Advances in Carbohydrate Chemistry and Biochemistry, Volume 46

Advances in Carbohydrate Chemistry and Biochemistry Volume 46

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Advances in Carbohydrate Chemistry and Biochemistry Editors R. STUART TIPSON

DEREK HORTON

Board of Advisors LAURENSANDERSON STEPHEN J. ANCYAL HANSH. BAER CLINTONE. BALLOU JOHN S. BRIMACOMBE

GUY G. S. DUTTON BENGTLINDBERG HANSPAULSEN NATHANSHARON ROY L. WHISTLER

Volume 46

ACADEMIC PRESS, INC. Harcourt Brace Jovanovich, Publishers

San Diego New York Berkeley Boston London Sydney Tokyo Toronto

COPYRIGHT 0

1988

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ACADEMIC PRESS,

INC.

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NUMBER: 45-11351

CONTENTS PREFACE. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Konoehin Onodera, 1910-1983 TOHRUKOMANO AND

NAOKI KASHIMURA

Text

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Venancio Deulofeu, 1902-1984 ROSAM. DE LEDERKREMER AND Text

EDUARDO G. GROS

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11

High-Performance Liquid Chromatography of Carbohydrates KEVINB. HICKS

I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11. Instrumentation and Stationary Phases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111. Separations and Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . IV. Special Aspects and Problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

17 18 32 63

N.M.R. Spectroscopy of Fluorinated Monosaccharides RENE CSUKAND BRIGITTEI. GLANZER 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11. Spectroscopy of Fluorinated Monosaccharides. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111. Tables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

73 74 80

Applications of Photosensitive Protecting Groups in Carbohydrate Chemistry

URI ZEHAVI 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11. Hydroxy Functions, Including Diols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111. Amino Functions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . IV. Carbonyl Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . V. Protection of Phosphoric Esters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . VI. Applications to Biological Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . V

179 180 192 195 202 203

CONTENTS

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Inclueion Complexes of the Cyclomalto-oligoeaccharidee (Cyclodextrina) RONALD J. CLARKE,JOHNH. COATES,AND STEPHENF. LINCOLN

I. Introduction . . . , . , , , . . . . . . . , . . . . . . . . . . , . , , , , . . . . . . . . , . . . . . . . . . . . . . . . 11. Historical Review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111. Formation of Inclusion Complexes . . . . . . . , . . . . . . . . . . . . . . , . . . . . . . . . . . . . . . .

IV. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

205 211 219 249

Hydrolysis and Other Cleavages of Glycosidic Linkages in Polysaccharides CHRISTOPHER J. BIERMANN

I.

11. Liberation of N- and @Linked Carbohydrate Chains . . . . . . . . . . . . . . . . . . . . . . . . . 111.

IV. ............................... V. Formolysis and Acetolysis . v1. Enzymic Hydrolysis . . . . , . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . VII. Reductive Cleavage . .

251 255 256 259 269 270 271

Aqueous, High-Temperature Transformation of Carbohydrates Relative to Utilization of Biomass OLOFTHEANDER AND DAVIDA. NELSON

I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11. Transformation of Monomeric Saccharides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111. Transformation of Polysaccharides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . IV. Carbohydrate Transformation in the Presence of Amino Compounds . . . . . . . . . . . . . V. Carbohydrate Transformation in Chemical Processes, Including Humus Formation . . I

273 275 295 307 323

Addendum to Article 3: References Published after 1986 (Added at Proof Stage) KEVIN

Text

B. HICKS

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Addendum to Article 4 RENECSUKAND BRIGITTEI. GLANZER Text

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Addendum to Article 6 RONALD J. CLARKE,JOHNH. COATES,A N D STEPHEN F. LINCOLN Text . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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AUTHOR INDEX. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . SUBJECTINDEX ..........................................................

