareira (Menispermaceae).

Partially characterized alkaloids Hayatine (137) and hayatinine (12-methylhayatine)(138) are alkaloids that have both been isolated from Cissampelos pareira (Menispermaceae), with the latter alkaloid also having been found in Cyclea hainanensis (Menispermaceae). The chirality of the C( 1) and C( 1') carbon atoms in these alkaloids has not been determined, although the two compounds are identical in molecular structure to (-)-curine (133) and 12'-Omethylcurine (140), respectively. The compound reported as (-)-tubocurine (144)(thought to be enantiomeric with chondrocurine [(+)tubocurine]) was not isolated in a pure form, and hence the physical properties were not determined [1].

137

250

P.L.Schiff,Jr.

144

9.7.

Two Diphenyl Ether Linkages (Head-to-Head) and One Diphenyl Linkage (Tail-toTail)

9.7.1. Type XVIII |6,7\8\12-6\7\12(11-11)) The alkaloids of this group are dibenzodioxin compounds in the top portion of the dimeric system, but biphenyls (not biphenyl ethers) in the lower portion of the rings. (5,-) Alkaloid The only alkaloid of this group is secolucidine (393), which is a secobisbenzylisoquinoline that has only been found in Pseudoxandra sclerocarpa (Annonaceae). The precursor to this alkaloid could have been medelline (318) from Pseudoxandra aff. lucida (Annonaceae), found in another subgroup of this series.

393

251

The Bisbenzylisoquinoline Alkaloids - A Tabular Review (5,5) Alkaloids

The compounds in this subgroup differ among each other in the following two manners: first, the degree of N-methylation, with three of the alkaloids being monosecondary amines, and one a bis-secondary amine; second, the placement of methoxy and phenolic hydroxy groups at C(12) and C(12') positions. Four of the six alkaloids are C(12) methoxy/C(12') hydroxy compounds, while the other two are C(12) hydroxy/C(12') methoxy compounds. Tiliacorinine (119), an alkaloid of this group, is a diastereoisomer of tiliacorine (118) and medelline (318). Nortiliacorinine A (116) has been isolated from four species of the genus Tiliacora, including T. racemosa, while nortiliacorinine B (117) has only been isolated from T. racemosa. The bissecondary amine pachyovatamine (250) has only been isolated from Pachygone ovata (Menispermaceae). Tiliacorinine (119) has been isolated from three species of Tiliacora^ including T. triandra, while tiliacorinine-2'-N-oxide (254) has only been isolated from T. triandra. Tiliarine (185) is solely a metabolite of T. racemosa, while yanangcorinine (388) has only been found in T. triandra. It can be observed that with the exception of pachyovatamine (250), all of the other five alkaloids have been isolated from Tilacora species. The S,S alkaloids appear to be of restricted distribution to the family Menispermaceae.

ÔCH3

V

"R4

Alkaloid

B,

&

&

&

Nortiliacorinine A (116) Nortiliacorinine B (117) Pachyovatamine (250) Tiliacorinine (119) Tiliarine (185) Yanangcorinine (388)

H CH, H CH, CH, CH,

CH3 CH, CH, CH, H H

H H H H CH, CH,

CH, H H CH, H CH,

252

P.L. Schiff, Jr.

254 (R,S) Alkaloids The two alkaloids of this series are tiliacorine (118) and nortiliacorine A (115). These alkaloids are both monophenolic at C(12'), but the position of the secondary amine at N(2) or N(2') in the latter has not been determined. Tiliacorine has only been isolated from three species of the genus Tiliacora: T funifera, T racemosa, and T. triandra, while the nor-base 115 has been isolated from T. funifera and T triandra. Tiliacorine (118) is a diastereoisomer of tiliacorinine (119) and medelline (318). The alkaloids of this group are only found in the genus Tiliacora of the Family Menispermaceae.

Alkali

£.

&

Nortiliacorine A (115)

CH3 H or H CH3


253

(S,R) Alkaloid Medelline (318) is the only alkaloid in this group. This compound has been isolated from just Pseudoxandra aff. lucida (Annonaceae). Medelline is a diastereoisomer of tiliacorine (118) and tiliacorinine (119). „OCH3

v

OCH 3 318

Unknown stereochemistry Dinklacorine (114) is likely a diastereoisomer of yanangcorinine (388), the latter of which has been isolated from Tiliacora triandra, while dinklacorine (114) has been found in both Tiliacora dinklagei and Tiliacora triandra. />CH 3

CH 3 . species Dt-7 (Monimiaceae), as well as from Guatteria guianensis (Annonaceae). Apateline (187) has been isolated from two Menispermaceous plants, Albertisia laurifolia and A. papuana, as well as from the Annonaceous Guatteria guianensis. Apateline has only been isolated from one Daphnandra species, D. apatela (Monimiaceae). The occurrence of these alkaloids appears to be restricted to one genus each in the Annonaceae and the Monimiaceae, and two genera of the Menispermaceae.

263


Alkaloid

R,

R2

R,

Apateline (187) N-Methylapateline (207) N-Methylnorapateline (208) 2-N-Methyltelobine (418) Telobine (160)

H CH, CH, CH, H

H H H CH, CH,

CH, CH, H CH, CH,

(S,S) Alkaloids By far the largest subgroup of alkaloids within the Type XXIII bases is that subgroup in which the S,S stereochemistry exists at C(l)/C(l'). The thirteen alkaloids of this subgroup differ in their substitution at the N(2), C(12), C(6'), and N(2') positions. Six of the thirteen alkaloids are secondary amines at N-2, while five are secondary amines at N-2\ Two of the alkaloids, 2'norcocsoline (421) and 2'-norcocsuline (329), are bis secondary amines. Eight of the thirteen alkaloids are phenolic at C(12), but only two [12-O-methyltricordatine (419) and tricordatine (161) are phenolic at C(6')]. Isotrilobine (157) is the fully methylated parent alkaloid of the group. There are three N-oxide alkaloids within this group, including cocsuline-N-2-oxide (231), cocsoline-2'P-N-oxide (398), and 12-0-methylcocsoline-2'P-N-oxide (414). Cocsoline (152) and its analogs, O-methylcocsoline (239), 2'-norcocsoline (421), cocsoline-2'P-N-oxide (398), and 12O-methylcocsoline-2'p-N-oxide (414) have only been isolated from genera within the Menispermaceae, including Albertisia, Anisocycla, Cocculus, Pachygone, and Synclisia. Cocsuline (153)(N-methylcocsoline) has likewise only been isolated from Albertisia, Anisocycla, Cocculus, and Synclisia species, while 2'-norcocsuline (329) has been found in Albertisia and Pachygone species. Trilobine (163) has been isolated from Anisocycla, Cocculus, and Pachygone species, while isotrilobine (157) has been isolated from species of Albertisia, Anisocycla, Cocculus, Pachygone, and Stephania. Nortrilobine (247) has only been isolated from Pachygone ovata (Menispermaceae). Tricordatine (161) has been found in species of Cocculus, Pachygone, and Triclisia. In conclusion, all thirteen alkaloids of this subgroup have only been found in genera of the Menispermaceae. These genera include: Albertisia, Anisocycla, Cocculus, Pachygone, Stephania, and Synclisia. Only the occurrence of tricordatine (161) in Triclisia subcordata is from a different Menispermaceous genus.

264

P.L. Schiff, Jr.

Alkaloid

R,

R2

Cocsuline (153) Isotrilobine (157) 12-O-Methyltricordatine (419) Tricordatine (161)

H CH3 CH3 H

CH3 CH3 H H

Alkaloid

R

Cocsoline (152) O-Mcthylcocsolinc (239)

H CH3

AMo>d

E

12'-0-Demethyltrilobine (155) Trilobinc (163)

H CH3

265


W H'

Alkaloid

R

2'-Norcocsoline (421) Nortrilobine (247)

H CH,

H3C

231

W

H'

•«CH,

H'

ÔCH3 414

266

P.L.Schlff,Jr.

9.9.2. Type XXIIIa (6*,7Ml\12-5,6,7\8*,12*) The alkaloids of this group are the same as those in Type XXIII with regard to their ether linkages, but differ by the presence of C(5') oxygenation in the form of a phenolic hydroxy group. (-,5) Alkaloids The four alkaloids of this group have only been found as metabolites of Cocculus pendulus (Menispermaceae). These compounds are characterized by unsaturation in ring B, with 1,2-dehydrokohatamine (289) and 1,2-dehydrokohatine (290) being 3,4-dihydrobenzylisoquinoline derivatives, while siddiquamine (371) and siddiquine (372) are benzylisoquinoline derivatives. 1,2-Dehydrokohatamine (289) and 1,2-dehydrokohatine (290) differ in the nature of substitution at C(12), with the former being a methyl ether while the latter is phenolic. A similar analogy is true for siddiquamine (371) and siddiquine (372).

Alkaloid

R

1,2-Dehydrokohatamine (289) 1,2-Dehydrokohatine (290)

CH3 H

AlKalpid

E

Siddiquamine (371) CH3 Siddiquine (372) H


267

(R,S) Alkaloids The two alkaloids of this small subgroup, 5-hydroxyapateline (309) and 5-hydroxytelobine (310), have only been found as constituents of Cocculus pendulus (Menispermaceae). These two alkaloids differ in their substitution at C(12), with the former being phenolic and the latter a methyl ether. Neither apateline (187) nor telobine (160) have been isolated from the genus Cocculus, but apateline (187) has been found in several other Menispermaceous genera, while telobine (160) has been isolated from genera of the Monimiaceae and Annonaceae.

Alkaloid

R

5-Hydroxyapateline (309) 5-Hydroxytelobine (310)

H CH3

(5,5) Alkaloids The two alkaloids of this subgroup, kohatamine (314) and kohatine (236) are the ring B fully reduced parent alkaloids of 1,2-dehydrokohatamine (289) and 1,2-dehydrokohatine (290), as described above. As with their oxidized counterparts, kohatamine (314) and kohatine (236) have only been isolated from one plant, Cocculus pendulus (Menispermaceae).

Alkaloid

E

Kohatamine (314) Kohatine (236)

CH3 H

268

P.L.Schifr,Jr.

9.9.3. Type XXIV - (6,r,8+,ll\12-6,7%8#,12#) The alkaloids of this group are characterized by two diphenyl ether bridges linking the dimer in a head-to-head fashion and one diphenyl ether bridge linking the dimer in a tail-to-tail manner. The head-to-head linkages are unusual in that they bond C-7 to C-8' and C-8 to C-7\ thereby producing a molecule with a very different spatial configuration than that found in the more traditional Type XXIII alkaloids (C-6 to C-7' and C-7 to C-8'). All of the alkaloids of Type XXIV share one structural feature - the presence of a C(6) methoxy group. (£,-) Alkaloids

Menisarine (165), a ring B' 3,4-dihydrobenzylisoquinoline alkaloid found in Cocculus leaebe and C. sarmentosus (Menispermaceae), is the only representative of this small subgroup whose structure has been firmly established. The structure of normenisarine has not been fully elucidated, but it is known that it is a derivative of menisarine, in which there is one phenolic group at one of the three ring substituted positions [C(6) or C(12) or C(6')]. As before, the prefix "nor-" is used incorrectly, and one would erroneously assume that normenisarine was in fact N-demethylmenisarine. Normenisarine has only been isolated from Cocculus thlobus (Menispermaceae). The two representatives of this small subgroup appear to be confined to a single genus (Cocculus) of the Menispermaceae.

165

(S,S) Alkaloids

The least substituted alkaloid of this subgroup is cocsilinine (397), which is a bissecondary amine that is also biphenolic at C(12) and C(6'). The other five alkaloids of this subgroup are derivatives of cocsilinine (397), in which varying numbers of methyl groups are found on the nitrogen atoms and the phenolic carbon atoms at C(12) and C(6'). The structure of cocsiline (396) has not been fully elucidated because the position of the single N-methyl group at either N(2) or N(2') has not been firmly established. Monosecondary amines in this subgroup include N-norcocsulinine (422)(N-2 nor-), and gilletine (202) (N-2r nor-). Five of the six alkaloids are phenolic at C(12) [the exception being gilletine (202)], while four of the six alkaloids are phenolic at C(6') [exceptions being O-methylcocsulinine (415) and cocsiline (396)].


269

With the exception of gilletine (202), the other five alkaloids, including cocsilinine (397), cocsiline (396), cocsulinine (164), N-norcocsulinine (422), and O-methylcocsulinine (415) have only been isolated from one plant, Cocculus pendulus (Menispermaceae). Gilletine (202) has been found as a metabolite of Triclisia gilletti (Menispermaceae).

„OCH3

'H

Alkaloid

R.

Cocsiline (396)

H

Cocsilinine (397) Cocsulinine (164) Gilletine (202) O-Methylcocsulinine (415) N-Norcocsulinine (422)

CH, H CH, CH, CH, H

R2 or H H H CH, H H

R3 CH,

CH,

CH, H H H CH, H

H H CH, H CH, CH,

It can be concluded that the occurrence of the alkaloids of this subgroup is almost completely restricted to one plant, Cocculus pendulus (Menispermaceae). Only one other Menispermaceous species, Triclisia gilletti, is known to contain an alkaloid of this type. Hence, the distribution of these bases is, for the time being, restricted to the Family Menispermaceae. 9.9.4. Type XXVIII ( 6 , 7 \ r f l l \ 1 2 - 6 \ 7 \ 1 2 i ) Angchibangkine (394), the sole member of this group of alkaloids, has only been found as a metabolite of Pachygone dasycarpa (Menispermaceae). This alkaloid is the prototype of a new group, in which the dibenzo-p-dioxin link in the top portion of the molecule is linked differently (C-7 to C-6' + C-8 to C-7') than in those more commonly occurring alkaloids of Group XXIII (C-6 to C-7' + C-7 to C-8'). The alkaloid possess the S,S stereochemistry at its chiral centers.

270

P.L. Schiff, Jr.

394 Incompletely characterized alkaloids Isogilletine-N-oxide (204), an alkaloid of Triclisia gilletti (Menispermaceae), is a compound of undefined stereochemistry. The molecular structure of isogilletine-N-oxide (204) is identical to that of gilletine (202), but with the addition of the oxide to the N(2) position. Pendilinine (425)[which may also be designated 6'-0-methylgilletine (425)], an alkaloid of Cocculuspendulus (Menispermaceae), is also an alkaloid of unestablished stereochemistry. The placement of these alkaloids in this subgroup is consistent with their plant sources being Menispermaceous plants of the genera Cocculus and Triclisia.

425

The Bisbenzylisoquinoline Alkaloids - A Tabular Review 9.10.

271

One Diphenyl Ether and One Benzylphenyl Ether Linkage (Head-to-Head) and One Diphenyl Ether Linkage (Tail-to-Tail)

9.10.1. Type XXV - (6,7,8\HM2,13-6,7\12*[8-6j) This very unique and quite small group of alkaloids is characterized by a head-to-head linkage that is accomplished by both a diphenyl ether and a benzylphenyl ether, with the tail-totail linkage being the more classical diphenyl ether. In addition, the C(8) position is unusual in that it is the ring A terminus for both the diphenyl ether link and the benzylphenyl ether link. This type of linkage is accompanied by the presence of a carbonyl group at C(7), thus altering the customary aromaticity of ring A. The parent alkaloid of the group is repanduline (168), a base that has only been isolated from three species of the genus Daphnandra; D. dielsii, D. repandula, and D. tenuipes. The other alkaloid of the group, pseudorepanduline (167), differs from repanduline in that the former has a methoxy group at C(12) and a hydroxy group at C(13),while the latter has a methylenedioxy group at those positions. Pseudorepanduline (167) has only been found in Daphnandra dielsii and an unnamed Daphnandra species. The chirality at C(l) and C(l') has not been established for these alkaloids.

272

P.L.Schifr,Jr.

9.11. One Diphenyl Ether and One Benzylphenyl Ether Linkage (Head-to-Tail) and One Diphenyl Ether Linkage (Head-to-Tail) 9.11.1. Type XXVI - (6,7,8\l2*-6,7,8*,12*lll-7)) There are only four alkaloids in this small group, with their distribution being restricted to only four genera of the family Menispermaceae. These alkaloids are characterized by head-to-tail linkages, with two diphenyl ether linkages and one benzylphenyl ether linkage. Each of the four alkaloids is characterized by R9R stereochemistry at the chiral C(l) and C(l') carbon atoms. There are two parent alkaloids for this subgroup; insulanoline (169) and insularine (7methylinsulanoline)(170). Insulanoline has been isolated from three Cyclea species (C. hypoglauca, C insularis, C sutchuenensis)(Memspcrmaceae), while insularine has been isolated from Cissampelos pareira, the same three Cyclea species that insulanoline has been isolated from, and from Paracyclea ochiaiana, Stephania japonica, and Stephania japonica var. australis (Menispermaceae). The other two alkaloids of this group are oxides of insularine, insuarine-2pN-oxide (408) and insularine-2'P-N-oxide (409), with both compounds only being reported as metabolites of Cyclea sutchuenensis (Menispermaceae). It appears that the alkaloids of this group have a very restricted distribution to several selected genera of the Menispermaceae.

Alkaloid

R

Insulanoline (169) Insularine (170)

H CH3

408


273

409 Acknowledgements. The author would like to acknowledge the patience and assistance of many individuals who performed multiple duties, including filing, photocopying, and obtaining manuscripts from various libraries: Ms. Mary Birr, Ms. Beth Kitchen, Ms. Geraldine Robinson, Ms. Cathy Stevenson, Mr. Tawfeq Al-Howiriny, Dr. Adnan Al-Rehaily, and Dr. Maged Sharaf. A special debt of thanks goes to Dr. Al-Rehaily, who was so kind as to produce the structures. The efforts of Ms. Ruth Quimby and NAPRALERT (Program for Collaborative Research in the Pharmaceutical Sciences, College of Pharmacy, The University of Illinois at Chicago) are deeply appreciated.

REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23.

KP Guha, B Mukherjee, and R. Mukherjee, J. Nat. Prod. 42, 1 (1979). PL SchifT, Jr., J. Nat. Prod. 46, 1 (1983). PL SchifT, Jr., J. Nat. Prod. 50, 529 (1987). PL SchifT, Jr., J. Nat. Prod. 54, 645 (1991). PL SchifT, Jr., J. Nat. Prod. 60, 934 (1997). M-C Chalandre, H Guinaudeau, and J Bruneton, C.R. Acad. Sci., Ser. 2, 301, 1185 (1985). H Guinaudeau, M Bohlke. L-Z Lin, CK Angcrhofer, GA Cordell, J. Nat. Prod. 60, 258 (1997). D Cortes, J Saez, R Hocquemiller, A Cave\ and A Cave\ J. Nat. Prod. 48, 76 (1985). Z Xue, Y Wu, P Zhang, J Ma, and J He, Acta Botantca Sinica, 27, 630 (1985); Chem. Abstr. 104, 106299 (1986). M Lavault, J Bruneton, A Cave, KC Chan, JR Deverre, T Sevenet, and H Guinaudeau, Can. J. Chem. 65, 343 (1987). IRC Bick and S Sotheeswaran, Aust. J. Chem. 31, 2077 (1978). S Berthou, M LeboeuT, A Cave\ and H Guinaudeau, J. Nat. Prod. 52, 95 (1989). M Leboeuf, M-L Abouchacra, A Cavc\ and M.Debray, Plant. Med. Phytother. 21, 106 (1987). D Kostalova, D Uhrin, V Hrochova, and J Tomko, Collect. Czech. Chem. Commun., 52, 242 (1987). JM Saa, MV Lakshmikantham, MJ Mitchell, and MP Cava, J. Org. Chem. 41, 317 (1976). M LeboeuT, M-L Abouchacra, T Sevenet, and A Cave\ Plant. Med. Phytother. 16,280 (1982); Chem. Abstr. 100, 20463 (1984). Atta-ur-Rahman and AA Ansari, J. Chem. Soc., Perkin I 5, 283 (1983); Chem. Abstr. 101, 3974 (1984). J-F Weber, A-M LeRay, J Bruneton, and A Foumet, J. Nat. Prod. 52, 81 (1989). SA Ross, T Gozler, A J Freyer, M Shamma, and B Cubukcu, J. Nat. Prod. 49, 159 (1986). V Hrochova and D Kostalova, Cesk. Farm. 36, 457 (1987); Chem. Abstr. 108, 128549 (1988). A Karimov and R Shakirov, Chem. Nat. Compounds 29, 335 (1993). R Verpoorte, AHM van Rijzen, J Siwon, and AB Svendsen, Planta Med. 34, 274 (1978). BK Cassels, E Breitmaier, and MH Zenk, Phytochemistry 26, 1005 (1987).

274

24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. 64. 65. 66. 67. 68. 69. 70.

