Studies in Natural Product Chemistry, Volume 20: Structure and Chemistry, Part F, (Including Cumulative Index Volumes 1-20) (Studies in Natural Products Chemistry)

studies in Natural Products Chemistry Volume 20 Structure and Chemistry (Part F) (Including Cumulative Index Volumes 1-20)

Studies in Natural Products Chemistry edited by Atta-ur-Rahman

Vol. 1 Stereoselective Synthesis (Part A) Vol. 2 Structure Elucidation (Part A) Vol. 3 Stereoselective Synthesis (Part B) Vol. 4 Stereoselective Synthesis (Part C) Vol. 5 Structure Elucidation (Part B) Vol. 6 Stereoselective Synthesis (Part D) Vol. 7 Structure and Chennistry (Part A) Vol. 8 Stereoselective Synthesis (Part E) Vol. 9 Structure and Chemistry (Part B) Vol.10 Stereoselective Synthesis (Part F) Vol.11 Stereoselective Synthesis (Part G) Vol.12 Stereoselective Synthesis (Part H) Vol.13 Bioactive Natural Products (Part A) Vol.14 Stereoselective Synthesis (Part I) Vol.15 Structure and Chemistry (Part C) Vol.16 Stereoselective Synthesis (Part J) Vol.17 Structure and Chemistry (Part D) Vol.18 Stereoselective Synthesis (Part K) Vol.19 Structure and Chemistry (Part E) Vol.20 Structure and Chemistry (Part F)

Studies in Natural Products Chemistry Volume 20 Structure and Chemistry (Part F) (IncludingCumulative Index Volumes 1-20)

Edited by

Atta-ur-Rahman

H.E.J. Research Institute of Chemistry, University of Karachi, Karachi 75270, Pakistan

1998

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First edition 1998 Library of Congress Cataloging in Publication Data A catalog record from the Library of Congress has been applied for. ISBN: 0-444-50105-3 ® The paper used in this pubUcation meets the requirements of ANSI/NISO Z39.48-1992 (Permanence of Paper). Printed in The Netherlands.

FOREWORD

Natural Product Chemistry continues to grow at an increasing pace and this growth is reflected in the present volume of Studies in Natural Product Chemistry which is the 20^^ of this series. The first 20 volumes were largely devoted to structure and synthesis of various classes of natural products, irrespective of their bioactlvity. Subsequent volumes of this series will however be devoted to the chemistry of bioactive natural products and will therefore represent a departure from the earlier volumes. The present volume contains contributions from a number of eminent scientists and covers Interesting reviews on terpenes, alkaloids and other types of natural products reported from terrestrial and marine sources. It is hoped that this volume will be received with the same enthusiasm and Interest as the previous volumes of this series. Comprehensive Indexes covering all the 20 volumes, have been prepared and they include a Cumulative General Subject Index along with more focused Cumulative Indices on Organic Synthesis, Pharmacological Activity and Biological Source. This comprehensive indexing of the volumes should make the entire series much more valuable and user-friendly. I would like to express my thanks to Dr. Farzana Akhtar, Dr. Farhana Noor-e-AIn, Mr. Zaheer-ul-Haq, and Miss Rehana Shah for their assistance in the preparation of the Index. I am also grateful to Mr. Waseem Ahmad for typing and to Mr. Mahmood Alam for secretarial assistance.

Atta-ur-Rahman

Ph.D. (Cantab), Sc.D. (Cantab)

July 31. 1998

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PREFACE Volume 20 of this well known series entitled: "Studies in Natural Products Chemistry", continues the high standard of the previous volumes. The 17 Chapters represent a broad spectrum of topics which serve as an excellent overview of the vast array of natural products research continuing on a worldwide basis. The areas covered do not duplicate to any significant extent material covered in previous volumes and indeed present to the interested reader, information which is useful and pertinent to those involved in the highly diverse avenues of natural products. Each of the chapters is well written and brings fonA/ard in review fashion, a particular area of natural products chemistry. The manner of presentation in the majority of chapters allows the linkage of synthetic and structural chemistry with biological applications and relevance. As the area of natural products research continues to expand into these interdisciplinary avenues, the information provided by the authors is particularly useful not only to the specialist but to the scientist wishing to develop a general knowledge of the specific field covered within the Chapter. This Volume, as the previous volumes in this series, is highly recommended as a useful summary of important information which spans the diverse area of biological activity, medicinally Important terpenes, alkaloids, steroidal lactones, carotenoids, natural colourants, peptides and the use of enzymes in the products of chiral synthons.