337 354

PREFACE l'kaditional chromatographic methods for the separation and purification of carbohydrates of all kinds, ranging from mono- to oligo-saccharides, have permitted many important developments in the carbohydrate field. A major advance that has achieved great utility is high-performance (or so-called highpressure) liquid chromatography. This technique, treated in comprehensive practical detail in the present volume by Kevin B. Hicks (Philadelphia), affords, within an hour, precise analytical and preparative separations of mixtures hitherto separable only with difficulty. The next chapter, by RenC Csuk and Brigitte I. Glinzer (Zhrich), constitutes an extensive treatise on the nuclear magnetic resonance (n.m.r.) spectroscopy of fluorinated monosaccharides [whose early chemistry was surveyed in Vol. 38 (1981) by Anna A. E. Penglis]; the comprehensive data tabulated herein should be especially of value to those working in the field. It continues the coverage, in Advances, of n.m.r. spectroscopy as the key tool for characterization of carbohydrates. It complements articles on the 'H-n.m.r. spectroscopy of carbohydrates by Laurance D. Hall [Vols. 19 (1964) and 29 (1974)], Bruce Coxon [vol. 27 (1972)], and Johannes F. G. Vliegenthart, Lambertus Dorland, and Herman van Halbeek [Vol. 41 (1983)], and on the T-n.m.r. spectroscopy of monosaccharides by Klaus Bock and Christian Pedersen [Vol. 41 (198311, of oligosaccharides by the same authors and Henrik Pedersen [Vol. 42 (1984)], and of polysaccharides by Philip A.J. Gorin in Vol. 38 (1981). Protecting groups remain central to the methodology for synthesis of evermore-complex carbohydrate targets. Herein, Uri Zehavi (Rehovot) discusses a somewhat under-utilized but potentially elegant and useful aspect, namely, that of photosensitive protecting groups capable of selective introduction with accessible reagents and subsequent removal under mild irradiation. The chapter is a useful adjunct to that by Roger W. Binkley on the photochemical reactions of carbohydrates that were adumbrated in Vol. 38 (1981). The next chapter, by Ronald T. Clarke, John H. Coates, and Stephen F. Lincoln (Adelaide) discusses inclusion complexes of the cyclomaltooligosaccharides (cyclodextrins), a unique group of natural cryptands that has attracted great interest within and outside the carbohydrate field in recent years. The article updates the pioneering contribution by Dexter French in Vol. 12 (1957) on these oligosaccharides, then known as the Schardinger dextrins. N o chapters treat widely divergent aspects of the aqueous degradation of carbohydrates. Christopher J. Biermann (Corvallis) discusses aqueous acidic hydrolysis and other cleavages of glycosidic linkages in oligo- and polysaccharides, with specific emphasis on their relation to procedures for determination of chemical structure. In the final chapter, Olof Theander (Uppsala) and David A. Nelson (Richland) provide an informative treatment of the vii

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PREFACE

aqueous, high-temperaturetransformation of starch, cellulose, and other abundant carbohydrates relative to the utilization of biomass as a source of useful chemical feedstocks. This issue pays tribute to two scientists who pioneered the development of carbohydrate chemistry in their respective countries of Japan and Argentina, Tohru Komano (Kyoto) and Naoki Kashimura (Mie) describe the life and work of Konoshin Onodera, and an obituary article on Venancio Deulofeu is contributed by Rosa M. de Lederkremer and Eduardo G. Gros (Buenos Aires).

Kensington. Maryland Columbus, Ohio July, 1988

R. STUART TIPSON DEREKHORTON

Advances in Carbohydrate Chemistry and Biochemistry Volume 46

1902-1984

ADVANCES IN CARBOHYDRATE CHEMISTRY AND BIOCHEMISTRY, VOL. 46

KONOSHIN ONODERA 1910-1983 In the Fall of 1983, Konoshin Onodera, Emeritus Professor of Kyoto University, who had retired from academic activity and lay in bed at his home in Kyoto fighting against nephrosis, received greetings from two carbohydrate chemists. Professor Juji Yoshimura of the Tokyo Institute of Technology conveyed to him the recent activities of the Steering Committee of the International Symposium on Carbohydrate Chemistry, in which he was the national representative from’Japan, having succeeded Dr. Onodera in this position. Professor Susumu Hirase of the Kyoto Institute of Technology informed Dr. Onodera about the successful closing in Sendai of the 6th National Carbohydrate Symposium sponsored by the Japanese Society of Carbohydrate Research that was founded by Dr. Onodera (and, since then, the office which had been maintained by him). Afterwards, on October 6, 1983, to our deep regret, Dr. K. Onodera died of a heart attack. K. Onodera was born on October 5 , 1910, in Tsu City, Japan, a little north of the pearl island in Mie Prefecture, to Sakuemon, his father, and Chiyo, his mother, as the second child of six. His father was an official in the Tsu City office. His family history goes back more than 300 years, to the 16th century, when his ancestors came to Tsu with a princess of a feudal clan from the Sendai district in northeastern Japan who married into another feudal clan family; their house still stands, in the center of Tsu. The Onodera family is famous for its relationship to a historical event which happened on December 14, 1702, the 15th year in the Genroku era. This event was triggered by a group of Ronin soldiers (47 samurai) who lost their clan master. The master was ordered by the Shogun to take the blame for his deed in the shogunate castle, which meant death by hara-kiri. The 47 Ronin took revolutionary action to protest against this decision and to show their devotion to their master, although such an action was prohibited at that time. Junai Onodera was one of the members of the 47 samurai. He sent a letter to his relative, Onodera’s ancestor, asking for care for his soon-to-be bereaved family, because he would surely commit hara-kiri after the event; this letter still remains in Onodera’s house. The event was made into a Kabuki drama, and it has frequently been performed since that time. 1 Copyright 0 1988 by Academic Press, Inc. All rights of reproduction in any form reserved.