P.L.SchifT,Jr. I Khamidov, M Faskhutdinov, MV Telezhcnetskaya, A Karimov, MG Levkovich, ND Abdullaev, and R Sh Shakirov, Chem. Nat. Cpds., 32, 59 (1996). A-U Rahman and H Ahmad, Phytochcmistry 31, 1835 (1992). IRC Bick and TG Whalley, Univ. Queensland Papers. Dept. Chem. 1, 7 (1948); Chem. Abstr. 43, 6787 (1949). IRC Bick, WI Taylor, and AR Todd, J. Chem. Soc. 1953, 695 (1953). IRC Bick, H-M Leung, and Ml Richards, Aust. J. Chem. 33, 225 (1980). D Kostalova, V Hrochova, and J Tomko, Chem. Pap. 40, 389 (1986); Chem. Abstr. 105, 112071 (1986). Y Sugimoto, Y Sugimura, and Y Yamada, Phytochcmistry 27, 1379 (1988). Y Sugimoto, Y Yamada, and Y Sugimura, J. Nat. Prod. 52, 199 (1989). N Kashiwaba, S Morooka, M Kim lira, Y Murakoshi, J Toda, and T Sano, Chem. Pharm. Bull. 42, 2452 (1994). Y Sugimoto, Y Yamada, and Y Sugimura, Jpn. Kokai Tokkyo Koho JP 03 34,980 [91 34,980] (1991); Chem. Abstr. 114, 254000 (1991). B Tantisewie, S Amurrio, H Guinaudeau, and M Shamma, J. Nat. Prod. 52, 846 (1989). WHMW Herath, SF Hussain, AJ Freyer, H Guinaudeau, and M Shamma, J. Nat. Prod. 50, 721 (1987). Z Wu, D Guoping, T Wu, and Z Min, Zhiwu Xuebao 32, 210 (1990); Chem. Abstr. 113, 168973 (1990). W-N Wu, JL Beal, R-P Leu, and RW Doskotch, Lloydia 39, 378 (1976). H Guinaudeau, AJ Freyer, M Shamma, and KHC Baser, Tetrahedron 40, 1975 (1984). W-N Wu, JL Beal, and RW Doskotch, J. Nat. Prod. 43, 143 (1980). E Fujita, T Tomimatsu, and Y Kano, Yakugaku Zasshi 82, 311 (1962); Chem. Abstr. 58, 3468 (1963). E Fujita, T Tomimatsu, and Y Kitamura, Bull. Inst. Chem. Res. 42, 235 (1964); Chem. Abstr. 62, 5310 (1964). D Dwuma-Badu, JSK Ayim, AN Tackie, JE Knapp, DJ Slatkin, and PL Schiff, Jr., Phytochcmistry 14, 2524 (1975). SM Kupchan, AJ Lipea, RL Baxter, and HPH Hintz, J. Org. Chem. 38, 1846 (1973). IRC Bick and GK Douglas, Chem. and Ind. 1965, 694 (1965). P Dute, M-C Chalandre, P Cabalion, and J Bruneton, Phytochemistry 27, 655 (1988). M Shamma, JE Foy, and GA Miana, J. Am. Chem. Soc. 96, 7809 (1974). GA Miana, JE Foy, RD Minard, and M Shamma, Experientia 35, 1137 (1979). MR Falco, JX Devries, Z Maccio, and IRC Bick, J. Chem. Soc. D 1971, 1056 (1971). J Siwon, R Verpoorte, T VanBcck, H Meerburg, and AB Svendsen, Phytochemistry 20, 323 (1981). TA van Beek, R Verpoorte, and AB Svendsen, J. Org. Chem. 47. 898 (1982). IRC Bick, PS Clezy, and WD Crow, Aust. J. Chem. 9, 111 (1956). Z Ma, Q Wang, and M Liu, Zhongcaoyao 23, 539 (1992); Chem. Abstr. 118, 87479 (1993). M Tomita and T Kugo, J. Pharm. Soc. Japan 75, 753 (1955); Chem. Abstr. 49, 13597 (1955). R Chatterjee, J. Ind. Chem. Soc. 28, 225 (1951). M Tomita and T Abe, J. Pharm. Soc. Japan 72, 773 (1952). H. Pommerehne, Arch. Pharm. 233, 127 (1895). R Chatterjee, A Banerjee, AK Barua, and AK Dasgupta, J. Ind. Chem. Soc. 31, 83 (1954). SF Hussain, MT Siddiqui, L Khan, AJ Freyer, H Guinaudeau, and M Shamma, J. Nat. Prod. 49, 538 (1986). R Torres, F Delle Manache, and GB Marini-Bettolo, Planta Med. 37, 32 (1979). A Karimov, MF Faskhutdinov, ND Abdullaev, MG Levkovich, EG Mil'grom, YaV Rashkes, and R Shakirov, Chem. Nat. Compounds 29, 774 (1993). AP Orekhov, Arch. Pharm. 271, 323 (1933). A Karimov and R Shakirov, Chem. Nat. Compounds 29, 69 (1993). D Kostalova, B Brazdovicova, and J Tomka, Chem. Zvesti 30, 226 (1976). TH Yang and S Lu, Yakugaku Zasshi 80, 847 (1960); Chem. Abstr. 54, 23187 (1960). R Chatterjee and A Banerjee, J. Ind. Chem. Soc. 30, 705 (1953). GA Miana, M Ikram, and SA Warsi, Pak. J. Sci. Ind. Res. 12, 159 (1969); Chem. Abstr. 72, 55716 (1970). MN Ali and AA Khan, Pak. J. For. 28, 25 (1978); Chem. Abstr. 90, 43706 (1979). JE Lect, SF Hussain, FD Minard, and M Shamma, Heterocycles 19, 2355 (1982). TH Yang and S Lu, Yakugaku Zasshi 80, 849 (1960); Chem. Abstr. 54, 23188 (1960). A Karimov and KL Lutfiillin, Khim. Prir. Soedin. (2), 249 (1986); Chem. Abstr. 105, 197034 (1986).

The Misbenzylisoquinoline Alkaloids - A Tabular Review 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 95. 96. 97. 98. 99. 100. 101. 102. 103. 104. 105. 106. 107. 108. 109. 110. HI. 112. 113. 114. 115.

275

GA Miana and M Ikram, Pak. J. Sci. Ind. Res. 13, 49 (1970); Chem. Abstr. 73, 117192 (1970). G-S Liu, B-Z Chen, W-Z Song, and P-G Xiao, Chih Wu Hsueh Pao 20, 255 (1978); Chem. Abstr. 90, 12202 (1979). G-H Zhou and C-L Liu, Chung Ts'ao Yao 11, 490 (1980); Chem. Abstr. 94, 214459 (1981). M Lavault, A Fournet, H Guinaudeau, and J Bruneton, Chem. Pharm. Bull. 34, 1148 (1986). A Karimov, MG Levkovich, ND Abdullaev, and R Shakirov, Chem. Nat. Compounds 29, 361 (1993). R Stadler, S Loeffler, BK Cassels, and MH Zenk, Phytochemistry 27, 2557 (1988). GA Greathouse and NE Rigler, Plant Physiol. 15, 563 (1940). SF Hussain, L Khan, KK Sadozai, and M Shamma, J. Nat. Prod. 44, 274 (1981). M Tomita and TH Yang, Yakugaku Zasshi 80, 845 (1960); Chem. Abstr. 54, 23187 (I960). B Brazdovicova, D Kostalova, J Tomko, and HY Jin, Chem. Zvesti 34, 259 (1980). R Chatterjee, MP Guha, and AK Dasgupta, J. Ind. Chem. Soc. 29, 921 (1952). C-X Liu, P-G Xial, and GS Liu, Phytotherapy Res. 5, 228 (1991). T Goina, P Petcu, and M Pitea, Rom. Pat. 63,426; Chem. Abstr. 90, 76555 (1979). MM Yusupov, A Karimov, and KL Lutfullin, Chem. Nat. Compounds 26, 105 (1990). J Slavfk and L Slavfkova, Collect. Czech. Chem. Commun., 60, 1034 (1995). I Khamidov, MV Telezhenetskaya, A Karimov, and R Shakirov, Chem. Nat. Cpds., 31, 417 (1995). V Hrochova and D Kostalova, Cesk. Farm. 34, 412 (1985); Chem. Abstr. 104, 106264 (1986). M Ikram and F Khan, Planta Med. 32, 212 (1977). T Yupraphat, P Pachaly, and F Zymalkowski, Planta Med. 25, 315 (1974). H Guinaudeau, L-Z Lin, N Ruangrungsi, and GA Cordcll, GA. J. Nat. Prod. 56, 1989 (1993). L Kostalova, V Hrochova, D Uhrin, and J Tomko, Chem. Pap. 42, 841 (1988); Chem. Abstr. 110, 170219 (1989). A Cave\ M Leboeuf, R Hocquemiller, A Boquet, and A Fournet, Planta Med. 35, 31 (1979). PP Panov, NM Mollov, and LN Panova, Dokl. Bolg. Akad. Nauk 24, 675 (1971); Chem. Abstr. 75, 148465 (1971). J Slavik, J Bochorakova, D Kostalova, and V Hrochova, Chem. Pap. 39, 537 (1985). KS Khusainova and YD Sadykov, lzv. Akad. Nauk Tadzh. SSR, Otd. Fiz.-Mat., Khim. Geol. Nauk (I), 41 (1986); Chem. Abstr. 105. 130695 (1986). R Chatterjee and MP Guha, J. Am. Pharm. Assoc. 39, 181 (1950). TH Yang, Yakugaku Zasshi 80, 1304 (I960); Chem. Abstr. 55, 3005 (1961). G Aguilar-Santos and S Villareal, Proc. Symp. Phytochem. Univ. Hongkong 1961,48 (1961); Chem. Abstr. 61, 16442(1964). AA Sioumis and VN Vashist, Aust. J. Chem. 25, 2251 (1972). FV Bruchhausen, GA Santos, and C Schafer, Arch. Pharm. 293, 454 (1960). JC Regalado, Jr., C-y Gao, E Fu, F-t Lin, M-c Lin, LK Wong, and PL SchifT, Jr., Heterocycles 26, 2573 (1987). M Tomita, T Sawada, M Kozuka, M Takeuchi, and M Akasu, Yakugaku Zasshi 89, 1678 (1969). J Kunitomo, M Oshikata, and M Akasu, Yakugaku Zasshi 101,951 (1981); Chem. Abstr. 96, 31640 (1982). K Kinoshita, K Morikawa, M Fujita, and S Natori, Planta Med. 58, 137 (1992). J-Z Deng, S-X Zhao, and Z-C Miao, Phytochemistry 31, 1448 (1992). M Tomita and H Kishikita, J. Pharm. Soc. Japan 64, 240 (1944); Chem. Abstr. 45, 5173 (1951). Y Feng and H Chen, Yaowu Fenxi Zazhi 5, 28 (1985); Chem. Abstr. 102, 172482 (1985). NM Mollov, V St Georgiev, PP Panov, and D Jordanov, C.R. Acad. Bulg. Sci. 20, 333 (1967). BK Wali, V Paul, and KL Handa, Ind. J. Pharm. 26, 69 (1964). MM Yusupov, A Karimov, R Shakirov, PG Gorovoi, MF Faskhutdinov, MG Levkovich, and ND Abudllaev, N.D., Chem. Nat. Compounds 29, 338 (1993). MM Yusupov, A Karimov, MG Levkovich, ND Abdullaev, and R Shakirov, Chem. Nat. Compounds 29, 43 (1993). A Karimov, ND Abdullaev, and R Shakirov, Chem. Nat. Compounds 29, 219 (1993). A Karimov, AB Butayarov, MM Yusupov, RT Mirzamatov, and R Shakirov, Chem. Nat. Compounds 29, 523 (1993). A Karimov, MV Telezhenetskaya,KL Luftrullin, and SYu Yunusov, Khim. Prior. Soedin 1976, 558 (1976). AM Karimov, MV Telezhenetskaya,KL Luttullin, and SYu Yunusov, Khim. Prir. Soedin., 1977, 80 (1977).

276

P.L.Schiff,Jr.

116. 117. 118. 119. 120. 121. 122. 123. 124. 125. 126. 127. 128. 129. 130.

A Karimov, MG Lcvkovich, ND Abdullaev, and R Shakirov, Chem. Nat. Compounds 29, 63 (1993). D Cortes, R Hocquemiller, A Cave, and J Saez, J. Nat. Prod. 49, 854 (1986). JW Loder and RH Nearn, Aust. J. Chem. 25, 2193 (1972). S Berthou, A Jossang, H Guinaudeau, M Leboeuf, and A Cav6, Tetrahedron 44, 2193 (1988). M-L Abouchacra, M Leboeuf, H Guinaudeau, and A Cave., J.Nat. Prod. 50, 375 (1987). V Fajardo, M Garrido, and BK Cassels, Heterocycles 15, 1137 (1981). V Fajardo, A Urzua, and BK Cassels, Heterocycles 12, 1559 (1979). J Leet, V Fajardo, A J Freyer, and M Shamma, J. Nat. Prod. 46, 908 (1983). R Torres, L Villarroel, A Urzua, and V Fajardo, Fitoterapia 63, 376 (1992). JE Leet, AJ Freyer, RD Minard, M Shamma, and V Fajardo, J. Chem. Soc., Perkin Trans. I, 651 (1984). JE Leet, AJ Freyer, RD Minard, and M Shamma, J. Chem. Soc., Perkin Trans. I, 1565 (1985). M Lavault, A Fournet, H Guinaudeau, and J Bruneton, J. Chem. Res. (S), 248 (1985). M Lavault, A Fournet, H Guinaudeau, and J Bruneton, J. Chem. Res. (M), 2786 (1985). H Guinaudeau, AJ Freyer, and M Shamma, Natural Product Reports, 477 (1986). S Peng, L Chen, G Zhang, W Pan, and W Chen, Tianran Chanwu Yanjiu Yu Kaifa 2, 37 (1990); Chem. Abstr. 115,314624(1991). H Kondo, M Tomita, and S Uyeo, Chem. Ber. 70B, 1890 (1937). Z Chen, S Yang, and X Ding, Nanjing Yixueyuan Xuebao 5,203 (1985); Chem. Abstr. 104, 106271 (1986). Y Chen, Y Pan, and S Fang, Zhongcaoyao 18, 438 (1987); Chem. Abstr. 108, 19257 (1988). U Prawat, P Wiriyachitra, V Lojanapiwatna, and S Nimgirawath, J. Sci. Soc. Thailand 8,65 (1982); Chem. Abstr. 97, 107084 (1982). K Likhitwitayawuid, CK Angerhofer, GA Cordell, JM Pezzuto, and N Ruangrungsi, J. Nat. Prod. 56, 30 (1993). M Zhi-Da, L Ge, X Guang-Xi, M Iinuma, T Tanaka, and M Mizuno, Phytochemistry 24, 3084 (1985). A Patra, AJ Freyer, H Guinaudeau, M Shamma, B Tantisewie, and K Pharadai, J. Nat. Prod. 49,424 (1986). JE Leet, V Elango, SF Hussain, and M Shamma, Heterocycles 20, 425 (1983). SF Hussain, L Khan, H Guinaudeau, JE Leet, AJ Freyer, and M Shamma, Tetrahedron 40, 2513 (1984). JD Dutcher, J. Am. Chem. Soc. 74, 2221 (1952). IRC Bick and PS Clezy, J. Chem. Soc. 1960, 2402 (1960). JD Dutcher, J. Am. Chem. Soc. 68, 419 (1946). K Dahem, P Pachaly, and F Zymalkowski, Arch. Pharm. 310, 95 (1977). JR Boissier, G Combes, R Pemet, and C Dumont, Lloydia 28, 191 (1965). J Lemli, C GalefFi, 1 Messana, M Nicoletti, and GB Marini-Bettolo, Planta Med. 51, 68 (1985). H King, J. Chem. Soc. 1940, 737 (1940). PG Waterman and I Mohammed, Planta Med. 50, 282 (1984). K Panichpol, RD Waigh, and PG Watermann, Phytochemistry 16, 621 (1977). SM Kupchan, AC Patel, and E Fujita, J. Pharm. Sci. 54, 580 (1965). DL Galinis, DF Wiemer, and J Cazin, Jr., Tetrahedron 49, 1337 (1993). B Kanyinda, R Vanhaelen-Fastre, and M Vanhaelen, J. Nat. Prod. 56, 618 (1993). K Ito, H Furukawa, K Sato, and J Takahashi, Yakugaku Zasshi 89, 1163 (1969). S Jain, K Shukla, and DS Bhakuni, Fitoterapia 62, 391 (1991). B Kanyinda, B Diallo, R Vanhaelen-Fastre, and M Vanhaelen, Planta Med. 55, 394 (1989). M Ikram, N Shaft, and M Abu Zarga, Planta Med. 45, 253 (1982). DS Bhakuni and PP Joshi, Tetrahedron 31, 2575 (1975). FC Ohiri, R Verpoorte, and AB Svendsen, Planta Med. 42, 142 (1981). FC Ohiri, R Verpoorte, AB Svendsen, Planta Med. 47, 87 (1983). B Kanyinda, R Vanhaelen-Fastre, M Vanhaelen, and R Ottinger, J. Nat. Prod. 56, 957 (1993). Ml Khan, M Ikram, and SF Hussain, Planta Med. 47, 191 (1983). S Al-Khalil, D Al-Eisawi, M Sharaf, and PL Scruff, Jr., Planta Med 59, 276 (1993). FV Bruchhausen, AC Santos, J Knabe, and GA Santos, Arch. Pharm. 290, 232 (1957). TA van Beek, R Verpoorte, AB Svendsen, AC Santos, and LP Olay, J. Nat. Prod. 46, 226 (1983). BMR Bandara, NK Ulangasekara, ULB Jaya-singhe, V Karunaratne, GP Wannigama, M Bokel, W Kraus, and S Sotheeswaran, Planta Med. 56, 245 (1990). E Schlittler and N Weber, Helv. Chem. Acta 55, 2061 (1972).

131. 132. 133. 134. 135. 136. 137. 138. 139. 140. 141. 142. 143. 144. 145. 146. 147. 148. 149. 150. 151. 152. 153. 154. 155. 156. 157. 158. 159. 160. 161. 162. 163. 164. 165.

The Bisbenzylisoquinoiine Alkaloids - A Tabular Review 166. 167. 168. 169. 170. 171. 172. 173. 174. 175. 176. 177. 178. 179. 180. 181. 182. 183. 184. 185. 186. 187. 188. 189. 190. 191. 192. 193. 194. 195. 196. 197. 198. 199. 200. 201. 202. 203. 204. 205. 206. 207. 208. 209.

277

DS Bhakuni, NC Gupta, and MM Dhar, Expcrientia 26, 241 (1970). AI Spiff, V Zabel, WH Watson, MA Zemaitis, AM Ateya, DJ Slakin, JE Knapp, and PL Schiff, Jr, J. Nat. Prod. 44, 160(1981). AN Tackie, D Dwuma-Badu, T Okarter, JE Knapp, DJ Slatkin, and PL Schiff, Jr., Lloydia 37, 1 (1974). AN Tackie, D Dwuma-Badu, TU Okarter, JE Knapp, DJ Slatkin, and PL Schiff, Jr., Phytochemistry 12, 2509 (1973). R Huls and C Detry, Bull. Soc. Roy. Sci. Liege 42, 73 (1973). AO El-Shabrawy, PL Schiff, Jr., DJ Slatkin, B DasGupta, AB Ray, and VJ Tripathi, Heterocycles 22, 993 (1984). J Saez, E Fernandez, A Jossang, A Cave\ and A Cave"., Can. J. Chem. 67, 275 (1989). M Bohlke, H Guinaudeau, CK Angerhofer, V Wongpanich, DD Soejarto, and NR Farnsworth, J. Nat. Prod. 59,576(1996). B Tantisewie, T Pharadai, AJ Freyer, H Guinaudeau, and M Shamma, J. Nat. Prod. 53, 553 (1990). X-X Zhang, Z-J Tang, Y-L Gao, R Chen, A-l Lao, and C-G Wang, Chih Wu Hsueh Pao 23, 216 (1981); Chem. Abstr. 95, 192262 (1981). M Scholtz, Chem. Ber. 29, 2054 (1896). Academica Sinica, K o Hsueh T'ung Pao 24, 574 (1979); Chem. Abstr. 91, 181330 (1979). G Zhang and T Liu, Zhonghua Xixueguanbing Zazhi 11, 224 (1983); Chem. Abstr. 100, 61536 (1984). TR Govindachari and N Viswanathan, Ind. J. Chem. 5, 655 (1967). R Hocquemiller, P Cabalion, A Bouquet, and A Cave*, Compt. Rend. Acad. Sci. Ser. C 285, 447 (1977). R Hocquemiller, P Cabalion, A Fournet, and A Cave\ Planta Med. 50, 23 (1984). M Tomita, H Furukawa, M Junichi, and S Lu, Yakugaku Zasshi 87, 1285 (1967); Chem. Abstr. 68, 36765 (1968). FAL Anet, GK Hughes, and E Ritchie, Aust. J. Sci. Res. 3A, 346 (1950); Chem. Abstr. 45, 822 (1951). M Tomita, H Furukawa, and K Fukagawa, Yakugaku Zasshi 87, 793 (1967). M Tomita, M Junichi, and H Furukawa, Yakugaku Zasshi 87, 1560 (1967); Chem. Abstr. 68, 84980 (1968). GA Swan, An Introduction to the Alkaloids, p 34, John Wiley and Sons, New York (1967). S Lai, TF Zhao, and XK Wang, Acta Pharm. Sinica 23, 356 (1988). X-K Wang, T-F Zhao, S Lai, Y Shizuri, and S Yamamura, Phytochemistry 33, 1448 (1993). D Dwuma-Badu, JSK Ayim, CA Mingle, AN Tackie, DJ Slatkin, JE Knapp, and PL Schiff, Jr., Phytochemistry 14, 2520 (1975). A Roychoudhury, Sci. Culture 38, 358 (1972); Chem. Abstr. 78, 82058 (1973). F Zhou, F Liang, J Fang, K Zhang, C Liang, A Tian, X Fang, Z Shi, and Z Gu, Yaoxue Tongbao 17, 135 (1982); Chem. Abstr. 97, 60870 (1982). T Kikuchi and K Bessho, Yakugaku Zasshi 78, 1408 (1958); Chem. Abstr. 53, 7219 (1959). F-H Chou, C-C Chen, P-Y Liang, and C Wen, Yao Hsueh Tung Pao 16, 50 (1981); Chem. Abstr. 95, 121036(1981). M Bebray, M Plat, and JL Man, Ann. Pharm. Fr. 24, 551 (1966); Chem. Abstr. 66, 28942 (1967). A Bouquet and A Cave", Plant Med. Phytother. 5, 131 (1971); Chem. Abstr. 75, 85207 (1971). C Galeffi, GB Marini-Bettolo, and D Vecchi, Gazz. Chim. Ital. 105, 1207 (1975). BD Gupta, SK Bannerjee, and KL Handa, Phytochemistry 15, 576 (1976). C Galeffi, R LaBua, 1 Messana, RZ Alcazar, GB Marini-Bettolo, Gazz. Chim. Ital. 108, 97 (1978). SM Kupchan, WL Asbun, and BS Thyagarajan, J. Pharm. Sci. 50, 819 (1961). H King, J. Chem. Soc. 1947, 936 (1947). MP Cava, J Kunitomo, and AI Darocha, Phytochemistry 8, 2341 (1969). S Bhattacharji, VN Sharma, and ML Dhar, J. Sci. Ind. Res. I5B, 363 (1956). LJ Haynes, EJ Herbert, and JR Plimmer, J. Chem. Soc. C 1966, 615 (1966). M Tomita and H Shirai, J. Pharm. Soc. Japan 62, 381 (1942); Chem. Abstr. 45, 8540 (1951). II Shchelchkova, TN Ilinskaya, and AD Kuzovkov, Khim. Prir. Soedin. 1965, 271 (1965); Chem. Abstr. 64,6709(1966). DS Bhakuni and S Gupta, J. Nat. Prod. 45, 407 (1982). T Ogino, T Sato, H Sasaki, M Chin, and H Mitsuhashi, Heterocycles 27, 1149 (1988). F Scheinmann, EFV Scriven, and ON Ogbeide, Phytochemistry 19, 1837 (1980). H Guinaudeau, M Leboeuf, M Debray, A Cave\ and RR Paris, Planta Med. 27, 304 (1975).

278 210. 211. 212. 213. 214. 215. 216. 217. 218. 219. 220. 221. 222. 223. 224. 225. 226. 227. 228. 229. 230. 231. 232. 233. 234. 235. 236. 237. 238. 239. 240. 241. 242. 243. 244. 245. 246. 247. 248. 249. 250. 251.