James P. Kutney

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CONTENTS Foreword

V

Preface

vii

Contributors

xi

Terpenes and their Biological Relevance G.G. HABERMEHL AND W. FLIEGNER

3

Crinitol, an Acyclic Diterpene Diol from Marine Algae I. KUBO AND L.R. SMITH

25

Stereoselective Synthesis of Methylcyclopentanoid Monoterpenes A. BIANCO

41

Chemical Constituents of Taxus Species V.S. PARMAR AND A. JHA

79

Withanolides, Biologically Active Natural Steroidal Lactones : A Review A.S.R. ANJANEYULU, D. S. RAO, P.W. LEQUESNE

135

Natural Products by Oxidative Phenolic Coupling Phytochemistry, Biosynthesis and Synthesis 263 G.M. KESERU AND M. NOGRADI

Narcissus Alkaloids J. BASTIDA, F. VlLADOMAT AND C. CODINA

323

Total Synthesis of Naphthylisoquinoline Alkaloids M.A. RIZZACASA

407

DNA - Damaging Natural Products with Potential Anticancer Activity A.A. LESILE GUNATILAKA AND DAVID G.I. KINGSTON

457

In Vitro Models of Human Disease States J.M. PEZZUTO, C.K. ANGERHOFER AND H. MEHDI

507

Synthesis of Carotenoids H. PFANDER, M. LANZ AND B. TRABER

561

Structure Elucidation of Phenylpropanoid Wood Extractives S. OZAWA, T. SASAYA AND S. NlSHIBE

613

Chemical and Biological Investigations of Salvia Species Growing in Turkey A. ULUBELEN AND G. TOPCU

659

The Chemistry of Some Natural Colourants J.H.P. TYMAN

719

Bioactive Natural and Synthetic Acronycine Derivatives Modified at the Pyran Ring S. MICHEL AND F. TILLEQUIN

789

Chiral Synthons by Selective Redox Reactions Catalysed by Hitherto Unknown Enzymes Present in Resting Microbial Cells H. SIMON AND H. GUNTHER

817

Microcystins and Nodularins Hepatotoxic Cyclic Peptides of Cyanobacterial Origin L. MORODER AND S. RUDOLPH-BOHNER

887

Subject Index

921

CONTRIBUTORS A.S.R. Angerhofer

Professor of Organic Chemistry, School of Chemistry, Andhra University, Visakhapatnam-530 003, India

Cindy Kay Angerhofer

Program for Collaborative Research in the Pharmaceutical Sciences, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy and Department of Surgical Oncology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, U.S.A.

A.S.R. Anjaneyulu

School of Chemistry, Andhra University, Visakhapatnan 530 003, India

Jaume Bastida

Department of Natural Products, Faculty of Pharmacy, University of Barcelona, Avda., Diagonal 643-08028 Barcelona, Catalonia, Spain

Armandodoriano Bianco

Centro di Studio CNR per la Chimica delle Sostanze Organiche, Naturali Dipartimento di Chimica-Universita La Sapienza-Roma, Italy

Carles Codina

Department of Natural Products, Faculty of Pharmacy, University of Barcelona, Avda., Diagonal 643-08028 Barcelona, Catalonia, Spain

W. Fliegner

Chemisches Institut der Tieraztichen, Hochschule Hannover, Lehrgebiet fur Organische Chemie, Bischofsholer Damm 15, HausNr. 123, 30173 Hannover, Germany

Abeysinghe Arachchige Leslie Gunatilaka

Bioresources Research Facility, The University of Arizona, Tucson Arizona, 250 East Valencia Road, Tucson, Arizona 85706, USA

Helmut Giinther

Institut fur Organische Chemie und Biochemie, Universitat Munchen, D-8 5 747 Garching, Germany

G.G. Habermehl

Chemisches Institut der Tieraztichen, Hochschule Hannover, Lehrgebiet fur Organische Chemie, Bischofsholer Damm 15, HausNr. 123, 30173 Hannover, Germany

Amitabh Jha

Department of Chemistry, University of Delhi, Delhi-110 007, India

G.M. Keserti

Research Group for Alkaloid, Chemistry of the Hungarian, Academy of Sciences, P.O. Box 91, H-1521 Budapest, Hungary

Gyorgy Miklos Keserii

Department of Chemical Information Technology, Technical University of Budapest, POB 91, H-1521 Budapest, Hungary

Technische

David George Ian Kingston

Bioresources Research Facility, The University of Arizona, Tucson Arizona, 250 East Valencia Road, Tucson, Arizona 85706, USA

Isao Kubo

Department of Environmental Science, Policy and Management, University of California, 201 Wellman Hall, Berkely California 94720-3112, U.S.A.

Marc Lanz

Department fiir Chemie und Biochemie, University of Berne Freiestr. 3, CH-3012 Berne, Switzerland

P.W. LeQuesne

Department of Chemistry, North Eastern University, Boston, MA 02115, USA

Haider Mehdi

Program for Collaborative Research in the Pharmaceutical Sciences, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy and Department of Surgical Oncology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, U.S.A.