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Onodera spent his school days in Tsu. He was an honest and active boy in his childhood. In 1927, when he entered the Dai-san (the Third) High School, his family moved to Kyoto from Tsu. At that time, the State High Schools in Japan were numbered, and Dai-san High School was founded in Kyoto. After World War 11, the educational systems were changed, and the Dai-san High School was reorganized, to become the Department of Liberal Arts and Sciences of Kyoto University. Kyoto had been the capital of Japan for more than 1,000 years, as well as the center of the politics, economy, culture, and religion of Japan, so that, since olden times, many young people have gone to Kyoto to be educated. In March, 1932, Onodera graduated from the Dai-san High School, and he entered Kyoto University in April of the same year. In those days, it usually took 3 years to graduate from High School, but he took 5 , the reason being that he was very interested in mountain climbing. He and his group climbed many mountains throughout Japan, and became the pioneers of modern Japanese mountaineering. He was, indeed, famous as a mountain climber, as well as a carbohydrate chemist, in Japan. Onodera chose the Agricultural Chemistry course in the Faculty of Agriculture when he entered Kyoto University, the reason being that his intimate seniors in the mountaineering club were in the same course! There, he could study biochemistry and applied biochemistry. He chose Protein Chemistry, Carbohydrate Chemistry, Lipid Chemistry, Vitaminology, Nutritional Chemistry, Fermentation and Applied Microbiology, and Agronomical Chemistry (including Soil Sciences and Plant Fertilizers). Agricultural chemistry in Japan is known as the course which provides educational background and research on the nature of the composition of animals, plants, and micro-organisms and of their products, such as, vital substances of foods for human consumption; the functions and transformations of chemical entities in biological and food systems; and the chemical and energetic changes associated with these in the course of the activities of living things during both preharvest and postharvest. During Onodera’s time, one of the main biochemical interests in Japan was the chemistry and biochemistry of polysaccharides as a branch of polymer science. Cellulose, starch, and glycogen were investigated intensively. Onodera chose the Laboratory of Biological Chemistry in which to write his graduation thesis in 1934, the last year of his agricultural chemistry course. Onodera’s professor at that time was Dr. Bunsuke Suzuki, who later became a Professor of the University of Tokyo and was well known as a lipid investigator. Studies on the structure of fibroin, carbohydrate metabolism, separation of triglycerides from animals and plants, an analytic

OBITUARY-KONOSHIN ONODERA

3

method for molecular species of fatty acids, and structures of starch or glycosides were made in his laboratory, as in many other laboratories of biochemistry. Onodera’s baccalaureate graduation thesis was on the saponin components included in the bark of Schima liukiuensis, Nakai. Those who knew him in those days used to say that he worked energetically all day, and even if he got good results, he repeated the same experiment again and again, until he got reproducible data; therefore, his results were truly reliable. Because he was so captivated by the study of biochemistry, his mountaineering activities were now limited to long summer vacations and the winter holidays. In March, 1935, he finished the agricultural chemistry course and, in July of the same year, he was appointed a research assistant in the Laboratory of Biological Chemistry, Department of Agricultural Chemistry, Kyoto University, and took his first step as a research investigator. In 1937, Onodera married Miss Yukari Yamada, who was born to a Shoya (mayor) in Goboh City, Wakayama Prefecture. His first work in the Laboratory of Biological Chemistry was on the purification and properties of potato phosphorylase, but he soon changed his subject to the study of amino-containing sugars. It was not well understood at that time whether there were impurities in the products of separation and purification of proteins. Consequently, Onodera made up his mind to devote his whole life to identifying the chemical nature of aminocontaining sugars. In 1939, Dr. Yoshiyuki Inoue became the Professor of the laboratory when Professor B. Suzuki moved to the University of Tokyo. In March, 1940, Onodera joined Professor Inoue’s group, and continued his work in carbohydrate chemistry. In August, 1949, he received his Ph. D. degree from Kyoto University. The title of his thesis was “Biochemical Studies on Starch, Amino-Containing Sugars, and N-Glycosides” (written in Japanese). Onodera tried to separate amino-containing sugars from proteins, but he was unable to obtain constant results at that time. Then, he started to investigate the chemical reactions of amino-containing sugars, and synthesized some of their derivatives in a chemical process. During World War 11, it had been very difficult for him to continue scientific work on a high level. Even under poor conditions, he accomplished a study on the a,@-transformation of glycosides in cooperation with Drs. I. Karasawa and S. Kitaoka. In May, 1944, Onodera was promoted to Associate Professor. After 1950, the condition of scientific research in Japan gradually improved, and Onodera and his associates succeeded in publishing the following results: deamination of D-glucosamine by barium hypobromite (1952); transgly-