P.L.Schifr,Jr. L-Z Lin, H-L Shieh, CK Angerhofer, JM Pezzuto, GA Cordcll, L Xue, ME Johnson, and N Ruangrungsi, J. Nat. Prod. 56, 22 (1993). B Tantisewie, K Pharadai, S Amnauypol, AJ Freyer, H Guinaudcau, and M Shamma, Tetrahedron 46, 325 (1990). M Parvez, H Guinaudeau, and M Shamma, Acta Cryst. C47. 448 (1991). AS Howard, J Harley-Mason, IRC Bick, Aust. J. Chem. 43, 1129 (1990). J Guilhem and IRC Bick, J. Chem. Soc, Chem. Commun, 1007 (1981). IRC Bick, Private Communication, December 14, 1981. Y lnubushi, Pharm. Bull. (Tokyo) 3, 384 (1955). XP Pang, YW Chen, XJ Li, and JG Long, Acta Pharm. Sinica 26, 387 (1991). C Slguineau, P Richomme, A Foumet, H Guinaudeau, and J Brandon, Plant Med. 57, 581 (1991). RHF Manske, Can. J. Res. 2IB, 17 (1943). RW Doskotch and JE Knapp, Lloydia 34, 292 (1971). M Tomita, Y Okamoto, Y Nagai, K Kitayama, and H Yanagawa, Yakugaku Zasshi 90, 1178 (1970). M Tomita, Y Okamoto, Y Nagai, S Tanaka, and T Hayata, Yakugaku Zasshi 90, 1182 (1970). X-W Zheng, Z-D Min, and S-X Zhao, ICo Hscuh Tung Pao 24, 285 (1979); Chem. Abstr. 91, 27216 (1979). X Guan, W Wang, X Sun, C Zhao, and J Hu, Wuhan Yixueyuan Xuebao 12, 195 (1983); Chem. Abstr. 99, 145990 (1983). S-M Hu, S-X Xu, X-S Yao, C-B Cui, Y Tezuka, and T Kikuchi, Chem. Pharm. Bull. 41. 1866 (1993). P Xiping, Faming Zhuanli Shenqing Gongkai Shuomingshu CN 1,047,861 (1990); Chem. Abstr. 115,99258 (1991). XP Pan, XJ Li, YW Chen, and F Chen, Tianran Chanwu Yanjiu Yu Kaifa 5, 30 (1993); Chem. Abstr. 102, 240160 (1994). Y Sugimoto, A Yoshida, S Uchida, S inanaga, and Y Yamada, Phytochemistry 36, 679 (1994). A Jossang, M Leboeuf, A Cave\ and T Sevenet, J. Nat. Prod. 49, 1018 (1986). P Dute, J-F Weber, A Fournet, A Cave\ and J Bruneton, Phytochemistry 26, 2136 (1987). A Jossang, M Leboeuf, P Cabalion, and A Cave\ Planta Med. 49, 20 (1983). S-T Lu, l-L Tsai, and S-P Leou, Phytochemistry 28, 615 (1989). H Guinaudeau, M Bashir, MD Colton, AJ Freyer, M Shamma, K Jehan. A Nilofar, and A-U Rahman, Phytochemistry 26, 829 (1987). IRC Bick, HM Leow, and S Sotheeswaran, Tetrahedron Lett 1975, 2219 (1975). B Kanyinda, R Vanhaelen-Fastre, and M Vanhaelen, J. Nat. Prod. 58, 1587 (1995). PJ Hearst, J. Org. Chem. 29, 466 (1964). R Torres, FD Monache, and GB Marini-Bettolo, Gazz. Chim. Ital. 109, 567 (1979). R Torres Gaona, Contrib. Cient. Tecnol. (Univ. Tec. Estado Santiago) 11, 7 (1981); Chem. Abstr. 97,52533 (1982). R Torres, Bol. Soc. Chil. Qiiim. 34, j j (jogo). R Ahmed and MP Cava, J. Org. Chem. 42, 2271 (1977). SF Hussain, H Guinaudeau, AJ Freyer, and M Shamma, J. Nat. Prod. 48, 962 (1985). Y Tagashira, R Fujiwara, M Ono, K Ohashi.Y Kamikawa, N Tanaka, H Miwa, T Mannami, E Konaga, et al., Gan to Kagaku Ryoho 8, 234 (1981); Chem. Abstr. 95, 73702 (1981). L-C Lin, C-C Sung, C-Y Fan, C-F Tu, M-L Chou, C-C Ma, and J-S Hsu, YaoHsueh Tung Pao 15, 46 (1980); Chem. Abstr. 95, 86196 (1981). W-N Wu, JL Beal, R-P Leu, and RW Doskotch, Lloydia 40, 384 (1977). Y Lu, Zhongcaoyao 15, 195 (1984); Chem. Abstr. 101, 187944 (1984). W-N Wu, JL Beal, and RW Doskotch, Lloydia 40, 281 (1977). W-N Wu, JL Beal, and RW Doskotch, J. Nat. Prod. 43, 372 (1980). J Kunitomo, Y Murakami, M Oshitaka, M Akasu, K Kodama, N Takeda, K Harada, M Suzuki, A Tatematsu, E Kawanabe, and H Ishii, Chem. Pharm. Bull. 33, 133 (1985). A Patra, TK Mandal, PK Mukhopadhyay, and BC Rami, Phytochemistry 27, 653 (1988). J Wu, JL Beal, and RW Doskotch, J. Org. Chem. 45, 213 (1980). W Snedden, RB Parker, and C Gorinsky, Org. Mass Spectr. 4, 607 (1970).

The Blsbenzylisoquinoline Alkaloids - A Tabular Review 252. 253. 254. 255. 256. 257. 258. 259. 260. 261. 262. 263. 264. 265. 266. 267. 268. 269. 270. 271. 272. 273. 274. 275. 276. 277. 278. 279. 280. 281. 282. 283. 284. 285. 286. 287. 288. 289. 290. 291.

279

L Sheng, T Zhao, X Wang, Y Shizuri, and S Yamamura, Huaxue Xuebao 51, 1133 (1993); Chem. Abstr. 120, 129507 (1994). NT Nghia, I Valka, E Wcigl, V Simanek, D Cortes, and A Cave, Fitoterapia 62, 315 (1991). H Dehaussy, M Tits, and L Angenot, Planta Med. 49, 25 (1983). IRC Bick, JB Bremner, HM Leow, and P Wiriyachitra, J. Chem. Soc. Perkin Trans. 1 1972, 2884 (1972). D Dwuma-Badu, JSK Ayim, NY Fiagbe, AN Tackie, JE Knapp, DJ Slatkin, and PL Schiff, Jr. Lloydia 39, 213(1976). P Pachaly and TJ Tan, Arch. Pharm. 319, 872 (1986). P Pachaly and TJ Tan, Arch. Pharm. 319, 841 (1986). RA Paris and J Le Men, Ann. Pharm. Fr. 13, 200 (1955); Chem. Abstr. 49, 11959 (1959). IRC Bick, GK Douglas, and WI Taylor, J Chem. Soc. C 1969, 1627 (1969). K Tanaka, J. Pharm. Soc. Japan 64, 27 (1944); Chem. Abstr. 45, 5173 (1951). AB Ray, SK Chattopadhyay, RM Tripathi, SS Gambhir, and PK Das, Planta Med. 35, 167 (1979). M Tomita and T Ibuka, Yakugaku Zasshi 83, 996 (1963); Chem. Abstr. 60, 4201 (1964). DHR Barton, GW Kirby, and A Wiechers, J. Chem. Soc. C 1966, 2313 (1966). MR Falco, JX Devries, Z Maccio, and IRC Bick, Experientia 25, 1236 (1969). C Goepel, T Yupraphat, P Pachaly, and F Zymalkowski, Planta Med. 26, 94 (1974). SM Kupchan, N Yokoyama, and BS Thyagarajan, J. Pharm. Sci. 50, 154 (1961). M Tomita, M Kozuka, and S Lu, Yakugaku Zasshi 87, 316 (1967); Chem. Abstr. 67, 32855 (1967). T Hu and S Zhao, Acta Pharm. Sinica 21, 29 (1986). D Cai, M gu, X Chen, and J Zhang, Zhongcaoyao 24, 339 (1993); Chem. Abstr. 120, 14982 (1994). S Ratsimamanga-Urverg, P Rasoanaivo, L Ramiaramanana, R Milijaona, R.; H Rafatro, F Verdier, A Rakoto-Ratsimamanga, and J Le Bras, Planta Med. 58, 540 (1992). P Rasoanaivo, S Ratsimamanga-Urverg,and A Rakoto-Ratsimamanga, Biochem. Syst. Ecol., 23,679 (1995). T Ogino, S Sato, H Sasaki, and M Chin, Jpn. Kokai Tokkyo Koho JP 62,205,084 [87,205,084] (1987); Chem. Abstr. 109, 79696 (1988). T Ogino, S Sato, H Sasaki, and M Chin, Jpn. Kokai Tokkyo Koho JP 62,294,684 (87,294,684) (1987); Chem. Abstr. 109, 55030 (1988). AN Tackie, D Dwuma-Badu. JSK Ayim, TT Dabra, JE Knapp, DJ Slatkin, and PL Schiff, Jr. Lloydia 38, 210(1975). AN Tackie, D Dwuma-Badu, JE Knapp, and PL Schiff, Jr. Lloydia 36. 66 (1973). AN Tackie, JB Reighard, MM El-Azizi, DJ Slatkin, PL Schiff, Jr., and JE Knapp, Phytochemistry 19, 1882 (1980). D Dwuma-Badu, TU Okarter, AN Tackie, JA Lopez, DJ Slatkin, JE Knapp, PL Schiff, Jr., J. Pharm. Sci. 66, 1242 (1977). D Cortes, H Dadoun, RL Ribeiro Paiva, and AB De Oliveira, J. Nat. Prod. 50, 910 (1987). D Dwuma-Badu, JSK Ayim, AN Tackie, PD Owusu, JE Knapp, DJ Slatkin, and PL Schiff, Jr., Heterocycles 9,995(1978). PD Owusu, DJ Slatkin, JE Knapp, and PL Schiff, Jr., J. Nat. Prod. 44, 61 (1981). M-C Chalandre, J Bruneton, P Cabalion, and H Guinaudeau, J. Nat. Prod. 49, 101 (1986). P Damas, J Bruneton, A Fournet, and H Guinaudeau, J. Nat. Prod. 48, 69 (1985). ZF Ismailov, D Sargazakov, and SYu Yunusov, Dokl. Akad. Nauk Uz. SSR, 32 (1960); Chem. Abstr. 61, 4700(1964). S Yu Yunusov and MV Telezhenetskaya, Dokl. Akad. Nauk Uz. SSR 20, 22 (1963); Chem. Abstr. 61, 14735 (1964). L Lin, J Zhang, C Xu, and Z Chen, Zhongcaoyao 18, 2 (1987); Chem. Abstr. 107, 93538 (1987). CG Gao, YE AH, M Sharaf, LK Wong, EW Fu, F-T Lin, FK Duah, and PL Schiff, Jr., Phytochemistry 29, 1895(1990). M Shamma, RJ Shine, and BS Dudock, Tetrahedron 23, 2887 (1967). M Velcheva, H Dutschewska, and G Samuelsson, Acta Pharm. Nord. 4, 57 (1992). M Velcheva, Kh Duchevska, B Kuzmanov, S Dangaagiin, Z Samdangiin, and Z Yansangiin, Dokl. Bolg. Akad. Nauk. 44, 33 (1991); Chem. Abstr. 116, 80438 (1992). Z-C Lou, C-Y Gao, F-T Lin, J Zhang, M-C Sharaf, LK Wong, DJ Slatkin, and PL Schiff, Jr., Planta Med. 58, 114(1992).

280 292. 293. 294. 295. 296. 297. 298. 299. 300. 301. 302. 303. 304. 305. 306. 307. 308. 309. 310. 311. 312. 313. 314. 315. 316. 317. 318. 319. 320. 321. 322. 323. 324. 325. 326. 327. 328. 329. 330. 331. 332. 333. 334. 335. 336. 337. 338.

P.L.Schifr,Jr. C Rao, PL Zhang, WM Chen, QC Fang, Chung Ts'ao Yao 8, 344 (1989). J Padilla and J Herran, Tetrahedron 18, 427 (1962). JA Ldpez, M-c Lin, and PL Schifif, Jr., Phytochemistry 27, 3335 (1988). HHS Fong, JL Beal, and MP Cava, Lloydia 29, 94 (1966). NM Mollov and VSt Georgiev, C. R. Acad. Bulg. Sci. 20, 329 (1967). S Abdizhabbarova, SKh Maekh, and SYu Yunusov, Khim. Prior. Soedin. 1978, 139 (1978); Chem. Abstr. 89, 39368 (1978). S Abdizhabbarova, SKh Maekh, and SYu Yunusov, Chem. Natl. Compounds 14, 114 (1978). S Mukhamedova, SKh Maekh, and SYu Yunusov, Khim. Prir. Soedin. (2), 250 (1981); Chem. Abstr. 95, 58078 (1981). KHC Baser, M Ogutveren, and NG Bisset, J. Nat. Prod. 48, 672 (1985). R Verpoorte, J Siwon GFA van Essen, M Tieken, and AB Svendsen, J. Nat. Prod. 45, 582 (1982). M Tomita, M Kozuka, and M Satomi, Yakugaku Zasshi 87, 1012 (1967); Chem. Abstr. 68, 3052 (1968). Z-J tang, A-N Lao, Y Chen, X X Zhang, CG Wang, and FD Zhong, Yao Hsueh Hsueh Pao 15, 506 (1980); Chem. Abstr. 94, 202753 (1981). J-Z Deng, S-X Zhao, and Z-C Miao, Nat. Prod. Lett. 2, 283 (1993). LA Mitscher, W-N Wu, and JL Beal, Experientia 28, 500 (1972). B Charles, J Bruneton, K Pharadai, B Tantisewie, H Guinaudeau, and M Shamma, J. Nat. Prod. 50, 1113 (1987). SF Hussain, AJ Freyer, H Guinaudeau, and M Shamma, J. Nat. Prod., 49 488 (1986). X Fang, L Qian, P Shen, and Z Shi, Zhongcaoyao 16, 536 (1985); Chem. Abstr. 104, 145508 (1986). X-K Wang, T-F Zhao, S Lai, Y Shizuri and S Yamamura, Phytochemistry 33, 1448 (1993). M Satomi, Ann. Rept. ITSUU Lab. (Japan) 6, 31 (1955); Chem. Abstr. 50, 10112 (1956). K Bodendorf and W Scheibe, Arch. Pharm. 287, 551 (1954). JA Barltrop and JAD Jeffreys, J. Chem. Soc. 1954, 159 (1954). MA Ferreira, LN Prista, AC Alves, and AS Roque, Garcia Orta. 13, 395 (1965); Chem. Abstr. 67, 100295 (1967). RR Paris and SK Sasorith, Ann. Pharm. Fr. 25, 627 (1967). M Tomita and T Kikuchi, J. Pharm. Soc. Japan 77, 69 (1957); Chem. Abstr. 51, 9646 (1957). M Tomita, H Furukawa, TH Yang, and TJ Lin, Tetrahedron Lett. 1964, 2637 (1964). S Nishibe, H Tsukamoto, H Kinoshita, S Kitagawa, and A Sakushima, J. Nat. Prod. 49, 547 (1986). IRC Bick and WI Taylor, J. Chem. Soc. C 1971, 3779 (1971). V Fajardo, A Leon, MC Loncharic, V El an go, M Shamma, and BK Cassels, Bol. Soc. Chil. Quim. 27, 159 (1982); Chem. Abstr. 96, 214302 (1982). V Hrochova and D Kostalova, Cesk. Farm. 41, 37 (1992). A Karimov, MG Levkovich, ND Abdullaev, and R Shakirov, Chem. Nat. Compounds, 29 331 (1993). A Urzua and R Torres, Fitoterapia 64, 378 (1993). C Moulis, J. Nat. Prod. 44, 101 (1981). E Bianchi, JA Garbarino, and F Giora, Gazz. Chim. ltal. 92, 818 (1962); Chem. Abstr. 58, 4614 (1963). G Schemda-Hirschmann, M Dutra-Bchrens, G Habermehl, and J Jakupovic, Phytochemistry 41, 339 (1996). M Tomita and M Sugamoto, Yakugaku Zasshi 81, 1090 (1961); Chem. Abstr. 56, 3564 (1962). N Ruangrungsi, W De-Eknamkul, and GL Lange, Planta Med. 50, 432 (1984). AN Tackie, D Dwuma-Badu, JE Knapp, and PL SchiiT, Jr., Phytochemistry 12, 203 (1973). VJ Tripathi, AB Roy, and B Dasgupta, Ind. J. Chem. 14B, 62 (1976). VU Ahmad and T Rashid, J. Chem. Soc. Pak. 8, 537 (1986); Chem. Abstr. 106, 99448 (1987). VU Ahmad and S Iqbal, Nat. Prod. Lett. 2, 105 (1993). M Tomita and H Furukawa, Yakugaku Zasshi 83, 190 (1963); Chem. Abstr. 59, 3971 (1963). CT Fu, Shan-hsi Hsin 1 Yao 10, 49, 55 (1981); Chem. Abstr. 96, 11548 (1982). NK Hart, SR Jones, JA Lamberton, and H Suares, Aust. J. Chem. 25, 2289 (1972). M Tomita and S Ueda, Yakugaku Zasshi 79, 977 (1959); Chem. Abstr. 53, 22042 (1959). IRC Bick and HM Leow, Aust. J. Chem. 31, 2539 (1978). MR Falco, JX Devries, AG Debrovetto, Z Maccio, S Rebuffb, and IRC Bick, Tetrahedron Lett. 1968, 1953 (1968). Y Chao, Y Chou, P Yang, and C Chou, Sci. Sinica 11, 215 (1962); Chem. Abstr. 57, 7383 (1962).

The Bisbenzyllsoqninoline Alkaloids - A Tabular Review 339. 340. 341. 342. 343. 344. 345. 346. 347. 348. 349. 350. 351. 352. 353. 354. 355. 356. 357. 358. 359. 360. 361. 362. 363. 364. 365. 366. 367. 368. 369. 370. 371. 372. 373. 374. 375. 376. 377. 378. 379. 380.

281

H Furukawa, Yakugaku Zasshi 85, 353 (1965); Chcm. Abstr. 63, 4351 (1965). X Hu, B Zhou, S Luo, H Cai, and W Yin, Zhongcaoyao23, 575 (1992); Chem. Abstr. 118, 56229 (1993). J Wang, X Hu, W Yin, and H Cai, Zhongguo Zhongyao Zazhi 16, 673 (1991); Chem. Abstr. 116, 124932 (1992). BA Fasihuddin, V Shanty, and MS Atan, Pertanika 14, 355 (1991); Chcm. Abstr. 118, 98072 (1993). ST Lu and IS Chen, Heterocycles 4, 1073 (1976). NF Proskurnina and AP Orekhov, Bull. Soc. Chim. 5, 1357 (1938). J Bruneton, M Shamma. RD Minard, AJ Freyer, and H Guinaudeau, J. Org. Chem. 48, 3957 (1983). JJ Chen, IL Tsai, YL Chang, and CM Teng, Planta Med. 61, 537 (1995). I-S Chen, J-J Chen, and I-L Tsai, Phytochemistry, 40, 983 (1995). D Cortes, J Saez, R Hocquemiller, A Cave\ and A Cave\ Heterocycles 24, 607 (1986). A Sinha, J. Proc. Inst. Chem. (India), 32, 250 (1960); Chem. Abstr. 55, 18886 (1961). TQ Chou, Chin. J. Physiol. 9, 267 (1935); Chem. Abstr. 30, 471 (1936). AM Karimov, MV Telezhenetskaya, KL Lutrullin, and SYu Yunusov, Khim. Prir. Soedin., 1978, 227 (1978). A Karimov, MV Telezhenetskaya, KL Lutrullin, and S Yu Yunusov, Chem. Natl. Compounds 14, 186 (1978). N El-Sebakhy and PG Waterman, Phytochemistry 23, 2706 (1984). R Tschesche, R Goepel, and H-W Fehlhaber, Phytochemistry 9, 1683 (1970). J Deng, S Zhao, and F Lou, J. Nat. Prod. 53, 993 (1990). MUS Sultanbawa, S Sotheeswaran, S Balasubramaniam, M Abd El-Kawi, DJ Slatkin, and PL Schiff, Jr., Heterocycles 20, 1927(1983). MUS Sultanbawa, S Sotheeswaran, S Balasubramaniam, M Abd El-Kawi, DJ Slatkin, and PL SchitT, Jr., Phytochemistry 24, 589 (1985). B Kanyinda, R Vanhaelen-Fastre\ and M Vanhaelen, J. Nat. Prod. 59, 498 (1996). H Wagner, LZ Lin, and O Seiigmann, Planta Med. 50, 14 (1984). W-N Wu, W-T Liao, ZF Mahmoud, JL Beal, and RW Doskotch, J. Nat. Prod. 43, 472 (1980). R Ahmad, Islamabad J. Sci. 5, 38 (1978). M Kurbanov, YuM Nuraliev, M Khodzhimatov, and MD Isobaev, Rastit. Resur. 20, 125 (1984); Chem. Abstr. 100, 117850(1984). S Mukhamedova, SKh Maekh, and SYu Yunusov, Chem. Nat. Cpds. 20, 246 (1984). HV Dutschweska, AV Georgieva, NM Mollov, PP Panov, and NK Kotsev, Dokl. Bolg. Acad. Nauk 24,467 (1971). NM Mollov, PP Panov, TL Nhat, and L Panova, Dokl. Bolg. Acad. Nauk 22, 181 (1970); Chem. Abstr. 73, 32285 (1970). S Yunuvov and NN Progressov, Zhur. Obshchei Khim. 20, 1151 (1950); Chem. Abstr. 45, 1608 (1951). S Yu Yunusov and ZF Ismailov, Dokl. Akad. Nauk Uzbek SSR 17(1956); Chem. Abstr. 52, 12100(1958). H Dutschewska, B Dimov, N Mollov, and L Evstatieva, Planta Med. 39, 77 (1980). S Mukhamedova, SKh Maekh, and SYu Yunusov, Chem. Nat. Cpds. 19, 375 (1983). DA Murav'eva,ON Tolkachev, and A A Akopov, Khim. Prir. Soedin, 416 (1985); Chem. Abstr. 103, 51227 (1985). M Popovie, R Djurkovit, O GaSic\ B Pal, H Dutschewska, and B Kuzmanov, Biochem. Syst. and Ecol. 20, 255(1992). Z Wu, T Wu, T Jin, and Y Wang, Zhongguo Yaoke Daxue Xuebao 19, 203 (1988); Chem. Abstr. 109, 208351 (1988). N Kirimer and KHC Baser, Planta Med. 57, 587 (1991). KHC Baser, Doga, Sen A 5, 163 (1981); Chem. Abstr. 96, 65701 (1982). KHC Baser and N Kirimer, Planta Med. (5), 448 (1985). W-N Wu, JL Beal, and RW Doskotch, Lloydia 40, 508 (1977). J Wu, JL Beal, W-N Wu, and RW Doskotch, J. Nat. Prod. 43, 270 (1980). E Fujita and T Tomimatsu, Yakugaku Zasshi 79, 1256 (1959); Chem. Abstr. 54, 4643 (1960). B Dimov, Kh Duchevska, and B Kuzmanov, Compt. Rend. Acad. Bulg. Sci. 42, 61 (1989). S Mukhamedova, SKh Maekh, and SYu Yunusov, Chem. Nat. Cpds. 20, 377 (1984).