Sylvie Michel

Universite Rene Descartes-Paris V, Faculte De Pharmacie, Laboratoire de Pharmacognosie, U.R.A. au C.N.R.S.N. 1310 4, Avenue de I'Observatoire, 75270 Paris Cedex 06, France

Luis Moroder

Max-Plank-Institut far Biochemie, Am Klopferspitz 18a, D-82152, Martinsried, Germany

Sansei Nishibe

Faculty of Pharmaceutical Sciences, Health Sciences, University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-02, Japan

Mihaly Nogradi

Research Group for Alkaloid, Chemistry of the Hungarian, Academy of Sciences, P.O. Box 91, H-1521 Budapest, Hungary

Shuji Ozawa

Department of Forest Science, Faculty of Agriculture, Hokkaido University, Sapporo 060, Japan

Virinder Singh Parmar

Department of Chemistry, University of Delhi, Delhi-110 007, India

John Michael Pezzuto

Program for Collaborative Research in the Pharmaceutical Sciences, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy and Department of Surgical Oncology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, U.S.A.

Hanspeter Pfander

Department fiir Chemie und Biochemie, University of Berne Freiestr. 3, CH-3012 Berne, Switzerland

D. Satyanarayana Rao

School of Chemistry, Andhra University, Visakhapatnan 530 003, India

Mark A. Rizzacasa

School of Chemistry, The University of Melbourne, Parkville, Victoria 3052, Australia

Sabine Rudolph-Bohner

Max-Plank-Institut fur Biochemie, Am Klopferspitz 18a, D-82152, Martinsried, Germany

Takashi Sasaya

Department of Forest Science, Faculty of Agriculture, Hokkaido University, Sapporo 060, Japan

Helmut Simon

Institut fur Organische Chemie und Biochemie, Universitat Munchen, D-85747 Garching, Germany

Leverett R. Smith

Department of Environmental Science, Policy and Management, University of California, 201 Wellman Hall, Berkely California 94720-3112, U.S.A.

Francois Tillequin

Universite Rene Descartes-Paris V, Faculte De Pharmacie, Laboratoire de Pharmacognosie, U.R.A. au C.N.R.S.N. 1310 4, Avenue de I'Observatoire, 75270 Paris Cedex 06, France

Giilacti Topcu

Department of Chemistry, Tubitak, Marmara Research Center, P.O. Box 21, 41470, Gebze-Kocaeli, Turkey

Bruno Traber

Department fur Chemie und Biochemie, University of Berne Freiestr. 3, CH-3012 Berne, Sv^itzerland

John Henry Paul Tyman

Department of Chemistry, Brunei University West London, Uxbridge, Middlesex UB8 3PH, U.K.

Ayhan Ulubelen

Department of Chemistry, Faculty of Pharmacy, University of Istanbul, 34452 Istanbul, Turkey

Francese Viladomat

Department of Natural Products, Faculty of Pharmacy, University of Barcelona, Avda., Diagonal 643-08028 Barcelona, Catalonia, Spain

Technische

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Structure and Chemistry

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Atta-ur-Rahman (Ed.) Studies in Natural Products Chemistry, Vol. 20 © 1998 Elsevier Science B.V. All rights reserved.

Terpenes and their Biological Relevance G.G. Habermehl and W. Fliegner 1.

INTRODUCTION Terpenes are a large group of natural products, occurring mainly in higher

evolved plants as secondary metabolites. The occurrence in higher evoluted plants only may be understood as a consequence of phylogenesis. Under the pressure of selection from herbivorous animals, the synthesis of substances with repellent properties has been necessary in order to make possible a coexistence of different plant and animal species. The first chemical deterrence mechanisms were of an unspecific kind. The synthesis proceeded via the shikimic acid pathway which was already completely developed in gymnosperms. One example of this is the synthesis of lignin. Lignin is one of the most abundand contents of wood, varying between 18 and 30 %. Although its main property is the formation of the stroma, it possesses some antifungal and insectizide properties. By the shikimic acid pathway phenols and tannins are formed, too, to prevent an attack from microorganisms and animals. During the following evolution this pathway has been left stepwise, until in the angiosperms the acetate-mevalonate pathway dominated. This pathway in angiosperms has opened an immense chemical source to specifically acting poisons and repellents, many of them being terpenes. This invention was followed by intense evolutionary interactions between plants and animals, yielding that high diversity of angiosperms, and at the same time, animal species since about 100 million years ago. About 65 million years ago this development of plants was perfect, and the angiosperms predominant. This evolution of poisonous substances in plants coincides with the extinction of the dinosaurs. If one looks closer to this event, one may observe that there has been no complete extinction; many of the saurians survived in one way or another. For example, our birds come from flying saurians; the close connection between the birds and the reptiles of today can be seen in their closely related physiology, leading to the zoological classification of "Sauropsidae", enclosing both, reptiles and birds. And if you have a look at the saurians of today, nearly all of them are carnivorous. All these facts may lead to the conclusion that the herbivorous saurians only became extinct. This is supported by the fact that the dinosaurs did not disappear within a short period of time, as one should accept if this was due to a cosmic event, or a big vulcanic eruption, but within a million of years or so. All these observations fit together, if one accepts that the complete change in

the plant kingdom, together with the newly developed substances led to the end of the dinosaurs. The new physiology with the new acetate-mevalonate pathway gave the opportunity to the plants to produce a tremendous amount of substances acting as protecting agents. 2.