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cosylation of N-glycosides (1953); synthesis of N-glycosides with Brigl’s anhydride (1954); and studies on p-toluidine N-D-fructoside (1954). Studying in Dr. M. L. Wolfrom’s laboratory, Department of Chemistry, The Ohio State University, Columbus, Ohio, strengthened Onodera’s commitment to be a carbohydrate chemist. In August, 1953, he crossed the Pacific Ocean by ship, and took the transcontinental railway to Columbus. He later told about this journey as follows. “The voyage on the S . S . Cleveland was very pleasant. I got acquainted with many persons and had a good time. This experience was quite effective in raising my expectations to be able to work with Dr. M. L. Wolfrom. I knew the United States of America was a big country, and I realized how big it was only after taking the transcontinental railway. ” He investigated the synthesis of dithioacetals of D-glucuronic acid and 2-amino-2-deoxy-~-galactose, and reported the results in the J . Am. Chem. Soc., Vol. 79 (1957). He also had valuable experiences other than research, because he met many world-famous carbohydrate chemists and became friends with them. Later, he used to talk about the good days at Columbus, and wrote in a poem: “Hospitable were people at the sugar alley, Beautiful was spring on the gentle stream, the star above buckeye tree sparkles friendly, To the old street wanders evening dream.” We also remember him often saying that Dr. M. L. Wolfrom had told him to read the experimental sections of scientific papers before the summaries and introductions. In November, 1956, Onodera returned to Kyoto University and engaged in research on carbohydrate chemistry again. The articles he then published were concerned with an acyl migration in acetohalogeno-glucosaminides (1957); N-acetylation of 2-amino-2-deoxy-~-glucosewith mixed carboxylic acid anhydrides (1960); and N-acylation of unsubstituted D-glycosylamines (1960). Many young research investigators and graduate students joined his group, because his new ideas from experiences in America attracted them. In August, 1960, Onodera was appointed Professor of the Laboratory of Biological Chemistry, Department of Agricultural Chemistry, Kyoto University. He further developed carbohydrate chemistry after he became Professor. In the early period, Drs. S. Kitaoka, H. Ochiai, S. Hirano, and T. Komano worked with him. The work accomplished at that time included the following: N-debenzyloxycarbonylation of 1,3,4,6-tetraO-acetyl-2-(benzyloxycarbonyl)amino-2-deoxy-~-hexopyranoses in the conversion of a,@-acetoxy to glycosyl bromide (1961); oxidative cleavages of 1,Zdiamino sugars and their significance in the mechanism of the aminocarbonyl reactions (1962); and synthesis of 2-amin0-2-deoxy-p-~glucosides via 3,4,6-tri-0-acetyl-2-benzylsulfonamido-2-deoxy-a-~-g1ucopyranosyl bromide (1962).

OBITUARY-KONOSHIN ONODERA

5

Soon after he became Professor, he also became the President of the Kyoto University Alpine Club (1961). The first plan that he scheduled was to conquer an unclimbed summit in the Himalayas. Whoever an alpinist might be, he wants to try once to climb Mt. Everest, and that was Onodera’s dream from his youth. He went to the Himalayas as a leader with six members of the club, and was successful in conquering Indrasan and Deo Tibba. The results were published in the Himalayan Journal, 24 (1963) 90-95, entitled “The Ascent of Indrasan and Deo Tibba,” by Onodera. “The expedition organized and sent made the first ascent of Indrasan (6,221 meters) on October 13,1962. The party also climbed Deo Tibba (6,000 meters).” Onodera stayed in the base camp, encouraged the members, and advised them to move carefully. This great achievement had an important effect not only on young students, including members of his Institute, but also on all Japanese youth, especially alpinists. Also in 1967, Onodera went on another expedition, to India and Bhutan, but, unfortunately, this time he was not successful, as he could not get permission to ascend a peak from Bhutan. Onodera used to work in the laboratory from early in the morning to late at night and would discuss research projects with young coworkers. He used to walk around the laboratory several times a day and hear from them how their work was progressing. He discussed with humor the historical background of past work and persons who contributed to carbohydrate research in his laboratory, as well as in foreign institutions. When a graduate student was disappointed that his experiment was hopeless because the derivatives of carbohydrates had not readily crystallized, he gave the student advice and encouragement to be careful and patient. During his professorship, from 1960 to 1974, he accomplished many tasks. We may classify them roughly as follows: development of a synthetic procedure for nucleosides; establishment of a new oxidation method for sugars; chemistry of sugar moieties of glycosaminoglycans, and their chemical structures; and conformations of sugar moieties of some nucleotide analogs, “sugar nucleotides,” and acidic polysaccharides. He summarized these results in a paper entitled “Retrospect and Prospect in Carbohydrate Chemistry and Biochemistry” (Memoirs of the College of Agriculture, Kyoto University, No. 102, Chemical Series No. 33). He described his philosophy and attitudes on biological chemistry in the Preface section of the Memoirs, stating that “The aim of biological chemistry is, I believe, the eventual elucidation of the structure and function of organic substances in biological environment. This line of consideration naturally led us to make efforts to correlate the structure of biopolymers with the function of them. Our topics have all been started with the hope in mind that studies on stereochemistry of substances will