282

P.L.Schiff,Jr.

381.

AK Ray, G Mukhopadhyay, SK Mitra, KP Guha, B Mukherjee, A-ur-Rahman, and A Nelofar, Phytochemistry 28, 675 (1989). AK Ray, G Mukhopadhyay, SK Mitra, KP Guha, B Mukhcrjee, A-U Rahman, A Nelofar, Phytochemistry 29, 1020(1990). B Hoffstadt, D Moecke, P Pachaly, and F Zymalkowski, Tetrahedron 30, 307 (1974). IRC Bick, HM Leow, NW Preston, and JJ Wright, Aust. J.Chem. 26, 455 (1973). P Pachaly and H Khosravian, Planta Med. 54, 433 (1988). MP Cava, JM Saa, MV Lakshmikantham, and MJ Mitchell, J. Org. Chem. 40, 2647 (1975). IRC Bick, J Harley-Mason, and MJ Vernengo, Anales Asoc. Quin. Arg. 5, 135 (1963). KC Chan, MTA Evans, CH Hassal, and AMW Sangster, J. Chem. Soc. C 1967, 2479 (1967). JM Saa, MJ Mitchell, MP Cava, and JL Beal, Heterocycles 4, 753 (1976). KHC Baser and N Kirimer, Planta Med. 54, 513 (1988). AN Tackie and A Thomas, Planta Med. 16, 158 (1968). KP Guha, PC Das, B Mukherjee, R Mukhcrjee, GP Juneau, and NS Bhacca, Tetrahedron Lett. 47, 4241 (1976). B Anjaneyulu, TR Govindachari, SS Sathe, N Viswanathan, KW Gopinath, and BR Pai, Tetrahedron 25, 3091 (1969). DS Bhakuni, AN Singh.and S Jain, Tetrahedron 37, 2651 (1981). H Guinaudeau, AJ Freyer, M Shamma, SK Mitra, AK Roy, and B Mukherjee, J. Nat. Prod. 48, 651 (1985). P Singh, VB Pandey, YC Tripathi, and UP Singh, Pflanzenkrankh. Pflanzenschutz 98, 213 (1991); Chem. Abstr. 115, 129882(1991). P Wiriyachitra and B Phuriyakorn, Aust. J. Chem. 34, 2001 (1981). P Pachaly, TJ Tan, H Khosravian, and M Klein, Arch. Pharm. 319. 126 (1986). M Abd El-Kawi, DJ Slatkin. PL Schiff, Jr., S DasGupta, SK Chattopadhyay, and AB Ray, J. Nat. Prod. 47, 459(1984). M Tomita and T kugo, Yakugaku Zasshi 79, 317 (1959); Chem. Abstr. 53, 17161 (1959). S-T Lu and E-C Wang, J. Taiwan Pharm. Assn. 29, 49 (1977). BK Cassels, and A Urzua, J. Nat. Prod. 48, 671 (1985). TA Suess and FR Stermitz, J. Nat. Prod. 44, 680 (1981). W-T Liao, JL Beal, W-N Wu, and RW Doskotch, Lloydia 41, 257 (1978). M Tomita and T Ibuka, Yakugaku Zasshi 83, 940 (1963); Chem. Abstr. 60, 4202 (1964). LA Mitscher, W-N Wu, RW Doskotch, and JL Beal, Lloydia 35. 167 (1972). JE Knapp, FT Hussein, JL Beal, RW Doskotch, and T Tomimatsu, J. Pharm. Sci. 56, 139 (1967). D Cortes, R Hocquemiller, A Cave, J Saez, and A Cave\ Can. J. Chem. 64, 1390 (1986). MP Cava, KT Buck, and KL Stuart in: The Alkaloids, Vol. 16, pp. 249, The Bisbenzylisoquinoline Alkaloids - Occurrence, Structure and Pharmacology, RHF Manske, Ed., Academic Press, New York (1977). T Hu, S Zhao, D Lin, Z Yao, and RF Chandler, Int. J. Crude Drug Res. 26, 1 (1988). E Spilth and A Kolbe, Chem. Ber. 58, 2280 (1925). A Karimov, VI Vinogradova, and R Shakirov, Chem. Nat. Compounds 29, 57 (1993). A Karimov, S Melliboev, V Olimov, and R Shakirov, Chem. Nat. Compounds 29, 412 (1993). A Karimov and RSh Shakirov, Chem. Nat. Compounds 29, 524 (1993). N Pant, HS Garg, and DS Bhakuni, Fitoterapia 57, 427 (1986). L Beauquesne, Bull. Sci. Pharmacol. 45, 7 (1938); Chem. Abstr. 32, 3089 (1938). IK Said, A Latiff, SJ Partridge, and JD Phillipson, Planta Med. 57, 389 (1991). K Ito, Yakugaku Zasshi 80, 705 (I960); Chem. Abstr. 54, 18887 (I960). R Chaterjee and MP Guha, Sci. and Culture 15, 163 (1949); Chem. Abstr. 44, 2706 (1950). R Chatterjee, MP Guha, and SK Sen, J. Am. Pharm. Assoc. 40, 36 (1951). R Chatterjee and MP Guha, J. Am. Pharm. Assoc. 40, 229 (1951). LR Row and ASR Anjaneyulu, J. Sci. Ind. Res. 2IB, 581 (1962). AC Santos, Rev. Filip. Med. Farm. 22, 11 (1931); Chem. Abstr. 26, 729 (1932). JR Boissier, A Bouquet, G Combes, C Dumont, and M Debrey, Ann. Pharm. Fr. 21, 767 (1963); Chem. Abstr. 60, 6701 (1964). MP Cava, K Wakisaka, I Noguchi, DL Edie, and AI Darocha, J. Org. Chem. 39, 3588 (1974).

382. 383. 384. 385. 386. 387. 388. 389. 390. 391. 392. 393. 394. 395. 396. 397. 398. 399. 400. 401. 402. 403. 404. 405. 406. 407. 408. 409.

410. 411. 412. 413. 414. 415. 416. 417. 418. 419. 420. 421. 422. 423. 424. 425.

The Bisbenzyllsoqutnoline Alkaloids - A Tabular Review 426. 427. 428. 429. 430. 431. 432. 433. 434. 435. 436. 437. 438. 439. 440. 441. 442. 443. 444. 445. 446. 447. 448. 449. 450. 451. 452. 453. 454. 455. 456. 457. 458. 459. 460. 461. 462. 463. 464. 465. 466. 467. 468. 469.

283

IRC Bick and TG Whalley, Univ. Queensland Papers. Dept. Chem. 1, 8 (1948); Chcm. Abstr. 41, 1390 (1947). J Wu, JL Beal, WN Wu, and RW Doskotch, J. Nat. Prod. 43, 270 (1980). K Takahashi, MJ Mitchell, and MP Cava, Heterocycles 4, 471 (1976). K Takahashi and MP Cava, Heterocycles 5, 367 (1976). D Cortes, J Saez, R Hocquemiller, and A Cave\ C.R. Acad. Sci. 298, 591 (1984). M Matsui, ToKobashima, K Ishida, T Takebayashi, and Y Watanabe, J. Nat. Prod. 45, 497 (1982). H Guinaudeau, BK Cassels, and M Shamma, Heterocycles 19, 10090 (1982). G Ruecker and R Mayer, Plant Med. 51, 183 (1985). GR Choudhury and ML Dhar, J. Sci. Ind. Res. 17B, 163 (1958); Chem. Abstr. 52, 20454 (1958). K Kubota, T Ogino, H Sasaki, and M Chin, Jpn. Kokai Tokkyo Koho JP 62,209,0I8[87,209,0I8] (1987); Chcm. Abstr. 108, 173549 (1988). DY Si, SX Zhao, and JZ Deng, J. Nat. Prod. 55, 828 (1992). S Abdizhabbarova, ZF Ismailov, and S Yu Yunusov, Khim. Prir. Soedin. 4, 330 (1968); Chem. Abstr. 70, 75086 (1969). S Mukhamedova, SKh Maekh, and SYu Yunusov, Chem. Nat. Cpds. 19, 376 (1983). Z Wu and Y Yi, Zhongguo Yaoke Daxue Xuebao 22, 177 (1991); Chem. Abstr. 115, 275734 (1991). Y Zhou, Y Guo, and X Meng, Shenyang Yaoxueyuan Xuebao 7, 45 (1990); Chem. Abstr. 113, 158513 (1990). JM Saa, MV Lakshmikantham, MJ Mitchell, MP Cava, and JL Beal, Tetrahedron Lett. 1976, 513 (1976). J Wu, JL Beal, and RW Doskotch, J. Org. Chem. 45, 208 (1980). T Tomimatsu and M Sasakawa, Chem. Pharm. Bull. 23, 2279 (1975). SM Kupchan, TH Yang, ML King, and RT Borchardt, J. Org. Chem. 33, 1052 (1968). C-C Ma, Yao Hsueh Tung Pao 15, 46 (1980); Chem. Abstr. 95, 54810 (1981). KHC Baser and A Ertan, Planta Med. 56, 337 (1990). DS Bhakuni and RS Singh. J. Nat. Prod. 45, 252 (1982). Z Wang, Y Guo, and X Meng, Zhongcaoyao 19, 161(1988); Chem. Abstr. 109, 66429 (1988). W-N Wu, JL Beal, EH Fairchild, and RW Doskotch, J. Org. Chem. 43, 580 (1978). S Al-Khalil and PL SchifT, Jr., J. Nat. Prod. 25, 935 (1986). SK Chattopadhyay, AB Ray, DJ Slatkin, JE Knapp, and PL SchifT, Jr., J. Nat. Prod. 44, 45 (1981). Kh G Pulatova, S Kh Maekh, ZF Ismailov, and S Yu Yunusov, Khim. Prir. Soedin 4, 394 (1968). S Al-Khalil, H Ammar, and A Al-Kofahi, Alexandria J. Pharm. Sci. 8, 195 (1994); Chem. Abstr. 123, 222752(1995). M Sahai, SC Sinha, AB Ray, SK Chattopadhyay, S Al-Khalil, DJ Slatkin, and PL SchifT, Jr. J. Nat. Prod. 48,669(1985). DAMurav'eva,ONTolkachev,andAA Akopov, Khim. Prir. Soedin, 416(1985); Chem. Abstr. 103,51226 (1985). W-N Wu, JL Beal, GW Clark, and LA Mitscher, Lloydia 39, 65 (1976) A Urzua M and S Espinoza S, Rev. Latinoam. Quim. 19, 109 (1988); Chem. Abstr. 110, 132169 (1989). M Matsui, M Uchida, I Usuki, Y Saionji, H Murata, and Y Watanabe, Phytochemistry 18, 1087 (1979). X-K Wang, Y-R Zhao, T-F Zhao, and C-T Che, Planta Med. 61, 99 (1995). M Shamma and SY Yao, Experientia 29, 517 (1973). D Umarova, SKh Maekh, SYu Yunusov, NM Zaitseva, SA Volkova, and PG Gorovoi, Chem. Natl. Compounds 14, 511 (1978). SKh Maekh, ZF Ismailov, and SYu Yunusov, Khim. Prior. Soedin. 4, 138 (1968). SKh Maekh and SYu Yunusov, Khim. Prior. Soedin. 1, 188 (1965); Chem. Abstr. 63, 14929 (1965). AK Barua, P Chakraborty, and AS Duttagupta, J. Ind. Chem. Soc. 47, 920 (1970). JSK Ayim, D Dwuma-Badu, NY Fiagbe, AM Ateya, DJ Slatkin, JE Knapp, and PL SchifT, Jr., Lloydia 40, 561 (1977). P Pachaly and H Khosravian, Planta Med. 54, 516 (1988). KVJ Rao and LR Row, J Sci. Ind. Res. I8B, 247 (1959). D Dwuma-Badu, JSK Ayim, AN Tackie, MA ElSohly, JE Knapp, DJ Slatkin, and PL SchifT, Jr., Experientia 31, 1251 (1975). S Dasgupta, AB Ray, SK Bhattacharya, and R Bose, J. Nat. Prod. 42, 399 (1979).

284

P.L.SchifT,Jr.

470. 471.

H King, J. Chcm. Soc. 1948, 1945 (1948). PL Schiff, Jr., in "Alkaloids: Chemical and Biological Perspectives" Ed. by SW Pelletier, John Wiley and Sons, Inc., New York, 1987, Vol. 5, Chapter 4, pp. 271-637. J-J Chen, I-L Tsai, T Ishidawa, and C-J Wang, Phytochemistry 42, 1479 (1996). FA Hussaini and A Shoeb, Phytochemistry 24, 633 (1985). I Kitagawa, K Minagawa, R-S Zhang, K Hon, M Doi, M Inous, T Ishida, M Kimura, T Uji, and H Shibuya, Chem. Pharm. Bull. 41, 997 (1983). H Tanaka, A Harada, K Ichino, and K Ito, Heterocycles 16, 1275 (1981). Z-L Chen, Hua Hsueh Hsueh Pao 38, 567 (1980); Chem. Abstr. 94, 127204 (1981). N Borkakoti and RA Palmer, Acta Crystallogr., Sect. B B34, 432 (1978). IRC Bick, ES Ewen, and AR Todd, J. Chem. Soc. 1949, 2767 (1949). MV Telezhenetskaya,ZF Ismailov, and SYu Yunusov, Khim. Prir. Soedin. 2, 107 (1966); Chem. Abstr. 65, 10629(1966). MV Telezhenetskayaand S Yu Yunusov, Dokl. Akad. Nauk Uzbek SSR 162,254 (1965); Chem. Abstr. 63, 5689 (1965). NM Mollov and VSt Georgiev, Chem. & Ind. 1966, 1178 (1966). ZA Ismailov, AU Rakhmatkariev, and SYu Yunusov, Uzbeksk, Khim. Zh. 1961. 56 (1961); Chem. Abstr. 58,3469(1963). M Shamma and JL Moniot, Heterocycles 4, 1817(1976).

472. 473. 474. 475. 476. 477. 478. 479. 480. 481. 482. 483.

Chapter Two

Alkaloids from Malaysian Flora Toh-Seok Kam Department of Chemistry University of Malaya 50603 Kuala Lumpur Malaysia

CONTENTS 1.1. INTRODUCTION 1.2. ALKALOID CONTAINING MALAYSIAN PLANTS 1.3. STRUCTURE ELUCIDATION AND CHEMISTRY 1.3.1. Isoquinoline and related alkaloids 1.3.2. Steroidal alkaloids 1.3.3. Monoterpene alkaloids 1.3.4. Indole alkaloids 1.3.5. Bisindole alkaloids 1.3.6. Miscellaneous nitrogenous natural products 1.3.7. Table 3. Alkaloid content of chemically investigated Malaysian plants 1.4. BIOLOGICAL ACTIVITY 1.5. CONCLUSION 1.6. ADDENDUM REFERENCES

286 286 316 316 324 326 329 379 393 395 416 418 419 426

286

T.-S. Kara

1.1. INTRODUCTION Malaysia (incorporating the Malayan Peninsular and Malaysian Borneo) is located in the heart of South East Asia and constitutes part of the Malesian phytogeographical region. Its position near the Equator confers on it a typically tropical climate, characterized by high temperatures, humidity and rainfall throughout the year. Such conditions are conducive to plant life and have resulted in a rich and thriving flora. It is estimated that the country is home to some 15,000 species of higher plants [1,2]. The potential for botanical and chemical studies and for discovery of novel chemical constituents, especially those possessing useful bioactivities is therefore immense. The need for such studies has assumed a greater urgency in recent times in the wake of the threat posed by rapid development and with the growing concern that valuable plant substances which may present useful lead compounds for drug discovery may be lost. The study of alkaloids has always assumed a preeminent position in the early studies by investigators in the late 1960's and 70's. Perhaps this has to do with the easier isolation associated with this group of compounds due to their basic nature, or perhaps the fact that alkaloids invariably possess strong physiological properties presented an added incentive. The early studies were mainly dominated by phytochemical screening of plant samples for the presence of alkaloids, terpenes and saponins [3-10]. Interspersed between these studies were the occasional chemical studies of various plants, mainly with respect to the occurrence and structure of indole alkaloids and usually undertaken with collaboration of better equipped laboratories. With better facilities, the study of natural products and of alkaloids in particular attained greater momentum in the eighties which has continued through to the nineties. This review will concentrate on work published in the last 20 years or so with the exception of a few background papers, since this is the period when most of the work on the chemistry of alkaloids from Malaysian plants have emerged. In writing this review we are mindful of the fact that it is somewhat artificial to suppose that flora are respecters of national boundaries, hence the chemistry of the plants described in this chapter could very well be representative of similar flora found in other parts of the South East Asian region. In view of this, we will as far as possible and wherever appropriate, compare the occurrence of alkaloids with studies of similar plants from neighbouring countries, especially Thailand and Indonesia.

1.2. ALKALOID CONTAINING MALAYSIAN PLANTS There has been a number of phytochemical surveys of Malaysia that have been carried out in the period spanning the last three decades, especially during the earlier period of the sixties and seventies [3-17]. These surveys have provided useful information for subsequent

287

Alkaloids from Malaysian Flora

investigators in cataloging the results of tests for the presence of alkaloids and other constituents. Table 1 summarizes the alkaloid producing species found in Malaysia. The plants are listed systematically under family, genus and species. The alkaloids were detected by the Mayer or Dragendorff reagents or by TLC of an alkaloidal extract followed by detection with the Dragendorff reagent. The test results are cited as strong (s), medium (m), weak (w) or just (+) in cases where a positive result was obtained but no attempt was made to estimate the relative amount. The plant parts examined are abbreviated as follows: L (leaves), B (bark), S (stem), Wd (wood), Sd (seed), F (fruit), Fl (flowers), R (root) and W (whole plant). It is evident from examination of these results as well as from the subsequent chemical studies that have followed that alkaloid rich species predominate in the Families Annonaceae, Apocynaceae and Rubiaceae and to a lesser extent in Lauraceae, Menispermaceae, Verbanaceae, Euphorbiaceae and Rutaceae.

Table 1. Alkaloid-positive plants from phytochemical surveys

Plant Acanthaceae Acanthus ebracteatus Wall. Andrographis paniculata Nees Asystasia nemorum Nees Filetia glabra Ridl. Gendarusa vulgaris Justicia ptychostoma Nees Lepidagathis longifolia Wight Pseuderanthemum graciliflorum Nees Staurogyne lanceolata Kze Thunbergia alata Thunbergia natalensis Hk. f. Actinidiaceae Saurauia nudiflora Aizoacea Sesuvium portulacastrum (L.) L

Plant part

Alkaloid test

References

L,B W W W S,R W R W L,B W L W L W

w +

[in

w w s w s m w w m m + w

[11] [9] [4]

L

w

[16]

W

m

[7]

[6]

[11] [5] [9] [11] [10] [17] [11] [3] [9]

288

T.-S. Kam

Table 1. Alkaloid-positive plants from phytochemical surveys (cont.)

Plant Alangiaceae Alangium griffithii (Clarke) Harms. Amaranthaceae Celosia argentea Anacardiaceae Buchanania lucida Bl. Mangifera caesis Jack, ex Wall.

Melanorrhoea woodsiana Scort. Ancistrocladaceae Ancistrocladus tectorius (Lour.) Merr. Annonaceae Alphonsea cylindrica King Alphonseajohorensis J. Sinclair Alphonsea kinabaluensis J. Sinclair Anaxagorea javanica Bl. Artabotrys blumei Hk. f. & Thorns. Artabotrys crassifolius Hk.f. Artabotrys grandifolius King Artabotrys maingayi Hk. f. Artabotrys suaveolens Bl. Artabotrys venustus King Canangium odoratum Baill. Cyathocalyx pahangensis J. Sinclair

Plant part

Alkaloid test

References

F,Wd

w

[7]

L

+

[3]

S L S S S

w w w m +

[10] [7,9]

L,S

[7]

P] [6] [7]

L B L L B S L S L B B

s m m s m w w m w s m

B B L, S, Fl B B L B

s s +

[11] [11,12]

s + w s

[11] [6]

[11] [12] [11] [10] [10] [11] [11]

[6]

[H]


289


Plant Cyathocalyx scortechinii (King) J. Sinclair Cyathostemma excelsum J. Sinclair Cyathostemma hookeri Cyathostemma wrayi King Desmos chinensis Lour. Desmos dasymaschalus (Bl.) Saff. Desmos dasymaschalus Saff. var. wallichii Disepalum pulchrum (King) J. Sinclair Drepanthus pruniferus Maing. Enicosanthum congregatum (King) Airy-Shaw Enicosanthumfitscum(King) Airy-Shaw Enicosanthum membranifolium Fissistigma lanuginosum Merr. Fissistigma latifolium (Dun.) Merr. Fissistigma manubriatum Merr. Friesodielsia acuminata (Merr.) van Steenis Friesodielsia biglandulosa Friesodielsia calycina Friesodielsia korthalsiana Miq. Goniothalamus curtisii King

Plant part

Alkaloid test

References

B

w

[11]

L,B L S R B L S L,B L,B

w m w s s w m s m

[H] [12] [4] [11] [12] [11] [11]

[in F,S L B L

w w w m

[7] [11,14] [14]

,, Sd, R L B B L,S L,B L

s s m w w w s

[5] [11]

L L L L B L

w w w w m m

[14] [14]

[11]

[11] [12] [11] [H]

[11] [8,11] [8,11,13] [13]

290

T.-S. Kam


Plant Goniothalamus fulvus Hk. f. Goniothalamus malayanus Hk. f. &Th. Goniothalamus ridleyi King

Goniothalamus rufus Miq. Goniothalamus subevenius King Goniothalamus suluensis Merr. Goniothalamus uvarioides King Meiogyne virgata (BI.) Miq. Mezzettia umbellata Becc. Miliusa longipes Mitrephora maingayii Monocarpia marginalis (Scheff.) J. Sinclair Oncodostigma monosperma J. Sinclair Orophea enterocarpa Maing Oxymitrafilipes Hk. f. Oxymitra kingii J. Sinclair Oxymitra latifolia Hk. f. Phaeanthus crassipetalus Becc.