TERPENES AND THEIR ACTIVITIES 2.1 Terpenes as Repellents In a few cases only, the topical situation (spines, thorns) is of protective

value against herbivores. The most potent and effective chemical repellents against these animals are those producing pain or discomfort because of a bad taste or smell. Typical examples are the irritating diterpene-esters from Euphorbiaceae or from Thymelaeaceae (1), or the toxic bitter principles from the Cucurbitaceae, e.g. the Cucurbitacines (2). There are also numerous terpenes acting as contact allergens with serious skin irritations, like the sesquiterpenelactones from Asteraceae (3). Sometimes substances may be effective even after consumption, provided that the animal can recognize the connection between feed and result. In many cases this is not true and, therefore, not a protection. It is well known that cattle or horses like to eat outside the fence, even if they are on a good meadow, either for curiosity or instinct of play. Good examples are here andromedotoxin from Rhododendron

and Andromeda

species, or the

terpene-alkaloids from Aconitum, belonging to the most potent plant toxins. 2.2 Resistance Formation Microorganisms are able to establish resistances because of their great genetic flexibility, the short generation times, and intraspecific as well as interspecific gen exchange. A generally known example of this capability is the resistance against therapeutically used antibiotics. But insects, too, are able to adapt to chemical repellents, even using such substances for their own defense, as is well known from ants and beetles.In such cases a substance which should protect its producer (allomone) becomes a substance useful for the attacker (kairomone), (4, 9). 2.3 Underground Competition Not only animals but also plants are competing in the struggle for the best conditions of life, and they use chemical defense mechanisms, too. Some plants are able to set free germicides directly from the roots. Another mechanism is to exsude from the surface of the leaves such substances which come into the earth by the rain (5). Typical examples are Salvia

leucophylla

and

Artemisia

californica. These shrubs suppress the growth of any plants within a radius of 1 meter completely, by excretion of 1.8-cineol and campher; these substances

inhibit the growth up to a distance of 9 meters (6). 2.4 Terpenes as Signal Substances Terpenes are also used as signal substances, especially with ants but also with other insects. Farnesol is used as male attractrant (7), Citral, geraniol, nerolic acid, and geranic acid are used to transmit information on feed sources (8). These substances, mostly monoterpenes, and sesquiterpenes are produced by plants and taken up by the insects who store them in special glands from which they are released according to their needs. These mechanisms have been developed in a most sophisticated way by ants, butterflies, and beetles (9). Using mixtures of terpenes in different concentrations, they have established a real "chemical language". 2.5 Activities within the Plants. Some terpenes act as plant hormones, e.g. as growth regulators. Such regulators are the brassinolides, steroids with a seven-membered lacton ring B as well as two vicinal diol functions in ring A, and in the side chain (10). The brassinosteroids show in submicromolar concentrations a complex physiologic activity spectrum, e.g. a raise in resistance against stress factors like heat, cold, drought or phytopathogenic infection. The biochemistry of these effects has been studied in detail (11).

3.

TERPENES AS PLANT POISONS AND REPELLENTS. 3.1 General aspects Among all the activities of terpenes from plants, their toxicity is most

important for several reasons. One aspects is their role in ecology as protection of the plants, the other is the economic aspect and also the health aspect, as terpenes are involved in quite a number of envenomations. Envenomations in humans are not rare; mostly children are involved who eat or suck berries or leaves. However, in an increasing number, also adults are involved. On the "green wave" they collect herbs and roots by themselves, considering them "more healthy" than the commercial ones, but confounding them with dangerous species. In the same way therapeutics from plants are estimated harmless for being "natural remedies", and envenomation occurs, frequently due to an overdose.But in most of the cases animals are involved, not only grazing animals but also small animals at home. In the following section the most important plants with terpenes as toxins will be presented together with their chemistry and the symptoms of poisoning.

3.2 Family: Apicaceae Sium latifoliurriy Water parsnip. The plant is abundand in Central Europe but occurs also in the rest of the continent, and also in parts of Africa. The fruit contains (6-7%) of a mixture of limonen (80 %), perillaaldehyde (6%),oc-, and B-pinene, 6-bisabolon, and c?