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contribute to the elucidation of their biochemical functions. For this purpose, especially, conformational analysis will become a more and more useful tool in chemistry and biochemistry of carbohydrates.” He continued that “In retrospect, I feel that our research areas were more or less in diversity which resulted in vagueness in a way of standpoint for research objectives. In prospect, I really hope that this issue will be of value for stimulating research in the carbohydrate field in our country.” A brief summary of Onodera’s various fields of research begins with the development of a synthetic procedure for nucleosides. This study was made with Drs. H. Fukumi, F. Masuda, T. Yajima, and other coworkers. He considered that investigation of a synthetic procedure for nucleosides and related compounds would contribute to the chemistry and biochemistry of nucleic acid constituents. At that time, he had already started a series of studies on nucleic acid biochemistry with Dr. T. Komano, who developed the subject further into molecular genetics and gene technology. Onodera first attempted to develop a new procedure in which 1-0(trichloroacety1)ated sugars were used instead of acylated sugar halides, expecting that stereospecific synthesis of an N-glycosylic linkage might be possible. Efforts were also concentrated on the stereospecific synthesis of nucleosides with the use of phosphorus pentaoxide or polyphosphoric acid as a dehydrating agent in solution reactions, or ethyl polyphosphate as a catalyst in fusion methods. The results obtained in improved procedures for fusion methods further developed a new method for the novel synthesis of such 1’,2’-cisnucleosides as a-adenosine, and a novel synthesis of several theophylline nucleoside derivatives having a 2’,3’-unsaturated grouping. A second field concerned oxidation and polymerization of sugars with phosphorus pentaoxide. Drs. S. Hirano, N. Kashimura, N. Miyazaki, and other coworkers cooperated to promote this project. In the course of studying the polymerization reaction of reducing mono- and di-saccharides, they found that dimethyl sulfoxide containing phosphorus pentaoxide rapidly oxidizes the alcoholic groups of sugars at room temperature, to produce aldehydes, ketones, or carboxylic acids. This finding, together with the results of Dr. Albright’s work on dimethyl sulfoxideacetic anhydride as an oxidant, was just on the verge of the coming development of dimethyl sulfoxide-mediated oxidation of alcohols that had been pioneered by Dr. J. G. Moffatt and was followed by a number of new dimethyl sulfoxide oxidants. By using this dimethyl sulfoxide-phosphorus pentaoxide mixture, he succeeded in synthesizing a number of aldosuloses and aldosiduloses in good yields. Among them were 1,2 :5,6di-O-isopropylidene-c~-~-ribo-hexofuranos-3-ulose and methyl 2-acetamido-4,6-O-benzylidene-2-deoxy-c~-~-ribo-hexopyranosid-3-ulose that had not been readily obtained by conventional methods.