Plant part

Alkaloid test

References

L B B

w m w

IU)

L L B S L,B S

s w m m s w

B B L L,B B B B,R B L B R B

s w w s m w s s s w s m

111] [11] [14]

B

s

[11]

L B B L B L B

m s s m s s s

[11]

[12] [5] [H] [9] [11] [10]

[11] [12] [12] [4] 15] [11] 14] [11]

[11] [11] [11,14] [11]


291


Plant Phaeanthus nutans Phaeanthus ophthalmicus (Roxb.) J. Sinclair Polyalthia affinis T. & B. Polyalthia cauliflora Hk. f.

Polyalthia cinnamomea Hk. f. & Th. Polyalthia clavigera King Polyalthia cunangiodes Polyalthia hookeriana Miq.

Polyalthia hypoleuca Hk. f. & Th. Polyalthia insignis (Hk. f.) Airy-Shaw

Polyalthia jenkensii Hk. f. et Th. Polyalthia macropoda Polyalthia microtus Miq. Polyalthia motleyana var. glabrescens Airy-Shaw Polyalthia rumphii (Bl.) Merr. Polyalthia stenopetala (Hk. f. & Th.) Ridley

Plant part

Alkaloid test

References

L,B L, S, F, R L,B R S L B S L B L L,B L L,B,R L,B L,B L,B,S

s s s s w w s m w s m w w s s m w

[4] [5] [4,11] [4] [10] [11,12]

L B L,B L B B L,B,R L B S,R L,B L

w s s m s w s w s s w w

[11]

L B

w s

[H]

[H] [12] [11] [14] [11] [15] [5] [11] [14] [12]

[12] [15] [14] [5] [11] [5] [11] [H]

292

T.-S. Kam


Plant Polyalthia tenuipes Merrill Popowia odoardoi Diels Popowia perakensis King Popowia pisocarpa (Bl.) Endl.

Popowia ramosissima Popowia tomentosa Maingay ex Hk. f. & Th. Pseuduvaria macrophylla (Oliv.) Merr. Pseuduvaria monticola J. Sinclair Trivalvaria macrophylla (Bl.) Miq. Trivalvaria pumila J. Sinclair Uvaria lobbiana Hk.f. & Th. Uvaria sorzogonensis Presl. Xylopia caudata Hk. f. & Th.

Plant part

Alkaloid test

References

L,B L B B B,R,Sd L,B L L,B,R Sd,R L B L B B B S,R L R B L,S L B L,S L,B

w w s m s s m s s m s w m m s s m s s w m w w w

nil

Xylopia ferruginea Hk. f. & Th. Xylopia fusca Maing ex. Hk. f. &Th. L,B Xylopia stenopetala Oliv. Apocynaceae L Aganosma marginata (Roxb.) G. Don L,S Allamanda catharica L. L Alstonia angustifolia var. latifolia L L L Alstonia angustifolia Wall

tin nil [5] [4,U] [15] [4] [5] [11] [11] [11] [11] [4] [11] [4] [11] [12] [12] [7] [12] [12]

w w s m w m

[12] [7] [16]

[12]

AlkaloidsfromMalaysian Flora

293


Plant Alstonia angustifolia Wall Alstonia angustiloba Miq. Alstonia macrophylla Wall, ex G. Don Alstonia spathulata Bl.

Alstonia undulifolia K. M. Koschummen et K.M. Wong Chilocarpus costatus Chilocarpus obtusifolius Merr. Chilocarpus vernicosus Bl. Chonemorpha penangensis Dyera costulata Hk. f. Dyera laxiflora Hk. f. Dyera polyphylla (Miq.) Ashton Ervatamia coronaria (Wild.) Stapf. Ervatamia cylindrocarpa (King and Gamble) Corner Ervatamia macrocarpa Hk.f. Ervatamia malaccensis Ervatamia peduncularis Wall. Ervatamia polyneura (Scort. ex King and Gamble) Corner Hunteria zeylanica (Retz.) Gardn.ex Thw. Kibatalia maingayi Hk. f. R. E. Wood Kopsia arborea Bl.

Plant part

Alkaloid test

B L L,B L,B L L,B L B B

s m s s + s w s m

[11] [10,12]

R L

s m

[4]

L,B L,S R L L,S L L B L

w s s w + w s w w

[11] [4] [5] [12]

L,B L,S,R L L B L,B

s s s m s s

[11] [5] [11] [11]

L, B, R, Fl L L

s w s

[5] [12]

References

[11] [12] [7,11] [3]

[4] [11]

[11]

[6] [12] [11] [11]

[11]

[11,18]

294

T.-S. Kfttn


Plant Kopsia arborea Bl. Kopsia dasyrachis Ridl. KopsiafruticosaA. DC

Kopsia griffithii King and Gamble Kopsia lapidilecta van der Sleesen Kopsia larutensis King and Gamble Kopsia macrophylla Hk. f. Kopsia mitrephora van der Sleesen Kopsia pauciflora Hk. f. Kopsia profunda Markgraf

Plant part

Alkaloid test

References

S L B L,B L S L,B

m m s s m s s

[18]

L,B L,B

s s

[11] [1U8]

s s s s m s s w s + w w s s w s m w s s +

[11] [11] [11,19] [18]

L,B L,B L,B L S L,B Kopsia sleeseniana Markgraf & Bl. L,B Kopsia singapurensis Ridl. L S S L Kopsia tenuis Leenh. & Steenis B L,B Kopsia teoi L. Allorge L, Sd, B, R Leuconotis eugenifolia L,B Leuconotis griffithii Hk. f. L,S,R B B Leuconotis maingayi Dyer L,S Lochnera rosea Reichb. R L L Melodinus orientalis BL

w

[11] [11] [8] [11]

[12] [11]

m [6] [12,19] [19] [19] [5] [20] [4] [11,12] [11] [4,7] [4] [3] [12]


295


Plant Rauvolfia perakensis King and Gamble Rhynchodia verrucosa Tabernaemontana coronaria Tabernaemontana corymbosa Roxb. Tabernaemontana macrocarpa Jack Tabernaemontana malaccensis Hk. f. Tabernaemontana pandacaqui Lam Tabernaemontana peduncularis Tabernaemontana sphaerocarpa BI. Voacanga havilandii Ridl. Araceae Amorphophailus campanulatus Araliaceae Aralia montana Bl. Polyscias cf.javanica K. & V. Scheffierajunghuniana (Miq.) Harms Aristolochiaceae Apama corymbosa Soler. Asclepiadaceae Asclepias curassavica Calotropis gigantea Ait. Dischidia rqfflesiana Wall.

Plant part

Alkaloid test

References

S

+

[6]

R L,S L L L F L,S,R B L

s s s w w m s s w

[5]

L,R L B L B

s m s m s

Sd

W ["] [12] [12] [4] [11] [12] [4] [12] [12]

[5]

F S S

w w w

[7] [10]

L,S L

w w

[7] [10]

L S L,S

+ + +

[3] [6] [6]

[9]

296

T.-S. Kam


Plant Bombacaceae Durio zibethinus Murr. Boraginaceae Heliotropium indicum Caesalpiniaceae Bauhinia purpurea L. Cassia spectabilis (cf. Corner) Saraca declinata (Jack) Miq. Campanulaceae Isotoma longiflora Presl. Laurentia longiflora (L.) Petermann Pratia begoniaefolia Lidl. Capparidaceae Capparis micracantha DC. Capparis scortechinii Cleome rutidosperma DC. Crataeva membranifolia Miq. Caricaceae Carica papaya Celastraceae Glyptopetalum quadrangulare Kurrimia paniculata Wall. Chloranthaceae Chloranthus brachystachys Bl. Clusiaceae Garcinia paTvifolia (Miq.) Miq. Compositae Adenostemma lavenia Ageratum conyzoides

Plant part

Alkaloid test

References

B, Wd, Sd

w

[7]

S

s

[4]

L,S L S S

w m w w

[10]

L,S,W L,F,R W

+ s s

[6] [4] [7]

W

w

[9J

L B L, B, Sd, R W B

w m s w w

[11]

L

+

[3]

L,B L

m s

[13] [8]

B

w

[11]

L,S

w

[7]

L L

+ +

[3] [3]

[8] [9]

[5] [8] [11]


297

Table 1. Alkaloid-positive plants from phytochemicai surveys (cont.)

Plant Blumea balsamifera Elephantopus tomentosus L. Erichtites valerianifolia Pluchea indica Synedrella nodiflora Vernonia arborea King Vernonia cineria Vernonia patula Connaraceae Cnestis palala var. palala Convolulaceae Erycibe stapfiana Jacquemontia tomentella Cornaceae Alangium unilcoulare King Aralidium pinnatifldum Miq. Mastixia cuspidata Cucurbitaceae Gymnopetalum integrifolium Trichosanthes wallichiana Trichosanthes wawraei Datiscaceae Octomeles sumatranum Miq. Dichapetalaceae Dichapetalum griffithii Dilleniaceae Tetracera scandens (L.) Merr Dioscoreaceae Dioscorea hispida Dioscorea scortechinii

Plant part

Alkaloid test

References

L W L L L L L L L

+

[31

w + + + w w + +

[7] [3] [3] [3]

R

s

[5]

F L

s +

[5] [3]

L S L L

w m w w

M [*] [16]

Sd R Sd

s s s

[5] [5] [5]

B

w

[H]

L,S,R

s

[5]

F

w

[7]

S,R B

s s

[4] [5]

[11] [17] [3] [3]

298

T.-S. Kam


Plant Dipterocarpaceae Dipterocarpus crinitus Dyer. Shorea curtisii Dyer ex King Shorea glauca King Shorea resina-negra Foxw. Ebenaceae Diospyros discolor Willd. Diospyros subrhomboidea Elaeocarpaceae Elaeocarpus brevipes Elaeocarpus petiolatus (Jack.) Wall. Elaeocarpus robustus Roxb. Ericaceae Lyonia ovalifolia (Wall.) Drude Rhododendron jasminiflorum Hk. Rhododendron stenophyllum Vaccinium dialypetalum J. J. S. Vaccinium laurifolium (Bl.) Miq. var. ellipticum (Bl.) Sleum. Vaccinium viocifolium K.&G. var. bicalcaratum Sleum. Escalloniaceae Polyosma laete-virens Griff. Euphorbiaceae Acalypha grandis Benth. var. longi-acuminata Hayata Acalypha indica L. Agrostistachys gaudichaudi Mull. Antidesma cuspidatum Muell.-Arg. Antidesma pendulum Hook. Antidesma salicinum Ridl.

ant part

Alkaloid test

Referer

S L,B L,S L,B

w w w w

[8] [7] [7] [7]

L,S S,F

+ s

[6] [4]

L L,S

+ w

[3] [7]

L, S

w

[7]

B L L S L

w w + w w

[11] [11] [3] [11] [11]

S

w

[11]

L

w

in]

-,s

w

[8]

W B W L

w m w w m w

[10]

s s

[11] [9] [8] [10]


299


Plant Aporosa arborea (Bl.) M. A. Aporosa symplocoides Baccaurea lanceolata Baccaurea motleyana Bridelia ovata Decne. Bridelia stipularis (L.) Bl. Bridelia fomentosa Bl. Claoxylon longifolium (Bl.) Endl. ex Hassk. Croton argyratum Bl. Crotonjoufra Roxb. Elateriospermum tapos Bl. Emblica officinalis Gaertn. Euphorbia atoto Forst. f. Flueggea virosa Baill. Gelonium glomerulatum Glochidion cf brunneum Glochidion leiostylum Kurz Glochidion sericeum (Bl.) Hk.f. Glochidion wallichianum Mull. Jatropha gossypifolia L. Macaranga curtisii Macaranga hullettii King (male) Macaranga triloba Muell.-Arg. Mailotus cf. floribunda Mull. Mallotus philippinensis Muell.-Arg. Melanolepis multiglandulosa (Bl.) Rchb. f. & Zoll. Microdesmis ceasarifolia Omalanthus populnea (Geisel.) Pax.

Plant part

Alkaloid test

References

L L L,B F F S L,S,F L

w m m s +

[10] [14]

L,S W L B L,S S L,S Sd L,B S L F S L L,S L S F L

B,R L,S

w w m w + w w + m s s m w w w m w w + +

[15] [4] [6] [9] [7] [12] [7] [6] [11] [11] [6] [7] [7] [5] [13] [10] [11] [7] [7] [17] [7] [3] [6]

w w

[8] [9]

w

[10]

s w

[5] [7]

300

T.-S. Kam


Plant Ostodes macrophylla Benth. Ptychopyxis caput-medusae Sapium baccatum Roxb. Fagaceae Castanopsis lucida Ficoidaceae Sesuvium portulacastrum (L.) L. Flacourtiaceae Casearia clarkei Homalium caryophyllaceum (Z. & M.) Benth. Flagellariaceae Flagellaria indica L. Geseriaceae Cyrtandromoea acuminata Bth. & Hk. Didymocarpus hispida Ridl. Gnetaceae Gnetum brunonianum Gnetum cuspidatum Bl. Gnetum latifolium Bl. Goodeniaceae Scaevola taccada (Gaertn.) Roxb. Gramineae Imperata cylindrica Hernandiaceae Hernandia ovigera L. Hippocrateaceae Salacia grandiflora Kurz Icacinaceae Gomphandra affinis

Plant part

Alkaloid test

References

L,S S B

w s s

[10]

L

w

[16]

W

m

[9]

S,Sd,R S

s w

[5] [9]

W

w

[7]

L S W

s w w

[9]

L L B L, B, S, R, Sd Wd

s w m s +

[5] [11]

L,S

s

[7]

L

+

[3]

L,S

w

[7]

L

w

[10]

L,B

s

[5]

[5] [11]

[9]

[5] [6]


301


Plant Gomphandra afflnis Gomphandra quadrifida (Bl.) Sleumer var. quadrifida Phytocrene bracteata Phytocrene oblonga Iridaceae Trimeza martinicensis (Jacq.) Herb. Labiatae Dysophylla auricularia Hyptis brevipis Ocimum basilicum L. Lauraceae Actinodaphne glomeratus Nees Actinodaphne montana Actinodaphne sesquipedalis Alseodaphne peduncularis Hk. f. Alseodaphne petiolare Beilschmiedia madang CassythafiliformisL. Cinnamomum iners Bl. Cinnamomum mollissimum Hk. f. Cinnamomum paraneuron Miq. Cinnamomum pubescens Ridl. Dehaasia caesia Dehaasia incrassata (Jack) Kostermans Eusideroxylon zwageri T. & B

Plant part

Alkaloid test

References

L,S,R L

s w

[4] [10]

F F

s s

[4] [4]

W

w

[7]

L L L,S L

+ +

[3] [3] [7] [10]

L,B B, F,R B,R L L,B L,S,R L, B, F, R L W B L B L,S B L B B L, F, S, R L,B

w w s s s s s s s w m s w s w s m s s s w

nu [5] [4,5] [4]

[HI [4] [4] [16] [7] [11] [17] [11] [7] [11] [15] [5,11,14] [5,14] [11]

302

T.-S. Kam


Plant Lindera cubeba (Lour.) Pers. Lindera lucida (Bl.) Boerl. Lindera oxyphylla Hk. f. Lindera pentantha K. & V. Lindera pipericarpa Boerl. Lindera pipericarpa Boerl. Lindera spathacea Lindera spathacea var. tomentosa Litsea amara Litsea elliptibacea Litsea oppostifolia L.S. Gibbs Litsea spathacea Litsea tomentosa Bl. Litsea trunciflora Gamble

Plant part

Alkaloid test

References

L,B L,S,F B R S L R R R R L B B F B L

s w w m w w s s s s m

[i>] [7] [7]

L,S S L S L S B,R L, B, R, Fl L,B,R L,S,R L,B,R F

w s w

Fl L L

+ + s

s s s s m

[9] [11,16] [4] [4]

14] [5] [15J [11] [5] [11] [8]

c

Litsea umbellata (Lour.) Merr. Neolitsea cassiaefolia (Bl.) Merr. Neolitsea zeylanica Merr. Nothophoebe pahangensis Notaphoebe panduriformis Gamble Phoebe macrophylla Phoebe opaca Phoebe taroyna Stemmatodaphne perakensis Leguminosae Andira surinamensis Splitg. Cassia siamea Centrosema pubescens

s m s s s s s s s

[10] [8] [7] [16] [7] [5] [5] [4]

14] [4,5] [4] [6] [3] [17]


303


Plant

Plant part

Alkaloid test

References

L

+

[3]

Crotalaria mucronata Desv.

W

w

Crotalaria

L

[11] [17]

L,F

s +

L

+

[3]

Crotalaria

anagyroides mucronata

Crotalaria striata DC.

[6]

Dialium platysepalum

Sd

s

[5]

Dracaena conferta

L

s

[4]

Enterolobium soman

L,S

s

[4]

Indigofera teysmanii

S

s

[4]

L,B,R

[6]

Millettia abiflora Mimosa sepiaria Benth.

B

s +

Pithecellobium dulce

L

+

[3]

Pithecellobium ellipticum

Sd

s

15]

Pithecellobium jiringa Prain

S

+

[6]

Pterocarpus indicus

L

s

[4]

Saraca declinata Miq.

B

w

[11]

Spatholobus gyrocarpus Bth.

B

[11]

Swartzia pinnata Willd.

S

m +

Sd

s

[5]

L

w

[7]

[5]

[6]

Liliaceae Dracaena congesta Liliaceae Roucheria griffithiana Planch.

S

s

Loganiaceae Fagraea blumei G. Don Fagraea crenulata Maing.

L

w

[11]

L,S,F

m

[7]

L,F

w

[7]

S

m

L

+

[3]

F

s

[7]

ex Clarke Fagraea fragrans Roxb.

Fagraea racemosa Jack. ex Wall. Gelsemium elegans Benth.

[6]

304

T.-S. Kim


Plant part

Alkaloid test

References

Strychnos ignatii Bergius Strychnos ovalifolia Lythraceae Sonneratia acida L. Magnoliaceae Magnolia maingayi Talauma betongensis Craib. Talauma obovata Korthals

L,B S,R

s s

[H]

L

w

[10]

L B L

w s w

[16] [11] [11]

Talauma singapurensis Talauma villosa Malvaceae Hibiscus mutabilis Sida rhombifolia L. Melastomataceae Allomorphia malaccensis Ridl. Amplectrum divaricatum Triana. Dissochaeta cf. sagittata Bl. Melastoma schizocarpa Ridl. Memecylon oleaefolium Pternandra echinata Jack. Meliaceae Aglaia leucophylla Carapa guianensis Aubl.

,B,R L

s w

[5] [16)

L W

+ m

[3] [7]

L,S F

w m

[7,17]

S S L L,S

w w s w

[8] [7] [5] [7]

L S,Sd Sd L S S,F S Sd W

s w + w w w w +

[15] [7] [61 [16]

Plant

Chisocheton ceramicus Dysoxylum cauliflorum Hiem Melia azedarach L. Payena obscura Burck. Swietinia macrophylla King Turraea cf breviflora Ridl.

w

[4]

[7]

[9] [7] [10] [6] [10]


305


Plant Menispermaceae Albertisia crassa Forman Albertisia papuana Becc. Arcangelisia flava (L.) Merr. Arcangelisia loureiri (Pierre) Diels Coscinium blumeanum Miers ex Hk. f. Coscinium wallichianum Miers

Cyclea laxiflora Miers

Fibraurea chloroleuca Miers

Fibraurea tinctoria Lour. Hypserpa cuspidata Limacia oblonga Miers

Pericampylus glaucus (Lmk) Merr. Tinomiscium petiolare Tinospora crispa (L.) Miers. ex Hk. f. & Thorns. Mimosaceae Acacia auriculiformis A. Cunn. Adenanthera pavonina L. Moraceae Ficus annulata Bl.

Plant part

Alkaloid test

References

L,S B S S L,R B

w s m s s s

[11] [11] [11] [4,10]

B, Sd, R L,S S S,R B W S,R B,R L S L L,S R B W L S,R S

s s + s s s s s + s +

[5] [4] [6] [5]

s s s w s s m

L,S

w

[8]

S

w

[7]

L,S,F

w

[7]

[4] [11]

[11] [4] [5] [4] [6] [11] [3] [5] [4,5] [11] [9] [5] [4,5] [7]

306

T.-S. Kam


Plant Ficus deltoidea Jack. Ficus fistulosa Ficus Julva Reinw. ex Bl. Ficus grossularioides Brum. f. Ficus hirta L. f. Ficus hispida L. Ficus indica L. Hullettia dumosa Myristicaceae Horsfleldia superba Warb. Knema communis J. Sinclair Myrsinaceae Ardisia colorata Roxb. Ardisia elliptica Thunb. Ardisia macrophylla Ardiceae serrata (Car.) Pers. Maesa impressinervia King Maesa ramentacea Wall. Myrtaceae Decaspermum fruticosum J. R. & G. Forst. Eugenia longiflora (Presl.) F. Vill. Nyctaginaceae Boerhavia diffusa L. Ochnaceae Gomphia serrata (Gaertn.) Kanis Olacaceae Lepionurus sylvestris Ochanostachys amentacea Mast. Strombosia multiflora King

Plant part

Alkaloid test

References

L,S,F L,B S L L L L L L

w w w w m m s m s

[7] [14]

L B L

s m s

[H]

L B B L L,B L B

w

[11]

s + m w m m

[6] [15] [11] [11] [7]

S S L,S

m w w

[8] [10] [7]

W

m

[11]

B

w

HI]

L,F L,S L

s w w

[5] [7]

[7] [10] [7] [11] [5] [8] [5] [11]

[U]


307


Plant Oleaceae Jasminum bifarium Linociera montana (Bl.) DC. Ligustrum sinense Lour. Olea brachiata (cf. Corner) Olea maritima Wall, ex DC. Osmanthus scortechinii King Oxalidaceae Averrhoa carambola L. Palmae Calamus javensis Plectocomiopsis geminiflorus

Plant part

Alkaloid test

References

L L,S L,B L,S S L,B

+

w m m w w

[3] [8]

[11]

w

[8]

s s s

[5] [5] [4,5]

m

[7]

w w w w w

[7]

w

l«]

L Sd F

Pandanaceae Pandanus recurvatus St. John Papilionaceae Dalbergia junghuhnii Benth. L,S Derris multiflora Benth. S Desmodium umbellatum (L.) DC. L,S Millettis decipiens Prain. L,S Moghania macrophylla (Willd.) O. K. F Passifloraceae W Passiflora foetida L. Passiflora laurifolia Passiflora quadrangularis L. Piperaceae Piper aduncum L. Piper magnibaccum C. DC. Piper porphyrophyllum Piper stylosum Miq. Polygalaceae Poly gala paniculata L.