OBITUARY-KONOSHIN

ONODERA

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Another field of research concentrated on the chemistry of sugar moieties and chemical structures of glycosaminoglycans. Drs. S. Hirano, H. Hayashi, T. Komano, and other coworkers cooperated in this research. At first, an attempt was made to prepare N-acetylneuraminic acid isomers, in which a product from the reaction of oxaloacetic acid with N-acetyl-D-galactosamine was compared with those from those of oxaloacetic acid with N-acetyl-D-glucosamine and N-acetybmannosamine. At the same time, the distribution of sialic acid in biological materials, mainly of plant origin, was also investigated. 2-Amino-2-deoxy-~hexosides and D-glucosiduronic acids were synthesized, and the behavior of those glycosides on acid hydrolysis was investigated in relation to the isolation of unit hexosaminide disaccharides from glycosaminoglycans. He actually succeeded in isolating a 2-amino-2-deoxy-~-galactosidedisaccharide from chondroitin sulfate C. Infrared spectroscopic analysis was applied to study of the disposition of the sulfuric ester groups, and also to sulfonate groups at positions other than C- 1 on the aldopyranose ring. The methylation of heparin, heparitin sulfate, and oligosaccharides from hyaluronic acid was performed in order to analyze the structures. He also studied the constituents and structures of glycosaminoglycans and glycoproteins in human and cow colostrums. A fourth area of study dealt with the conformations of sugar moieties of some nucleotide analogs, “sugar nucleotides,” and some acidic glycosaminoglycans. This research was conducted with Drs. S. Hirano, N. Kashimura, F. Masuda, and other coworkers. ‘H-Nuclearmagnetic resonance spectroscopy was the main tool for conformational analyses of a number of a-nucleosides and a-glycopyranosidesin various solvents, and led to the finding that some derivatives exist in the so-called alternative chair conformation. He also found that chondroitin has a random conformation. Conformational inversion was shown to occur in the molecule of chondroitin 6-sulfate by additional sulfation on C-4 of the 2-acetamido-2deoxy-D-glucopyranosemoiety, whereas it did not occur in the molecule of chondroitin 4-sulfate by additional sulfation on C-6 of the hexosamine moiety. The linkage position of the sulfate group was considered to be important in establishing the conformation with the aid of hydrogen bonds. The D-hexopyranuronic acid moiety of some acidic glycosaminoglycans adopts the * C ~ ( Dconformation, ) whereas the D-glucopyranuronic acid moiety of UDP-D-glucuronic acid adopts the 4CI(D) conformation. Therefore, he assumed that the conformational inversion of the sugar moiety took place when the glycosyl group was transferred from the glycosyl donor to the acceptor. Onodera mentioned in the last part of the Preface section of the Memoirs as follows: “During compiling of this issue, I have been immersed in a pleasant recollection of past years when many collaborators, to whom I

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TOHRU KOMANO A N D NAOKI KASHIMURA

wish to express many thanks, worked with me in the old,’underequipped laboratory.” In fact, in comparison with the well-equipped laboratory of the Department of Chemistry, Ohio State University, the laboratory he inherited was not in good condition. During World War 11, it was not exceptional for many research investigators to leave their laboratories. Fortunately, Onodera was able to stay in the laboratory and continue his education and research. However, it was almost impossible to obtain sufficient supplies of chemical reagents, experimental materials, and equipment for research. Following the war, it took over ten years for the university to regain full activity. He used to talk reminiscently to younger generations, as he looked back on the days after World War 11: “You have to be patient, even though you can’t get a good experimental result. You should feel happy, because it is a time when no one can prohibit you from research on whatever you wish.” It seemed to us that Onodera was now having difficulties going up and down the stairs when he was over 60. Once he told us that he had slipped on a rock when he was climbing a mountain, and had injured his knee; but he used to come to the laboratory on foot when the weather was fine. As his house was halfway up a small hill on the east side of Kyoto City, there were many historical temples and shrines along the way to it, where beautiful trees and gardens could be seen. It was good for him to walk a distance of about 3 kilometers, looking at the view. In the spring, cherry blossoms were in full bloom and, in autumn, the leaves turned red. He really loved these views in Kyoto, and was also very fond of listening to the music of Mozart and Beethoven in his yard and in his large wooden, typical Japanese-style house. Onodera played an important role on the editorial staffs of both the Agricultural Chemical Society and the Biochemical Society of Japan. In the Agricultural Chemical Society, he acted as Chairman of a branch of the Kansai district (west part of Japan) from 1967 to 1969. He was elected a member of the Science Council of Japan from 1968 to 1971. He was awarded the Suzuki prize by the Agricultural Chemical Society of Japan, the highest award of the Society, for his meritorious deeds in carbohydrate chemistry. But what he felt proudest of, and most honored about, was his appointment to the Editorial Board of Carbohydrate Research for 13 years (from 1966 to 1979). He devoted much energy to the 8th International Symposium on Carbohydrate Chemistry, held in the summer of 1975 in Kyoto. Japanese carbohydrate chemists belonged either to the Agricultural Chemical Society (to which Onodera belonged), the Biochemical Society, the Society of Pharmaceutical Science, or the Chemical Society of Japan. Consequently, the scientific papers, on carbohydrates, from Japan were published in various

OBITUARY-KONOSHIN

ONODERA

9

journals. Onodera thought it was necessary to have an opportunity for Japanese carbohydrate chemists to meet together to discuss the matters that they were concerned with. He was appointed Chairman of the 8th Symposium. He took it on himself to establish the Japanese Society of Carbohydrate Research in Japan. The members who took part in establishment of the Society were Drs. S. Umezawa, N. Iseki, J. Yoshimura, K. Anno, T. Yamakawa, A. Misaki, Z. Yoshizawa, Y. Matsushima, S . Hirase, and many other carbohydrate chemists. The Society now has over 600 members, and held its 8th National Symposium in Kyoto in the summer of 1985. Onodera retired from Kyoto University in April 1974, when he was 63 years old, due to regulations for the retirement of members of the Kyoto University Faculty. After the International Symposium on Carbohydrate Chemistry in Kyoto, his health seemed to be getting worse. But nobody, maybe not even he, recognized that he was suffering from a serious disease. We had all thought him to be in excellent health. Because he was an alpinist, he had confidence in his health, as did we. At the end of 1979, he was moved to a hospital, and he remained there under medical care for about 3 months. Afterwards, he had to visit the hospital twice a week for kidney dialysis. Six months later, fortunately, he recovered markedly enough to be able to talk about the good and happy old days. In the spring of 1983, his condition became worse. On April 29th, 1983, the birthday of the Emperor, Onodera was awarded (and received) a memorial medal by the Japanese Government for his achievements as a Professor of Kyoto University. On this commemorative occasion, more than 120 persons who had been associated with him prepared a present for him in order to express their gratitude; and, of course, he received it while lying in bed. He sleeps on a small hill, in Tsu where he was born; he is survived by Yukari, his wife of 46 years, sons Akifumi and Koji, daughters Mizuyo and Fumi, and numerous friends, including many Japanese carbohydrate chemists.

TOHRUKOMANO NAOKIKASHIMURA

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ADVANCES IN CARBOHYDRATE CHEMISTRY AND BIOCHEMISTRY, VOL. 46

VENANCIO DEULOFEU 1902-1984

Venancio Deulofeu, first son of Tomas Deulofeu and Camila Gascons, was born on April lst, 1902, in Buenos Aires to a high middle-class family. He died in that city on October 4th, 1984. While he was studying in elementary school, his family made a trip to Spain, where they remained for one year before returning to Argentina. Between 1914 and 1919, the young Venancio attended an official secondary school. He also enjoyed playing the piano, but his music studies were set aside when he started his university career at the Facultad de Ciencias Exactas, Fkicas y Naturales of the Universidad de Buenos Aires, pursuing a degree in Chemistry, a speciality not very extended in the Argentina of the beginning of the century. In 1923, while studying for his degree, he was invited by Prof. A. Sordelli to collaborate in investigations on the isolation and purification of bovine insulin which were being performed at the Instituto Bacteriologico. Deulofeu’s stay at this institute influenced his temperament, and aroused his taste for scientific research. He obtained, with honours, his degree in Chemistry in 1924, continuing at his position with Sordelli and publishing his first papers on subjects related to the chemistry of insulin. The work of ZemplCn on the degradation of acetylated aldononitriles inspired Deulofeu to start investigations in the field of carbohydrates, which was virgin at that time in Latin America. In 1929, by degradation of the tetraacetate of L-xylononitrile, he prepared L-threose, and, in a similar way, he obtained L-erythrose from tetra-0-acetyl-L-arabinononitrile. These reactions formed part of his Doctoral Thesis on “Degradation in the Group of the Monoses,” with which he earned a Doctors’ degree in Organic Chemistry in 1930. The first step in the reaction yields “aldose diamides”, usually as crystalline solids, which upon acid hydrolysis afford an aldose with one carbon less than the original nitrile. The mechanism of the ammonolysis of the acylated nitriles intrigued Deulofeu. Experiments carried out with Hockett and Deferrari, employing labelled ammonia, gave the first proof as to the intramolecular nature of the reaction. A review on the degradation of acylated aldononitriles, written by Deulofeu, was published’ in Advances in Carbohydrate Chemistry. He (1) V. Deulofeu, “The Acylated Nitriles of Aldonic Acids and Their Degradation,” Adu. Carbohydr. Chem., 4 (1949) 119-151.

11 Copyright Q 1988 by Academic Press, Inc. All rights of reproduction in any form reserved.

12

ROSA M.