L L W L,S L,S L,S,R

W

w

[>1] [10]

[9]

m

[7] [7] [7]

+ +

[3] 13]

m

[11]

w m s m

17] [10]

[4] [9] [7]

308

T.-S. Kam


Plant Salomonia cantoniensis Lour. Xanthophyllum excelsum (Bl) Miq. Xanthophyllum palembanicum Miq. Pontederaceae Eichornia crassipes Ranunculaceae Naravelia laurifolia Wall, ex Hook. f. Thorns. Rhamnaceae Gouania javanica Miq. Smythea lanceata (Tul.) Summerh. Rhizophoraceae Bruguiera cylindrica (L.) Bl. Carallia brachiata Pellacalyx axillaris Korth.

Pellacalyx saccardianus Scort. Rubiaceae Anthocephalus chinensis (Lamk.) Rich, ex Walp. Argostemma involucratum Hemsl. Aulacodiscuspremnoides Hk. f. Canthium didymum Cephaelis psychotrioides Valeton triceps Ridl. Chasalia chartaceae Craib Chasalia pubescens Ridl. Chasalia curviflora Thw.

Plant part

Alkaloid test

References

W F1,B L,S L, B, R, Fl L S

w s m s s m

[8] [5] [9] [5] [8]

L

+

[3]

US

w

[8]

S L

w w

[9,10] [9]

S L L 3

w w m

[7] [16]

L B S

W

[9]

s m

[>U

s w w w w s w w m w

[11]

L B W L L W L S L,B L,B

[11]

[7]

[7] [10] [17] [11] [8] [11] [11]


309


Plant Chonemorpha penangensis Ridl. Cqffea canephora Pierre ex Froehner var. robusta (Linden ex De Wildem.) Chevalier Coptosapelta flavescens Coptosapelta tomentosa (Bl.) Val. ex K. Heyne Gardenia carinata Wall. Hedyotis capitellata lxora brunonis Ixora coccinea L. Ixora congesta Roxb. Ixora nigricans Ixora pendula Jack Ixora sticta Roxb. Ixora umbellata Valet. Morinda citrifolia L. Morinda elliptica Ridl. Nauclea maingayi Ophiorrhiza communis Ridl. Ophiorrhiza discolor R. Br. Ophiorrhiza tomentosa Jack Oxyceros curtisii (King and Gamble) K. M. Wong Oxyceros penangianus (King and Gamble) D. D. Tirvengadum Pavetta graciliflora Wall.

Plant part

Alkaloid test

References

L,S L

s w

[7] [9]

R S

s w

[4] [9]

B S R S L L L L L L B L S L S,R W

+

[6] [101

w w w L

w s + w w m w w w w w m w s m s w m m

[4] [6] [14] [8] [ID [14] [11] [11] [11] [7] [11] [4] [11] [11] [7] [11] [11] [11]

L F S

s s s

[4,5,11] [4,5] [4]

310

T.-S. Kam


Plant

Plant part

L L,S L,B Pavetta pauciflora Ridl. L,S Petungafloribunda Ridl. Pleiocarpidia capituligera (Ridl.) Brem. L,S L Porterandia anisophylla L,B Psychotria montana Bl. >,S,R L,B Psychotria rostrata L Randia anisophylla Jack. S S Randia densiflora Benth. S L,S Randia macrantha DC. L Randia macrophylla Hook. fil. S S Randia scortechinii King R Randia stenopetala S Tarennafragrans (Bl.) K. & V. L Tarenna mollis (Wall, ex Hk. f.) S B. L. Robinson L Uncaria acida Roxb. L S L Uncaria borneensis Havil L Uncaria callophylla Korth S L S S Uncaria cordata (Lour.) Merr. B Uncaria cordata (Lour.) Merr. var. Pavetta indica L.

cordata

Alkaloid test

References

s w s w w w s s s w s w

[4,11] [8] [11] [10] [12] [16,17]

+ +

m w w s m w m s w m s s w m w m s

[11] [4] [13,17] [8] [10] [6] [6] [8] [9] [4] [9] [12] [5] [8] [12,17,21 [21] [12] [7] [11,17]


311


Plant Uncaria cordata Men. forma sundaica Ridsd. Uncaria elliptica R. Br. ex G. Don Uncaria ferrea (Bl.) DC. Uncaria gambir (Hunt.) Roxb.

Uncaria lanosa Wall var. ferrea Ridsd. Uncaria longiflora var pteropoda (Miq.) Ridsd Uncaria ovalifolia Roxb. Uncaria parviflora Uncaria pteropoda Miq.

Uncaria roxburghiana Korth. Uncaria sclerophylla Roxb. Uncaria umbellatum Urophyllum macrophyllum Korth. Urophyllum trifurcum Pears. Urophyllum umbellatum Miq. Rutaceae Acronychia laurifolia Bl. Acronychia porteri Atalantia kwangtungensis Atalantia roxburghiana Euodia glabra Euodia latifolia DC.

Plant part

Alkaloid test

References

L B L L,S L,S S,R L B L

m w w w s s m w w

["]

L

s

[12,21]

S L,S,R L,B L,S R R, S, Sd S L L L B L,S

m s s s s +

[7] [4] [5,7] [4] [4,5]

L,B L S B L S S L

w w m s w m w s

m m s w w w

[12,21] [8] [7] [4] [12] [11]

[6] [9] [7] [4] [9] [11] [12] [11] [22] [5] [22] [22] [U,23]

312

T.-S. Kam


Plant Euodia latifolia DC.

Euodia pilulifera King Glycosmis calcicola Glycosmis malayana Glycosmis pentaphylla Correa Glycosmis sapindoides Merrillia caloxylon Micromelum minutum (Forster F.) W. & A. Micromelum pubescens Muraya paniculata Jack Paramignya lobata Tetractomia tetrandra Craib. Triphasic* trifolia Xanthoxylum hirtellum Zanthoxylum myriacanthum Wall. Sapindaceae Allophylus cobbe Harpullia arborea Radik. Nephelium glabrum Sapotaceae Achras Sapota Linn. Madhuca korthalsii var. Lanceolata Madhuca mindanaensis Merr. Palaquium ridleyi King Scrophulariaceae Cyrtandromea acuminata

Plant part

Alkaloid test

B S R L,F B B R L,S L,R L,F1 S L S L,B L,B S B S L B,R S,B

w m s m w w s + s s m w m s + w m w w s w

References

[7] [4] [11,23] [22] [4] [6] [4] [22] [9] [5] [6] [22] [11] [22] [22] [5] [9,22]

L L,B Sd

m w s

[17]

S Sd B S

+

[6] [5]

s w w

[11] [5]

[HJ [7] [15]


313


Plant

Plant part

Alkaloid test

References

Simarubaceae L

+

[3]

S,R

s

[4]

Brugmansia suaveolens (Humb.

W

m

[H]

and Bonpl. ex Wild.) Bercht and Presl

S

w

[9]

Capsicum frutescens

L

+

[3]

Datura mete!

L

+

[3]

Lycium Chinese Mill.

S

+

[6]

Brucea javanica Eurycoma apiculata Solanaceae

Solatium blumei

L

s

[5]

Solatium ferox L.

W

w

[11]

Solarium nigrum

L

+

[3]

L, B, F L,S,F

w +

[11] [6]

L

w

[8]

R

s

[4]

L

w

[16]

L,B

s

[13]

L,R

m

[14]

Byttneria maingayi Mast.

S

m

[10]

Commersonia barlramia (L.)

L

w

[7]

Me lochia corchorifolia L.

W

w

[9]

Pterospermum cf. elongatum

L

w

[8]

S

w

[9]

Symplocos anomala Brand

L,B

m

[H]

Symplocos fasciculata Zoll.

L

w

[11]

Symplocos ophirensis Clarke

B

w

[11]

Solanum torvum Sw. Solanum verboseifolium L. Staphyleaceae Turpinia ovalifolia Stemonaceae Stichoneuion caudatum Sterculiaceae

Merr.

Korth. Sterculia parviflora Roxb. Symplocaceae

314

T.-S. Kam


Plant Taccaceae Tacca pinnatifida Forst. Taxaceae Podocarpus teysmanni Miq. Ternstroemiaceae Eurya acuminata DC. Ploiarium alternifolium Tiliaceae Grewia tomentosa Juss. Triumfetta rhomboidea Jacq. Ulmaceae Gironniera nervosa Trema cannabina Lour. Gironniera subaequalis Urticaceae Villebrunea silvatica Bl. Verbenaceae Avicennia alba Bl. Clerodendron deflexum Wall Clerodendron deflexum Wall Clerodendron disparifolium Bl. Clerodendron indicum (L.) O. K. Clerodendron inerme Benth. Clerodendron inerme (L.) Gaertn. Clerodendron japonicum (Thunb.) Sweet. Clerodendron laevifolium Bl. Clerodendron laurifolium Clerodendron myrmecophilum Ridl.

Plant part

Alkaloid test

References

F

w

[7]

L

m

[7]

L L

w +

[8] [3]

L S L,S

w +

[8] [6]

w

17]

L,B US R

w w s

[13] [7] [5]

L,B

w

["]

S L W L W L,B L

+

[6]

w s w m w w

[11] [H] [11] [10]

L,S

w

[7]

S L W

+ s w

[6] [17] [9]

[11] [10]

Alkaloids from Malaysian Mora

315


Plant Clerodendron serratum (L.) Moon. Clerodundron wallichii Merr. Duranta erecta L. Gmelina arborea L. Gmelina elliptica J. E. Smith Premna tomentosa Willd. Sphenodesma barbata Schauer Stachytarpheta indica Vahl.

Stachytarpheta jamaicensis (L.) Vahl. Stachytarpheta mutabilis (Jacq.) Vahl. Verbena bonariensis L. Vitex negundo L. Vitex ovata Thunb. Vitex pubescens Vitaceae Cayratia geniculata (Bl.) Gagn. Tetrastigma hookeri (Laws.) Planch. Zingiberaceae Globba pendula Roxb.

Plant part

Alkaloid test

References

L S S

s w w

[7]

L B,F L L,S L L,S W L

w w w w w m w +

[9] [7]

L,S

s

[7]

L

m

[7]

W L L,F L

w w w +

[H]

L

w

[9]

S

w

[9]

B

w

[11]

[9]

[8] [7]

["J [7] [11]

P]

[8] [7] [3]

316

T.-S. Kam

U . STRUCTURE ELUCIDATION AND CHEMISTRY

1.3.1. Isoquinoline and Related Alkaloids Isoquinoline and isoquinoline derived alkaloids are mainly distributed in the families Annonaceae, Lauraceae and Menispermaceae. Simple isoquinolines and derivatives. Ancistrocladus is the only genus of the Ancistrocladaceae and comprises some twenty species of lianas and shrubs found in the tropical rain forest of Asia and Africa. Examination of the bark extract of Ancistrocladus tectorius (Ancistrocladaceae) collected in Johore, Peninsular Malaysia, resulted in the isolation of a new simple isoquinoline, 6,8-dimethoxy-3hydroxymethyl-1-methylisoquinoline (1) and a new naphthylisoquinoline derivative, 4'-0demethylancistrocladine (4), together with the known isoquinolines, 6,8-dimethoxy-l,3dimethylisoquinoline (2) and (5)-6,8-dimethoxy-l,3-dimethyl-3,4-dihydroisoquinoline (3) [24J. Compound 1 was the major alkaloid present and compounds 2 and 3 were previously unknown as natural products. The related naphthylisoquinoline alkaloids ancistrocladine (5) and its atropisomer hamatine (6) were previously known from other Asian Ancistrocladus species [25] while the 7,3'-linked naphthyl-isoquinoline, ancistrotectorine (8), has been previously isolated from Ancistrocladus tectorius from Thailand [26]. The structure of 1 was deduced from spectral data (UV, MS, NMR) as well as by its ready conversion to the known 2 through successive mesylation and UAIH4 reduction. Likewise the structure and relative stereochemistry of 4 were established by spectral analysis (HMBC, NOESY) and by conversion to the known (-)-N-formyl-O-methylancistrocladine derivative 7 via successive formylation followed by methylation (Mel, NaH-DMF). Aporphines, Bisaporphines, Berberines, Azafluorenes, Aristolactams, seco-Benzyltetrahydroisoquinolines and Bisbenzylisoquinolines. The aporphine alkaloids constitute a large subgroup of alkaloids derived from isoquinoline and are widely distributed especially in the Annonaceae, Lauraceae, Magnoliaceae and Menispermaceae. Several new aporphine and berberine alkaloids which were uncovered in the period of the last ten years or so are from plants of the Annonaceae such as the 7-hydroxyaporphine, dasymachaline (9) from Desmos dasymachalus [27], the dioxoaporphine, 1,2,3-trimethoxy-4,5dioxo-6a,7-dehydroaporphine (10) from Pseuduvaria macrophylla [28], the tetrasubstituted

317

Alkaloids from Malaysian Flora Me

MeO

MeCX

OMe

OMe

Me

1

R = CH2OH

2

R = Me )Me

OMe

OR1

Me OMe

Me

4

R 1 = R 2 = R3 = H, V-S

5

R1 = Me, R2 = R3 = H, V-S

6

R1 = Me, R2 = R3 = H, V-fl

7

R1 = Me, R2 = Me, R3 = CHO, V-S

NMe

OMe 9

Me

10

318

T.-S. Kam MeO

MeOv

JV

MeO"

MeO' OH 11

14

OH MeO< MeO MeO H* .OMe

"OH 12

13 MeO.

MeO

OMe

OMe 15

319


17 R 1 =R2 =

H

18 R 1 = R 2 = Ac

19 R 1 = R 2 = H 20 R1 = R2 = Ac

aporphine, norisocorytuberine (11) from Trivalvaria macrophylla [29], the catecholic berberine, artavenustine (12) from Artabotrys venustus [30] and the tetrahydroprotoberberine, (-)-thaipetaline (13) from Polyalthia stenopetala [31]. In addition, the aporphine-derived phenanthrenoid, l-(N-acetyl-N-methylamino)ethyl-3,4,6-trimethoxy-7-hydroxyphenanthrene (14), was isolated from Aromadendron elegans of the Magnoliaceae family [32]. Trivalvaria macrophylla also furnished in addition to the known bisaporphine, N-methylurabaine (15), the new but related bisaporphine, trivalvone (16) [29].

320

T.-S. Kam

Examination of the stem-bark extract of Orophea enterocarpa led to the isolation of two new aristolactams, viz., enterocarpam-I (17) and enterocarpam-II (19), accompanied by the known enterocarpam-I acetate (18) and enterocarpam-II acetate (20) [33]. Two new azafluorene alkaloids kinabaline (21) and oncodine (22) were obtained from the annonaceous plants Meiogyne virgata and Oncodostigma monospermy respectively [34,35].

MeO,

MeO

21

22

MeO.

"TO

MeO

MeO

NMe

, ^R

OMe

MeO

23 R = H 24 R = OMe

Recently two jeco-benzyltetrahydroisoquinolines, polysignine (23) and methoxypolysignine (24), were obtained from Polyalthia insignis in addition to (-)-asimilobine, oxostephanine, O-methylmoschatoline and liriodenine [36]. The 'H NMR of polysignine showed two proton singlets at 6 6.67 and 6.58 due to the isolated H(2) and H(5) and another set of two 2H-doublets at 8 6.82 and 7.07 (J 8.8 Hz) due to H(2'), H(6') and H(3'), H(5') respectively. The aliphatic H(ot) and H(P) signals were observed


321

as multiplets centered at 8 2.44 and 2.71, respectively, while the H(a') and H(P') signals were overlapped as a broad singlet at 5 2.81. A possible pathway from a benzyltetrahydroisoquinoline precursor (25) was suggested involving N-methylation followed by either reductive cleavage of the C(\)-N bond or by stepwise P-elimination and reduction steps.

1 2 26 R = Me, R = H 1 2 27 R = H, R = Me

29 The bark of Phoebe grandis (Lauraceae) gave the known aporphines, boldine, norboldine, laurotetanine and lindecarpine while the leaves yielded two new alkaloids, phoebegrandines A (26) and B (27) [37], which belong to the rare proaporphine-tryptamine group of compounds exemplified by roehybridine (28) (syn series) and roemeridine (29) (anti series)fromRoemeria hybrida [38,39]. The structure of 29 was previously established by X-ray analysis [40].

T.-S. Kam

322

30

31

32

MeN

33


323

Four new bisbenzylisoquinolines, viz., (-)-2,2'-bisnorphaeanthine (30), (+)-pangkoramine (31), (+)-pangkorimine (32) and (+)-nor-2'-cocsuline (33), in addition to the known bisbenzylisoquinolines, (+)-lindoldhamine, (+)-daphnoline, (+)-dapnandrine, (+)-bisnoraromoline, (+)cocsuline, (+)-cocsoline, (+)-Omethyl cocsoline and (+)-apateline were obtained from the Menispermaceous plant Albertisia cf. A. papuana [41]. The Thai members of the Menispermaceae, especially from the genera Cyclea and Stephania, have received attention and were found to provide many bisbenzylisoquinoline alkaloids [42].

MeO

MeO

34

35

Hasubanan alkaloids The hasubanan alkaloids are a small group of about 30 compounds found mainly in Stephania species [43]. Two new alkaloids belonging to this class, (+)-clolimalongine (34) and (+)-limalongine (35) were isolated from the bark of Limacia oblonga (Menispermaceae) in addition to the known alkaloids (+)-stepharine (a proaporphine) and four aporphines, lysicamine, homomoschatoline, imenine and splendidine [44]. The two alkaloids 34 and 35 are structurally similar, the only difference being the presence of a chlorine atom in clolimalongine (34) as indicated by the mass-spectral data. These alkaloids are closely related to (-)-acutumine and (-)-acutumidine, two other chlorine containing compounds previously isolated from another Menispermaceous plant. The structure of clolimalongine is similar to that of acutumidine differing only by the absence of the alcoholic function and the presence of the methoxyl group at C(3) instead of at C(2) in clolimalongine, and this is reflected in the similarity of the spectral data of both compounds. The structure and absolute configuration of (-)-acutumidine have been previously determined by X-ray analysis.

324

T.-S. Kam

In the case of clolimalongine, the relative configuration at C(10) and the spiro carbon C(l I) were deduced from NOE experiments in which irradiation of the H(l) (methylene) signal resulted in enhancement of H(10) (geminal to chlorine) and vice versa, showing that the C(l) methylenes and the geminal H(10) are on the same side with respect to each other. The spectral data of (+)-limalongine (35) are in agreement with a structure in which the C(10) chlorine atom of clolimalongine has been replaced by hydrogen.

1.3.2. Steroidal alkaloids Steroidal alkaloids have been encountered only in one Malaysian species, viz., Holarrhena curtisii, from which holacurtine (36), the first aminoglycosteroid was obtained [45]. Previous studies of African and Indian Holarrhena showed that these plants provided mainly steroidal alkaloids of the aminopregnane-type [46-48]. The Indian species H. antidysenterica in particular has received considerable attention since the plant has a long history of being used in the treatment of dysentery [49,50]. A second study of the Malaysian H. curtisii was prompted by the observation that the chloroform and ethanol extracts of the leaves showed significant leishmanicidal activity which was subsequently traced to the basic fraction derived from these extracts. Further fractionation led to the isolation of several aminoglycosteroids, holacurtine (36), Af-demethylholacurtine (37), 17-e/?/-hoIacurtine (38), 17-e/?/-jV-demethylholacurtine (39), holacurtinol (40) and aminopregnanes, holamine (41), 3ot-amino-14P-hydroxypregnan-20-one (42) and 15oc-hydroxyholamine (43). Of these, compounds 38, 39, 40, 42 and 43 were new natural products [51]. The aminoglycosteroids 36 - 40, showed typical mass-spectra with the pregnane aglycone fragment invariably detected as the base peak, while the D-cymaropyranose sugar unit was readily identified from the l3C NMR spectra. The C(17) epimers of the known holacurtine and Af-demethylholacurtine, 38 and 39, respectively, showed changes in the 'H NMR spectra with respect to the H(17) signal. In holacurtine and N-demethylholacurtine, the H(17) signal appeared as a doublet of doublets at 5 2.9 with J 9 and 4.5 Hz indicative of an a-stereochemistry for H( 17) which has also been observed for other pregnane glucosides, whereas in compounds 38 and 39, the H(17) signal appeared as a triplet at 8 3.25 with J 9 Hz. Further confirmation of the change in stereochemistry at C(17) for 38 and 39 were provided by NOE experiments in which irradiation of the H(17) signal caused enhancement of the C(18) methyl signal and vice-versa. Holacurtinol (40) is a minor alkaloid. The mass-spectrum showed fragments attributable to successive losses of two molecules of H2O suggesting the presence of two hydroxyl groups. The NMR spectral data showed the presence of the same sugar unit (4-deoxy-4-amino-P-Dcymaropyranose) as in 37 and 39, while the pregnane aglycone portion was similar to that of

325


holamine (41), in which a C(5)-C(6) double bond is present. Comparison of the NMR spectra of holacurtinol with the aminopregnanes 41 and 42 indicated that the site of hydroxylation was in the five-membered ring of the aglycone moiety. In addition to the C(14) P-hydroxyl function M

18

V

M e

M 7 N

H H

14

is]

36 37 38 39

OH

H

H

OH

R1 R1 R1 R1

= Me, R2 = a-H = H, R2 = a-H = Me, R2 = p-H = H, R2 = p-H

OH HM*

42

40

41 43

R=H R = OH

Hoisr

(8 85), the presence of an adjacent hydroxyl substituent was indicated by a low-field oxymethine resonance at 5 82 while the COSY and HMQC data revealed the presence of a CH-CH2-CH-OH fragment corresponding to C(17)-C(16)-C(15). The stereochemistry of the

326

T.-S. Kam

C(15) hydroxyl function was deduced to be a from the observed NOE interaction between the H(15) oxymethine and the C(18) methyl. The mass-spectrum of the aminosteroid 42 showed the presence of a fragment ion due to loss of H 2 0 while the base peak at m/z 56 due to the fragment CH2=CHCH=NH2+ provided confirmation for the amino function at C(3). The ! H and ,3C NMR spectral data showed signals characteristic of a C2|-pregnane skeleton with an amino group at C(3), a P-acetyl group at C(17), and a (J-OH substituent on the quaternary centre at C(14). The a-orientation of the amino group was determined from consideration of the H(3) and C(3) signals [52]. Compound 43 had NMR spectral data which were similar to holamine but differed in the signals due to H(15) and C(15) which have undergone significant downfield shifts compared to holamine (41). The location of the hydroxyl function was supported by the 2-D NMR data and the observed NOE interaction between H(15) and the C(18) methyl indicated that the stereochemistry of the 15-hydroxy is a. These steroidal alkaloids also showed cytotoxic activity (vide infra).

1.3.3. Monoterpene alkaloids The monoterpene alkaloids constitute a relatively small group of compounds and their occurrence has been restricted to several species of the genus Kopsia, viz., K. pauciflora, K. macrophylla and K. dasyrachis, from which several new monoterpene alkaloids related to skytanthine have been recently isolated. The North Borneo species Kopsia pauciflora provided five such monoterpene alkaloids, viz., kinabalurines A - F which are hydroxyskytanthine derivatives [53,54]. The first alkaloid isolated was kinabalurine A (44), which was obtained as colorless plates. The mass spectrum showed a molecular ion at m/z 183 (CnH2jNO) accompanied by fragments due to loss of H, Me and OH, and other fragments at m/z 84, 58 and 44 characteristic of skytanthine-type alkaloids. The IR spectrum indicated the presence of a hydroxyl group (3357 cm"1) and this was supported by the presence of an OH absorption ca. 8 3.27 in *H NMR. The ,3C NMR spectrum accounted for all eleven carbon atoms and the presence of an oxymethine was confirmed by the resonance at 8 80.0. Other significant peaks in ! H NMR included a pair of 3-proton doublets at 8 0.97 and 1.06 corresponding to two CH3CH- groups and an Af-methyl singlet at 8 2.25. The spectral data thus suggested that kinabalurine A is a hydroxyskytanthine derivative and COSY and HETCOR experiments confirmed that hydroxy substitution is at C(7) and allowed the full assignments of the NMR spectral data. In addition the observed J\.9 value of 10 Hz required a trans ring junction. The NMR data however were insufficient to establish the stereochemistry completely and unequivocally and for this purpose X-ray diffraction analysis was undertaken which established the structure of kinabalurine A. Kinabalurine A was the second 7-hydroxyskytanthine reported, the first being incarvilline (50)


327

isolated from the Chinese plant Incarvillea sinensis. The structure of incarvilline was also established by X-ray analysis [55]. Kinabalurine A differs from incarvilline in having a transring junction, a 7-p-OH substituent and a 4-oc-methyl group. Kinabalurine B (45) is the 7-oxo derivative of kinabalurine A as shown by the spectral data as well by its ready formation via oxidation of kinabalurine A. Similarly kinabalurine C (46) was readily shown to be the Ndemethyl derivative of kinabalurine B from the spectral data (loss of the Af-methyl signal in 'H and ,3C NMR and the presence of a secondary amine absorption in IR, 3400 cm"1). The transring junction in kinabalurine C was clearly shown in the 600 MHz l H NMR spectrum which showed the H(9) signal as a quartet of doublets (^5p-9a - «/|p-9a = ^8p-9a = 12 Hz, J\a-9a = 4 Hz).

«Me

Ma,

Me,,,

44

45 R 46 R

Me H

47

OH ,.Me

Ma,

"*'H

48

49

50

The spectral data for kinabalurine D (47) showed it to be yet another 7-hydroxyskytanthine diastereomer but proved inadequate for definitive assignment of stereochemistry. To this end kinabalurine D was converted to the quaternary ammonium iodide salt which provided suitable crystals for X-ray analysis. Kinabalurine D differs from kinabalurines A - C in having a 4-p-methyl group and a trans ring junction in which the stereochemistry of H(5)

328

T.-S. Kam

and H(9) are now reversed. Kinabalurine E (48) is the 7-oxo derivative of kinabalurine D as shown by the spectral data and by chemical correlation (PCC oxidation) with 47. Kinabalurine F (49) was obtained in minute amounts and its structure elucidation relied mainly on analysis of the 600 MHz NMR data and by comparison with 44, 47 and incarvilline (50). The 7-hydroxy group of kinabalurine F was deduced to be (3 based on comparison of the observed C(7) shift (8 81) with those of 44 (5 80) and 47 (5 81) which also have 7-P-OH. The C(7) shift in incarvilline which has a 7-a-OH is shifted upfield to about 5 73. The observed NOE interaction from H(7oc) to 8-methyl and from H(6a) to H(5) fixed their respective stereochemistry. Likewise the observed H(lp)/H(8p) NOE interaction allowed the assignment of H(lot) which appeared as a triplet with J 10.5 Hz requiring H(9) and H(la) to be transdiaxial which is possible only if H(9) is p. The observed H(3) signals as a triplet with J 11 Hz and a doublet of doublets (J 11, 2 Hz) are only consistent with H(4p), resulting in H(4P) and H(3a) being /ra/w-diaxial to each other. The 4-methyl of kinabalurine F therefore has astereochemistry. The kinabalurines together with incarvilline provide a useful array of stereoisomers in this series with various ring junction, 7-hydroxy and 4- and 8-methyl group stereochemistry.

Me,

SCHEME 1


329

Kopsia macrophylla provided two more new monoterpene alkaloids, kopsilactone (51) and kopsone (52), in addition to the known compounds 5,22-dioxokopsane, dregamine, akuammiline, tabernaemontanine, deacetylakuammiline, norpleiomutine and kopsoffme [56]. The IR spectrum of kopsilactone indicated the presence of a ylactone unit (1770 cm"1) which was supported by the observation of a quaternary carbon resonance at 5 176. The observed J^ value of 11 Hz required a /ra/w-diaxial arrangement between H(3a) and H(4P), while the estimated J4.5 value of ca. 4 Hz suggested a c/s-relationship between H(4) and H(5). An equatorial H(5) requires a cis ring junction between the piperidine and the flve-membered ring which in turn fixes the stereochemistry of the lactone-piperidine ring junction. The second monoterpene alkaloid kopsone gave a molecular ion which analysed for C,,H,9NO. The IR (1720 cm'1) and ,3C NMR (8 218) spectral data indicated the presence of a ketone function. Other groups indicated by the NMR spectra were two CHMe groups, an Nmethyl, three methylenes (one deshielded at 8 56) and four methines (one deshielded at 8 72). These, as well as a postulated common origin of 51 and 52 from the hypothetical 9-hydroxyskytanthine precursor 53 (Scheme 1), led to the proposed structure for kopsone. The relative stereochemistry was deduced from analysis of the 'H NMR spectrum. The leaves of K. dasyrachis gave kopsirachine (54), which is constituted from union of the flavonoid, catechine and two units of skytanthine. The gross structure was deduced from spectral and chemical evidence but the stereochemistry of the skytanthine units in 54 remains to be firmly established [57].

54 1.3.4. Indole alkaloids The monoterpenoid indole alkaloids constitute a large group and careful investigation of plants, particularly from the Apocynaceae (Kopsia, Tabernaemontana, Alstonia, Leuconotis) and Rubiaceae (Uncaria, Mitragyna) have yielded many novel compounds.

330

T.-S. Kam

Simple indole and oxindole alkaloids and tryptamine oligomers The simple P-carboline compound harmane (55), although widely distributed in several families is rarely encountered in the Apocynaceae. It has been recently obtained for the first time from Kopsia from K. grifflthii [58]. A new P-carboline, harmicine (2,3,5,6,11,11bhexahydro-lH-indolizino[8,7-b] indole) (56), which has been previously synthesized in racemic form was also isolated for the first time as an opticatly active natural product from Kopsia grifflthii [58]. The observation of Wenkert-Bohlmann bands in the IR spectrum (2780 and 2835 cm"1) suggested that the stereochemistry of H(l lb) is a and also that the C/D ring junction is trans. Further confirmation of the trans-ring junction was obtained from NOE experiments. Thus irradiation of the H(l lb) signal at 5 4.26 resulted in NOE enhancements of NH (8 8.19), H(la) (8 2.29), H(2a) (8 1.91), H(3a) (8 2.92), and H(5ct) (8 3.09). Likewise, irradiation of the NH signal caused enhancement of the H(Ub) signal and vice versa. The observed NOE interaction between H(l lb) with H(3a) as well as H(5a) confirmed the trans-C/D ring junction of harmicine. A new simple oxindole alkaloid, (-)-horsfiline (57) was obtained from Horsfieldia superba (Myristicaceae), in addition to the known alkaloids 6-methoxy-2-methyl-l,2,3,4-tetrahydro-pcarboline (58) and 5-methoxy-N,Af-dimethyltryptamine [59]. Horsfiline is a simple spiropyrrolidinyloxindole, its structure was deduced from spectral data (MS & NMR) as well as by partial synthesis from 58 via oxidation with Pb(OAc)4 to the acetoxyindolenine 59, followed by acid catalysed rearrangement (MeOH/AcOH) to (±)-horsfiline (Scheme 2) [59].

56

55 NMe

Me

57

58


331

Pb(OAc)4

MeOH-AcOH •*

58

57

59 SCHEME 2

CO

*Et

steps

NH2.HCI

60

R = PhCH2OCO SEM = Me3SiCH2CH2OCH2 61

ii - iv

Reagents: i. Bu3SnH, AIBN, PhMe, A; ii, Bu4NF, (DMF)-H2NCH2CH2NH2, 80 °C; Hi, cyclohexa-1,4-diene, Pd-C. EtOH; iv, HC0 2 H, HCHO, A

SCHEME 3

332

T.-S. Kam

A synthesis of horsfiline has been achieved based on intramolecular cyclization of an aryl radical as the key step as shown in Scheme 3 [60]. Protection of the amide nitrogen in the unsaturated bromoamide precursor 61 (obtained in several steps from ethyl glycine hydrochloride 60) proved to be necessary in order to achieve a suitable conformation for effective cyclization; reaction (Bu3SnH) of the unprotected amide precursor led only to reduction. Furthermore, introduction of an SEM protecting group was found to give a favourable ratio of 5-exo to 6-endo cyclization. The remaining steps involved removal of the various protecting groups followed by Eschweiler-Clarke /V-methylation to give racemic horsfiline. Me N

f-BuOCI

62

57

NaOH, MeOH-H20 70 °C

SCHEME 4

NHCH3

63 57

Reagents: i, DMSO (3 eq.), 37% HCI (3 eq.), 80 °C; ii, (CH2Q)n (1.2 eq.), AcOH, A

SCHEME 5

333


65

66

(*M-)-57 Reagents: i, NBS, AcOH, THF-H20, -15 °C; ii, TMSCI, MeOH, A; iii, 36 % aq. CH 2 0 (1.5 eq.) NaBH3CN, AcOH; MeOH-2N HCI (5:1), A; iv, NH3, MeOH; (CF3CO)20, dioxane, pyridine; v, NaBH4, EtOH, pyridine, 12 h. 40 °C

SCHEME 6 This was followed by two other alternative syntheses of racemic horsfiline, one based on an oxidative rearrangement of the tetrahydro-y-carboline derivative 62 (Scheme 4) and another involving a spirocyclization between the 2-oxo-5-methoxytryptamine derivative 63 and formaldehyde (Scheme 5) [61].

334

T.-S. Kam /0 2 Me

XX)H Me< NH2.HCI N H

BOC

64

65

BOC = C(=0)OCMe 3

A recent synthesis of /?-(-)-horsfiline (57) has been reported starting from the commercially available (5)-5-hydroxytryptophan (Scheme 6) [62]. The key step involved a crucial diastereoselective oxidation-rearrangement sequence to the desired oxindole 66 from an optically pure tetrahydro-P-carboline compound 65, readily obtained from (S)-5hydroxytryptophan hydrochloride (64).

-Me K 1

N H

A

(CH 2 0) n , PhMe, A O R1 = COO-(-)-Menthyl

R = (-)-Menthyl (E)

69

67

-Me i. ii

Reagents: i, powdered KOH, 18-crown-6 (cat), THF; Dowex 50Wx8; ii, DCC, DMAP, 2-mercapto-pyridine N-oxide, CH 2 CI 2 ; Bu 3 SnH, AIBN, PhH, A

SCHEME 7


335

A non-biomimetic synthesis of rt-(-)-horsfiline (57) has also been recently reported which was based on a thermal intermolecular 1,3-dipolar cycloaddition reaction as outlined in Scheme 7 [63]. The reaction of the optically active menthyl ester 67 acting as a dipolarophile, with the JV-methylazomethine ylide 68 (thermally generated in situ from sarcosine and formaldehyde) proceeded with ft-facial diastereoselectivity to produce a chromatographically separable mixture of 69 and the unwanted diastereomer. Subsequent cleavage of the chiral auxiliary, followed by removal of the carboxylic acid group by the Barton radical method provided /?-(-)horsfiline. The calicanthine-type alkaloids as represented by calicanthine, the isomeric chimonanthine (70) and the dehydro derivative isocalycanthine (71) have been previously known from various genera of the Celastraceae, including Bhesa. The bark extract of the Malaysian species, Bhesa paniculata provided two new members of this group which are related to the previously known isocalycanthine (71) [64], viz., bhesine (72) and dehydrobhesine (73), bhesine being the iV-8a' dehydro derivative of isocalycanthine. The structure and relative configuration of bhesine were established by X-ray diffraction analysis [65].

Me 70

71

Me 72

Me 73

336

T.-S. Kam

The major alkaloidal component of Psychotria rostrata Bl., a common undergrowth tree shrub was the known tetrameric alkaloid, quadrigemine B, accompanied by four other minor alkaloids, hodgkinsine, (-)-calycanthine, (+)-chimonanthine and calycosidine [66]. The isolation of (+)-chimonanthine is noteworthy since previous isolations were of the levorotatory or meso isomers and the (+)-enantiomer has been previously obtained only from the skin of the Columbian dart frog [67]. Heteroyohimbines, yohimbines and related oxindoies Plants of the genus Uncaria (Rubiaceae), comprising some 34 species, are distributed mainly in tropical and subtropical Asia, Africa and tropical America. Of these about 14 species occur in Peninsular Malaysia. Early studies in the sixties by Chan yielded the pentacyclic oxindole alkaloids isopteropodine (74) and pteropodine (75) from Uncaria pteropoda [68-71].

75 Phillipson et al have also carried out an extensive survey of the alkaloidal content of this genus based on investigations of herbarium samples using TLC and GCMS [72]. Plants of this genus provide mainly heteroyohimbines, oxindoies and yohimbines. Chemical studies of several species from Thailand such as U. attenuata, U. canescans, U. elliptica, U. homomalla and V. macropylla have also been carried out by Phillipson and others [73-78]. A chemotaxonomic

337


study of the Malaysian members of this genus has been recently carried out and this complements the studies of the Thai plants [79].

76

78 R = H 79 R = OH

77

80 R = a-OH 81 R s P-OH

Two new tetracyclic heteroyohimbines, isogambirine (76) and gambireine (77), in addition to three new dimers (callophylline, callopylline A, callophylline B, vide infra) and the known alkaloids dihydrocorynantheine (78), gambirine (79), rotundifoline, yohimbine, pseudoyohimbine (80), a-yohimbine and P-yohimbine, were isolated from U. callophylla [79,80]. Isogambirine is an isomer of the more abundant gambirine and was readily shown to be the 10hydroxy analogue of gambirinefromthe 'H and ,3C NMR spectral data [79]. Gambireine on the other hand was shown to be the C(20) vinyl analogue of gambirine based on the observed molecular ion and the replacement of the ethyl group absorptions by vinyl group absorptions in !H and ,3C NMR [79]. The isolation of isogambirine represents the first instance of a 10-

338

T.-S. Kam

hydroxylated heteroyohimbine from an Uncaria species; hitherto only aromatic substitution at C(9) has been reported for heteroyohimbine alkaloids from Uncaria. V. callophylla appears to be unique in its ability to elaborate hydroxylated heteroyohimbine derivatives and dimeric alkaloids. Of special note is the result of a month-by-month monitoring of the alkaloidal composition of U. callophylla which revealed an interesting seasonal variation of the alkaloid content not recognised before in U. callophylla, in which the amount of the otherwise predominant gambirine diminishes drastically during thefloweringseason [79].

83

82

C0 2 Me OHC 84 R = OMe 85 R = H

C0 2 H

86 R = OMe 87 R = H

A detailed study of the previously uninvestigated U. borneensis was also carried out. The major alkaloids were the tetracyclic oxindoles isorhynchophylline, rhynchophylline, isocorynoxeine, and corynoxeine accompanied by minor yohimbine alkaloids, pseudoyohimbine, alloyohimbine and 3-e/w-P-yohimbine (81). The unique and predominant occurrence


339

of gambirine in U. callophylla has also allowed the development of a simple TLC method for distinguishing this species from the group of taxonomically related species which include besides U. callophylla, U. gambir, U. elliptica and U. acida which has caused some problems in the past. Roxburghines were also not detected in any of the Malaysian U. elliptica samples investigated [79], which is in agreement with the results of a previous study of the Thai species [76]. Only one species from the genus Mitragyna appears to have been investigated, v/z., Mitragyna speciosa which has received much attention in Thailand due to its widespread use as an opium substitute although the pharmacological basis of its narcotic effect remains unclear. A new heteroyohimbine, 3-dehydromitragynine (82) was isolated from fresh leaf samples, in addition to various alkaloids previously known from this species such as mitragynine (83), paynantheine, speciogynine, speciociliatine and mitraciliatine [81]. The 'H NMR spectrum indicated a 9-methoxylated tetracyclic heteroyohimbine and the UV spectrum suggested additional conjugation compared with mitragynine-like compounds, the observed bathochromic shift suggesting the presence of a quaternary nitrogen. Furthermore, the NMR spectrum showed downfield shifts for the H(15) methine and the H(5), H(14), and H(21) methylenes compared with those of mitragynine, suggesting the presence of an unsaturated bond in the vicinity. These observations led to the proposed structure 82 which was further supported by its ready reduction (NaBF^) to mitragynine (83) as well as by its facile formation via oxidation {Pb(OAc>4} of mitragynine. A subsequent study of very young leaf samples has resulted in the isolation of four additional new alkaloids which were the highly conjugated indoles, mitragynaline (84) and corynantheidinaline (85), and the related compounds mitragynalinic acid (86) and corynantheidinalinic acid (87) [82]. The NMR spectral data of 84 indicated the presence of a 9methoxy-substituted indole ring, methoxycarbonyl and ethyl side chains and an aldehyde function. The intense yellow color and the high wavelength maximum (490 nm) observed in the UV spectrum, indicated a highly conjugated system. The ,3C NMR spectrum showed five quaternary carbon resonances (including one amide carbonyl) which were additional to those of the indole system suggesting the presence of another aromatic ring. This observation together with the loss of the C(3) methine resonance when compared with mitragynine indicated that ring D is aromatic. The position of the aldehyde group was deduced from the observed NOE interaction between the aldehyde-H and H(12) as well as the ester OMe. The location of the aldehyde function is similar to that in the known compound nauclefidine which also has a similar UV spectrum as 84. As in the case of 84, the intense color and long wavelength absorption peaks in the UV spectrum of mitragynalinic acid (86) indicated the presence of a highly conjugated structure. The similarity of the NMR spectra with respect to the indole and ring C portions indicated similarity with mitragynaline (84). Notable differences were the absence of signals due to the ester methoxy and the amide carbonyl function and the appearance

340

T.-S. Kam

of new peaks attributable to another aldehyde and a carboxylic acid group. The 13C NMR showed another two additional signals at 5 S3 (methylene) and 5 35 (methine) and analysis of the COSY spectrum indicated these to be part of a CH2-CH-CH2 fragment corresponding to C(17)-C(16)-C(19). The spectral data also indicated the presence of another quaternary carbon at 5 122 which is ascribed to C(20) to which the aldehyde and acid groups are attached. Corynantheidinaline (85) and corynantheidinalinic acid (87) were readily shown to be the 9-demethoxy analogues of mitragynaline (84) and mitragynalinic acid (86), respectively, from the spectral data. The finding in the case of M. speciosa that the alkaloidal composition in young leaves can be significantly different from that in mature leaves raises the interesting possibility that similar variation may also be shown by many other plants for which chemical studies were mainly carried out on mature leaf samples.

88

89

Besides 3-e/?/-P-yohimbine (81) from Uncaria borneensis [79], another new yohimbine derivative is 19,20-dehydro-Oacetyl-yohimbine (88) which was obtained in minute amount from Alstonia angustifolia [83]. The spectral data suggested that it is a dehydro-derivative of the known O-acetyl-yohimbine (89) which was also present in the plant. The location of the additional unsaturation was deduced to be at C(19), C(20) instead of C(20), C(21) since the IR spectrum did not show any enamine band. Due to paucity of material however, the configuration at C(16) and C(17) could not be established. Ajmaline-sarpagine, strychnine and related alkaloids A new vincamajine ester, 4,-hydroxy-3,,5,-dimethoxybenzoylvincamajine (90) was obtained from the roots of Alstonia angustifolia, in addition to nine other known alkaloids, alstonerine, alstophylline, vincamajine, villalstonine, macralstonine, pleiocarpamine, macrocarpamine, norfluorocurarine and 11-methoxyakuammicine [84]. The UV spectrum of 90 was similar to

341


that of vincamajine (91) and the presence of a phenolic function was indicated by the observed bathochromic shift on addition of NaOH. The mass spectrum showed fragments typical of vincamajine esters (vicamajine and arylacyl fragments) and the ! H NMR spectrum was similar to that of vincamajine except for the presence of the aromatic (8 7.15) and methoxy resonances (8 3.92) due to the aromatic acid component and the downfield shift of H( 17) (8 5.58 versus 8 4.25 in vincamajine). The antiamoebic and antiplasmodial activities of the alkaloids were also investigated (vide infra).

90

91

In another study of the leaves of the same plant, several new monomeric alkaloids were obtained (in addition to bisindoles, vide infra) including the macroline alkaloid, 19,20-dehydro10-methoxytalcarpine(92) and 11-hydroxystrictamine (93) [83]. The spectral data of 92 were characteristic of a 10- or 11-methoxylated macroline and somewhat reminiscent of that of alstophylline (94). Both had the same composition and displayed similar mass-spectral fragmentation. As the 'H NMR spectrum gave broad signals, the location of the methoxy group at C(10) was deduced from the ,3C NMR data. The signal of H(21) (aldehyde) was observed as a singlet at 8 9.65 and that of the 18-methyl group as another singlet at 8 2.18. The proposed structure was in agreement with the COSY spectrum as well as the l3C NMR spectrum which was assigned by comparison with villalstonine. The structure of 11-hydroxystrictamine (93) was established by comparison of the spectral data with that of 10-hydroxystrictamine. A study of A. angustifolia from Indonesia resulted in the isolation of two new quaternary indole alkaloids, alstogustine (95) and 19-epialstogustine (96) from the water-soluble portion of the AcOH-MeOH extract of the stem-bark [85]. These alkaloids were characterized as their

342

T.-S. Kara

chlorides. The methanol-soluble portion gave four new alkaloids, AT(b)-demethylalstogustine (97) and the Af-oxides of pseudoakuammigine, akuammicine and jV(b)-demethylalstogustine (98)

92

93

94

95

98 A/(b)->0

Two new oxindoles, iVb-demethylalstophyllal oxindole (99) and alstonal (100), together with three known oxindoles jVb-demethylalstophylline oxindole (101), alstonisine (102), and talcarpine were isolated from Alstonia macrophylla occurring in Sabah, Malaysian Borneo [87]. Compound 99 is an isomer of the known 101. The NMR spectral data were similar to those of 101 except for the appearance of an aldehyde function and a vinylic methyl group in place of an

343


acyl group and the 19-vinylic hydrogen. Alstonal (100) was readily deduced to be the 11demethoxy derivative of compound 99 from the spectral data. A previous investigation of Alstonia macrophylla from Thailand gave vincorine, cathafoline and its /V-oxide, 11-methoxyakuammicine and its N-oxide, vincamajine, alstophylline, Af(4)-demethylalstophylline oxindole, vincamajine 17-0-veratrate and vincamajine Af(l)-tri-0-methylgallate [88], while a very recent study provided two new bisindoles [89].

99 R = OMe 100 R = H

101 R = OMe 102 R = H

Ervatamia polyneura provided a total of 23 alkaloids, mainly of the vobasine- and coronaridine-type. Of these, two represent new alkaloids of the vobasine-type, vobasenal (103) and 16-ep/-vobasenal (104) [90]. Vobasenal was obtained from the leaves while \6-epivobasenal was obtained from the stem-bark extract. Both compounds had similar composition and showed similar UV and IR spectral data. The NMR spectra of 103 showed besides the NH and aromatic signals, other signals characteristic of a vobasine skeleton except that the signals corresponding to an ethyl or ethylidene side chain and to H(21) were absent, being replaced instead by signals due to a vinylogous formamide unit (singlets at 8 7 and 9). The structures were in agreement with the ,3C NMR data which showed signals due to the vinylogous formamide unit at 5 185, 116 and 152 corresponding to C(19), C(20) and C(21), respectively. The configuration at C( 16) of the epimers was distinguished by the signal due to the ester methyl which was more shielded in vobasenal (5 2.82) compared with 16-epi-vobasenal (8 3.52). These compounds are notable for the loss of a carbon atom from the basic vobasinyl skeleton. Six new monomelic alkaloids were isolated from the root bark and leaves of Ervatamia hirta, of which five (105, 106, 109 - 111) possess the normacusine B-affmisine skeleton while the other (112), is the Af-oxide of norfluorocurarine [91]. Compounds 105 and 106 were readily identified as the C(16) epimers of normacusine B and affinisine, respectively, by comparison of their NMR spectral data with that of normacusine B (107) and affinisine (108). Similarly, compounds 109 and 110 were readily shown to be the O-acetyl derivative of 16-e/?i-affinisine and the N-oxide of affinisine, respectively. The remaining new alkaloid, dehydro-16-e/?/-

344

T.-S. Kam

affinisine (111), was shown to have a hexacyclic structure resulting from additional ring formation between C(6) and the C(17) oxygen of 16-epz-affinisine. This was supported by the observation of the oxymethine H(6) and C(6) signals at 6 5.6 and 71.4, respectively. Me0 2 C x

0 2 Me

H

CHO

CHO H 104

103 HOHoC

105 R = H 106 R = Me

H2OH

H

107 R = H 108 R = Me

H2OH

AcOH2Q

109

110 R = Me, A/(4HO


345

Kopsia deverrei in addition to providing several new aspidofractinine-type compounds (vide infra) also gave three other new indole alkaloids, the pleiocarpamine derivative, 16hydroxymethylpleiocarpamine (113), the akuammiline alkaloid, 16-e/?/-deacetylakuammiline (115) and the condylocarpine derivative, 14ot-hydroxy condylocarpine (117) [92]. The !H NMR spectrum of 113 was similar to that of pleiocarpamine (114) except for the absence of the H(16) signal. Instead, the presence of a pair of AB doublets at 8 4.5 and 4.2 with J 12 Hz and the observation of a M - 31 fragment in the mass-spectrum suggested the presence of a hydroxymethyl function at C(16). The C(16) configuration however could not be established due to the relative instability and paucity of material. Compound 115 had similar spectral data as deacetylakuammiline (116) and was readily identified as the C(16) epimer from the downfield shift of the H(17) signal (8 4.35) in !H NMR compared with the corresponding H(17) signal of deacetylakuammiline (8 2.91). Compound 117 was readily identified as 14ahydroxycondylocarpine based on comparison of its spectral data with that of condylocarpine (118). The ,3C NMR spectrum differed from that of condylocarpine in the signal for C(14) which appeared as a deshielded methine at 8 69.6. The stereochemistry of C(14) was deduced from the observed H(14)/H(3) and H(14)/H(15) coupling constants which are consistent with anaxialC(I5)-OH. The leaf extract of Alstonia scholar is gave in addition to the known alkaloids nareline methyl ether (120), picrinine and scholaricine (123), three new alkaloids, v/z., nareline ethyl ether (121), 5-e/?/-nareline ethyl ether (122) and scholarine-N-oxide (124) [93]. Compound 121 was obtained as colorless needles and the UV spectrum showed absorption maxima at 216 and 256 nm indicating the presence of an unsubstituted indolenine chromophore which was confirmed by the resonance at 8 184.5 in the ,3C NMR spectrum attributable to an imine carbon. The *H and ,3C NMR spectra were similar to those of the previously known nareline methyl ether except for the replacement of the C(5)-OMe signals with signals due to the ethyl ether function. The signal due to H(5) was observed as a singlet (8 3.91), which was also the case for the methyl ether derivative (8 3.82), indicating the absence of vicinal coupling due to

346

T.-S. Kam 17

MeOaC.

^HgOH

16)

hAeOzC^ '""R

113 R = CH20H 114 R = H HOHgC

115

jCOgMe

C02Me

117 R=:OH 118 R=rH

116

17

1"

C02Me

A.

r^f^

1 ^

14

21

\'=^'^'^^

^N 5

C02Me 0

119 120 121 122

R1=H,

R2=0H

R U H , R2=0Me R U H , R2=0Et R ^ = 0 Et, R2 . = H

123 R = OH 124 R = OMe,/V(4)-^


347

the H(5)/H(6) dihedral angle of ca. 90°, in agreement with the structure of nareline (119) previously established by X-ray analysis. Compound 122 had UV and mass-spectral data which were similar to that of 121. The *H NMR spectral data were also similar to that of 121 except for significant changes involving H(5) and the ethyl group resonances, suggesting a change in the configuration at C(5). This was also reflected in the ,3C NMR spectral data which were similar to those of 121 except for significant changes in the shifts associated with C(5) and C(6). The signal due to H(5) in 122 was a doublet with J 3 Hz and shifted to lower field at 8 5.14 which is consistent with the change in configuration of the C(5) ethoxy substituent resulting in a dihedral angle of ca. 45°. The signal due to the ethoxy group in 122 has also undergone a significant upfield shift to 5 0.45 as a result of anisotropy exerted by the aromatic ring due to the change in the stereochemistry of the ethyl ether substituent. Nareline (119) and its congeners were first isolated from an Indian sample of A. scholaris [94] and since then, have also been obtained from samples from Taiwan (cultivated) [95,96] and Thailand [96]. The alkaloidal composition of Alstonia scholaris from Pakistan [97,98], the Phillipines [96,99], and Thailand [96,100,101] have also been examined and comparison of the alkaloidal composition indicated affinity of the Indian-Thai-Malaysian species which are characterized by predominance of nareline- and akuammicine-picrinine-type alkaloids [93,94,96,102]. The alkaloidal pattern of the Phillipine-Indonesian samples appear different [96,99] and arc distinguished by the common occurrence of the 6,7-seco-angustilobine B-type compounds {e.g. 6,7-jeco-angustilobine B (125) and 6,7-5eco-19,20-epoxyangustilobine B (126)} which are not present in the Indian-Thai-Malaysian samples. In addition, the Indonesian A. scholaris also contains the ring-opened aspidosperma-type alkaloid, leuconolam (172), which is not present in any of the other Asian A. scholaris samples [96]. It is perhaps pertinent to note that similar 6,7-$eco-angustilobine B-type alkaloids have also been obtained from another Indonesian Alstonia (A. angustiloba) [103] although similar compounds were not detected from an examination of the Malaysian samples.

125

126

348

T.-S. Kam

Ervatamine and uleine alkaloids The ervatamine and uleine group of alkaloids are distinguished by their lack of the characteristic two-carbon tryptamine bridge, a feature they share in common with pericalline and ellipticine. Ervatamine-type alkaloids were first obtained from the Australian plant Ervatamia orientalis which yielded ervatamine (127), 20-e/H-ervatamine (128) and 19,20dehydroervatamine (129) [104]. Since then other ervatamine-type alkaloids have been obtained from other species of Tabernaemontana (Ervatamia) and Hazunta. The Malaysian E malaccensis gave in addition to dregamine, six other alkaloids of the ervatamine type, including 19,20-dehydroervatamine, 20-e/?/-ervatamine, methuenine (130), 16-epi-methuenine (131), 6oxo-methuenine (132), Af( 1 )-methoxy- 19,20-dehydroervatamine (133) and N( 1 )-methoxymethuenine (134) [105]. The last two compounds, which are N( 1 )-methoxylated derivatives of 19,20-dehydroervatamine and methuenine, respectively, were new alkaloids. These compounds showed UV (acyl indole chromophore) and NMR spectral data which were characteristic of the ervatamic skeleton but instead of signals due to the indole NH or NMe, there was present a low field 3H signal due to a Af-OMe group (SH 4.2; 5c 66). Substitution by methoxy on the indolic nitrogen was further confirmed by the observation of NOE between N-OMe and the aromatic H(12). The N(l)-methoxylated alkaloid 133 was first reported by Goh from a Tabernaemontana species identified as T corymbosa [106]. Compounds 129, 130, 133 and a new ervatamine alkaloid, 5-oxo-19,20-dehydroervatamine (135) were subsequently also reported from another sample identified as T corymbosa [107]. Compound 135 showed spectral data characteristic of the ervatamic skeleton except for the additional presence of an amide carbonyl (5c 167.7) which was located in the 7V(4)-containing ring D since the carbon resonances in this ring were significantly shifted whereas those of the rest remained essentially unchanged when compared with compound 129. The alternative location of the amide carbonyl function at C(21) was ruled out since the long-range coupling between Me(18) and H(21), which is a common feature of compounds 129,130 and 133, was also observed in the lH NMR spectrum of compound 135. The isolation of compound 135 represents the first instance of oxygenation at position 5 of the ervatamic skeleton, oxygenation at position 6 being previously the more common [107]. It is likely from the similar alkaloidal composition obtained, and considering the well known taxonomic difficulties associated with the Tabernaemontana (Ervatamia) [108], that all three samples belong to the same species. There has only been one reported instance of an uleine-type alkaloid from a Malaysian plant. Undulifoline (136), was obtained from the new Malayan Alstonia species, Alstonia undulifolia Kochummen and Wong, in addition to tetrahydrocantleyine, cantleyine, akuammicine, pieiocarpamine, echitamidine, 20-e/?M9£-echitamidine, echitamine and nor-echitamine [109].

349


130 R1 = H-p, R2 = H 2 131 R1 = H-a, R2 = H 2 132 R1 = H-P, R2 = 0

127 R = p-Et 128 R = a-Et 129 R = CHMe

Me

rVî OMe O

133 R = C0 2 Me 134 R = H

135

The mass spectrum of 136 displayed besides a strong M+ ion (m/z 340), another intense peak at m/z 238 which arose from cleavage of the C(21)/N(4) bond followed by aromatization of ring C, in analogy to the mass-spectral fragmentation of uleine. The NMR spectral data were consistent with the proposed structure, showing an unsubstituted indole nucleus and presence of a methyl ester and of a N(4)-methyl group, while ethyl, vinyl or ethylidene side chains were absent. The ,3 C NMR spectrum showed two methyls, five methylenes (two oxymethylenes), three methines and one quaternary carbon. Analysis of the COSY spectrum revealed besides the presence of an isolated methylene, the existence of the partial structure OCH2CH2CH(CH)CHCH2CH2 which was consistent with the proposed structure of undulifoline. The relative configuration of C(16) and C(20) were fixed by the CH2OCH2 bridge between these two centres while the bridging of ring C in a 1,3 manner by piperidine and oxepane rings required these rings to be on opposite sides of the molecule. The presumed

350

T.-S. Kam

common origin of undulifoline and tubotaiwine from precondylcarpine allowed the tentative assignment of the absolute configuration of undulifoline as being similar to that of tubotaiwine (137).

136

137

Ebumane alkaloids Alkaloids of the ebumane group have been obtained only from the Apocynaceae and in the case of Malaysian plants, predominantly from plants of the genus Kopsia and Leuconotis. Kopsia larutensis gave predominantly alkaloids of the eburnane-type [110-112], including (+)eburnamonine (138), (+)-eburnamonine-N-oxide, (-)-ebumamine (139), (+)-isoeburnamine (142), (-)-O-ethyleburnamine (140), (+)-eburnamenine (145), (-)-kopsinine and two new alkaloids, larutensine [110] (larutenine [112]) and eburnaminol [110]. Larutensine (154) is isomeric with (+)-ebumamonine (138), the predominant alkaloid found in the leaves. The UV spectrum indicated an unsubstituted indole and the IR spectrum indicated absence of NH/OH functions and presence of an ether function. The ! H and ,3C NMR spectral data indicated an ebumane derivative oxygenated at C(16) (5c 77.5; 8H 5.83) but differing from the other ebumane alkaloids occurring in the plant in that the C(20) ethyl substituent was missing. The presence instead of carbon resonances at 6 58.5 (-CH20-) and 40.6 (-CH2CH20-) suggested that ring formation had occurred in which an ether oxygen now links C(18) to C(16). This was supported by the C(18) hydrogens which were shifted to 8 3.80 and 3.95. The proposed structure was in accord with the 2-D NMR data. The configuration at C(20) and C(21) were assumed to be similar to those in the other ebumane alkaloids isolated on biogenetic grounds. This being the case, the stereochemistry of the C(16) ether oxygen has to be p to permit formation of the six-membered ring. The likely precursor of larutensine, eburnaminol (155), was also isolated from K. larutensis, but as pointed out by Lounasmaa [113,114] and Kam [115], the original structure proposed {C(16)-a-OH} required amendment. The absolute configuration of C(16) of the ebumane group of alkaloids has also been established based on X-ray analysis of (-)-O-ethyleburnamine (140) and (+)-isoeburnamine (142), representing the ebumamine and


351

isoeburnamine (epieburnamine) series, respectively (Table 2) [115]. It has also been pointed out that the coupling constants for the H(16) doublet of doublets can be of diagnostic value since the pentacyclic compounds of the eburnamine series invariably have J 9 and 5 Hz, while the corresponding coupling constants in the diastereomeric isoeburnamine (epieburnamine) series are invariably 4 and 2 Hz due to H(16) being axial and equatorial, respectively, when ring E is in the preferred chair conformation [115]. Table 2. Absolute configuration of the eburnane alkaloids

(+)-eburnamonine (138) (-)-eburnamine (139) (-)-Oethyleburnamine (140) (-)-O-methyleburnamine (141) (+)-isoeburnamine (142) (+)-0-etnylisoeburnamine (143) (+)-0-methylisoeburnamine (144) (^)-eburnamenine (145)

138 139 140 141 142 143 144 145

R\R2 = 0 R1 = OH, R2 = H R1=OEt, R 2 = H R1= OMe, R2 = H R 1 =H, R2 = OH R 1 =H, R 2 =OEt R 1 =H,R 2 = OMe R 1 =H,R 2 = nil,A 16 ' 17

(-)-eburnamonine (146) (+)-eburnamine (147) (+)-0-ethyleburnamine (148) (+)-0-methyleburnamine (149) (-)-isoeburnamine (150) (-)-Oethylisoeburnamine (151) (-)-O-methylisoeburnamine (152) (-)-ebumamenine (153)

146 147 148 149 150 151 152 153

R\R2 = 0 R1 = H, R2 = OH R 1 =H, R2 = OEt R 1 =H, R2 = OMe R 1 =OH, R2 = H R1=OEt, R 2 =H R 1 =OMe, R2 = H R 1 =H,R 2 = nil,A 16 ' 17

352

T.-S. Kam

CH2OH 154

155

The structures of eburnaminol (155) and larutensine (154) have been confirmed by a synthesis reported by Lounasmaa from the previously available indoloquinolizidine ester 156 (Scheme 8). Successive reduction, acetylation and Fujii oxidation of 156 yielded the enamine 157 which was alkylated with iodoacetic ester followed by NaBH4 reduction to give a mixture of four products. Treatment of two of these, the epimeric esters 158, with ethanolic sodium ethoxide resulted in cyclization to 18-hydroxyeburnamonine (159) accompanied by its C(20) epimer. Reduction of 18-hydroxyeburnamonine furnished (±)-eburnaminol and 16-epieburnaminol (160) which on overnight treatment with acid gave (±)-larutensine [114]. Another new ebumane alkaloid recently obtained is (+)-19-oxoeburnamine (161) from Kopsia pauciflora [116]. The presence of the C(20)-acetyl side chain was indicated by the observed base peak due to loss of water and the acetyl side chain in the mass-spectrum and by the replacement of signals due to the C(20)-ethyl group by signals due to an acetyl group in the 'H and ,3C NMR spectra when compared with eburnamine. The configuration at C(21) and C(20) were assumed to be similar to that of (-)-eburnamine (139), (+)-isoeburnamine (142) and (+)-eburnamonine (138) which were also obtained, while the observed coupling constants for the H(16) doublet of doublets (J 9, 5 Hz) allowed the configuration at C(16) {C(16)-P-OH} to be established [116]. The Malaysian Borneo species, Kopsia dasyrachis, also furnished several ebumane alkaloids including (+)-ebumamonine (138), (+)-isoeburnamine (142) and (+)-19(/?)hydroxyeburnamine (162). The latter was a new alkaloid and X-ray diffraction was undertaken to establish the configuration at C(19) [117]. The occurrence of (+)-eburnamonine and (+)isoeburnamine in the same plant indicated that 162 belongs to the same enantiomeric group possessing the 20p, 21(3 configuration, and the observed coupling constants of the H(16) doublet of doublets of 10 and 5 Hz indicated that the C(16)-OH is p. This compound also occurs in K. pauciflora [118] and constitutes the ebumane half of the dimeric alkaloid kopsoffmol which also occurs in K. dasyrachis [117]. In view of the structure of 162, it would appear that an alternative and more likely structure for kopsoffinol is 312 in which the 19(/?)hydroxyeburnamine unit constitutes the ebumane half (vide infra).


i -in

EtQ2C

AcO

156

157

OAc 159

158

VII

155

16-POH

160

16-aOH

(±)-154

Reagents: i, LiAIH4, THF; ii, Ac20, py; Hi, EDTANa2, Hg(OAc)2, EtOH-H20, A; lv, ICH2C02Et; NaBH4; v, NaOEt/EtOH; vi, LiAIH4, THF; vii, 5% HCI, r.t. overnight

SCHEME 8

354

T.-S. Kam

HO^\"H 161

162

OH

T^K

k

163

164

Recently two new dihydroeburnane alkaloids, terengganensines A (163) and B (164), in addition to quebrachamine, isoebumamine, eburnaminol and larutensine were obtained from a new Kopsia species, Kopsia terengganensis [119]. The UV spectrum indicated the presence of dihydroindole chromophores and in common with eburnaminol and larutensine, the NMR spectra indicated absence of NH and ethyl groups, suggesting the presence of an oxidized ethyl side chain. The aromatic C(7) (8 ca. 78) and C(2) (8 ca. 92.5) in these two compounds were quaternary centres and the downfield shifts suggested that the former was a to an oxygen while the latter was linked to both an oxygen and nitrogen. The analysis of 2-D COSY and HMQC spectral data revealed fragments which were in accordance with the proposed structures while long range C-H correlations {H(18)/C(2), C(16)} in the HMBC spectrum of 163 supported the presence of the two ether bridges linking C(18)/C(2) and C(16)/C(2). The observation of Bohlmann bands in the IR and the observed NOE between H(19P) and H(21) indicated transfused C/D and cis fused D/E rings as in larutensine. The configuration at the centres C(21) and C(20) must be similar to the other eburnane compounds present and furthermore the formation of the ether bridges required the C(16)-0 and C(2)-0 bonds to be on the same side of ring E. Finally, a cis B/C junction was required to allow a chair conformation for ring C which fixed the


35*

stereochemistry of the C(7)-OH. Terengganensine B (164) showed similar NMR spectral data as terengganensine A except for absence of the C(16) and C(18) oxymethines. Instead an oxymethylene signal assigned to C(18) and signals due to two olefinic hydrogens typical of 16,17-dehydroeburnamine compounds were observed. This and the UV spectrum (228, 283 and 307 nm) which was consistent with the presence of an Af-arylenamine chromophore, supported the proposed structure of terengganensine B (164). It is of interest to compare the occurrence of the eburnane alkaloids in Malaysian Kopsia with that of the Chinese species [118]. From such a comparison, it would appear that the Malaysian Kopsia (and Leuconotis) species elaborate exclusively eburnane alkaloids of one enantiomeric group (20/?, 21/? or 20(3, 21(3 configuration) [18-20,58,110-112,115-119], while the Chinese species appear to elaborate eburnane alkaloids of the opposite enantiomeric group (20S, 215 or 20a, 21a configuration) [118,120-122]. Notable exceptions are the dimeric alkaloids kopsoffinol and kopsoffine isolated from the Malaysian Borneo species Kopsia pauciflora [124] which were reported to be constituted from union of kopsinine and dihydroeburnamenine units with the 20a, 21 a configuration (vide infra). Iboga alkaloids The iboga alkaloids, exemplified by coronaridine (165), abound in plants of the family Tabernaemontana (Ervatamia) [125]. Although many known iboga-type alkaloids such as for example coronaridine, voacristine, voacangine (166) and eglandine were obtained from examination of Malaysian Tabernaemontana plants, only two new monomelic iboga alkaloids, 3-oxo-19-ep/-heyneanine (167) and 3-hydroxy-3,4-secocoronaridine (168) have been reported, both of which were from E. polyneura (which also provided indole alkaloids of the vobasinetype, vide supra) [90]. The UV spectrum of 167 (227, 285, 293 nm) indicated an indole chromophore and the IR spectrum indicated the presence of NH (3320 cm"1), ester (1720 cm'1) and lactam carbonyls (1650 cm"1). The presence of the lactam function was also indicated by the carbon resonance at 8 173 and suggested a 3-oxo-coronaridine derivative. The NMR spectra were characteristic of coronaridine derivatives possessing the hydroxy ethyl side chain and assignment of the C(19) configuration as R was possible from the observed chemical shift of C(15) (8 28.0) and C(21) (8 53.1) by analogy with those of 19-

Alkaloids: Chemical and Biological Perspectives

Alkaloids: Chemical and Biological Perspectives

Alkaloids: Chemical and Biological Perspectives (Vol. 10)