DE

LEDERKREMER AND EDUARDO G. GROS

also found that the 1,l-bis(acy1amido)-1-deoxyalditolsare formed by the action of aqueous or alcoholic ammonia on acylated aldoses. This reaction was systematically extended through the monosaccharide series, and the mechanism for the 0 + N acyl migration was studied by appropriate labelling of the benzoyl groups in the pentabenzoates of D-glucopyranose and D-galactopyranose. From his results, the individual contribution of the acyl groups at the different positions on the chain was established. The contribution of the 2-0-benzoyl group was the lowest, and that for the 4-0-benzoyl group the highest, to afford the corresponding “aldose diamide.” The reaction is very complex, and, by application of chromatographic techniques, cyclic N-acyl-D-aldosylamines were also isolated in most cases. It is interesting that he was self-taught in carbohydrate chemistry, because, at that time, no person in Argentina cultivated this speciality. In 1928, he was married to Irene Escasany, the daughter of a wealthy jeweler, and his companion throughout his life, who passed away one week after Deulofeu. Shortly after his thesis work was accepted, Deulofeu proceeded to the University of Munich, where he worked under Prof. H. Wieland on the structural elucidation of bile acids, a subject that had earned Prof. Wieland the 1927 Nobel prize for Chemistry. Deulofeu’s stay in Germany was interrupted by a call from Prof. B. Houssay, who offered him a position as Assistant Professor of Biological Chemistry at the Facultad de Medicina of the Universidad of Buenos Aires, a position that he held until 1948 as a part-time professor. Deulofeu’s reputation as a leading bio-organic chemist was already established, when, in 1939, he was appointed Professor of Organic Chemistry of the Facultad de Ciencias Exactas y Naturales of the same University. In 1941, invited by the Committee for Interamerican Cultural Relationships, he spent almost one year in the Biochemistry Laboratory, School of Medicine of the St. Louis University, doing research with Prof. E. A. Doisy. For unjustifiable political reasons, he was separated from his professorship in 1952, and accepted the position of Research Director at the private company of E. R. Squibb & Sons, where he remained until 1962. From E. R. Squibb & Sons, he launched a program of grants and fellowships to support biomedical research and to cover the expenses of several graduate students who carried out research in the laboratories of the company. Some of his students at that time have since been appointed to important academic and industrial positions in Argentina and abroad. In 1956, he returned, as Professor of Organic Chemistry, to the University, where he stayed until his retirement in 1968, to become Emeritus Professor thereafter.

OBITUARY-VENANCIO DEULOFEU

13

In 1937, he published, first in collaboration with A. D. Marenzi, and later with A. D. Marenzi and A. 0. M. Stoppani, the book Quimica Biolbgica, which was maintained, and reedited nine times, during the following thirty years, and also translated into Portuguese on two occasions. This book was destined to become the standard reference on its subject for Medicine and Biochemistry students of Latin America. In the chair of Organic Chemistry, besides his extraordinary ability as an organizer, he continued to be active in research. Outside the field of carbohydrates, Deulofeu undertook important investigations in other areas. A series of thirteen publications, starting in 1932, dealt with reactions of amino acids. He also had a long-standing interest in natural products of animal and plant origin, mainly Argentinian plants. About fifty publications, starting in 1939, described his results in this field. He was particularly interested in alkaloids, and in this respect he isolated new bases from Licopodium sururus (saurine and sauroxine), elucidated the structure of y-fagarine from Fagara coco, olivacine and guatambuine from Aspidosperma australe, tubulosine from Pogonopus tubulosus, and the partial structure of ocotein from Ocotea puberula. Pharmacological evaluations were performed on some of the bases isolated; thus, the supposed antimalarial action of a total alkaloid fraction from Pogonopus tubulosus was ruled out. Deulofeu was also concerned with the synthesis of alkaloids. These included D-laudanine, pseudocorydine, and racemic pseudocidamine, which was resolved into its optical isomers. Some of his work in the alkaloid field has been reviewed in a book edited by Manske and Holmes.2 With his italian colleague, G. Marini-Bettolo, he characterized flavonoid glycosides from the ombu (Phytolacca dioica), the big tree of our pampas. One of them, called ombuin, was later synthesized for confirmation of its structure. The plant Zlex paraguariensis, used for making an infusion called mate, very popular in Argentina, Uruguay, Paraguay, and Brazil, was also investigated by Deulofeu. Chlorogenic acids and related compounds were characterized. Studies on the isomerization and lactonization of the acids were performed as an aid to understanding the transformations occurring in the processing of the fresh leaves of the plant. In the field of the components of the venom from toads, he studied the venom of most South American species of the genus Bufo, determining with several coworkers, and also in collaboration with T. Reichstein (University of Basel), their composition in regard to bufadienolides, biogenetic amines, and alkaloid-like compounds. (2) V. Deulofeu, J. H. Comin, and M. J. Vernengo, The Benzylisoquinoline Alkaloids, in R. H. F. Manske and H. L. Holmes (Eds.), The Alkaloids: Chemistry and Physiology, Vol. 10, Academic Press, New York, 1967, pp. 401-461.

14

ROSA M.

DE

LEDERKREMER AND EDUARDO G . GROS

From his time at the Squibb research laboratories, he was interested in the chemistry of antibiotics, and in this area, he elucidated the partial structure of curamycin, an antibiotic produced by Streptomyces curacoi. From curamycin, he isolated and characterized the new natural sugar derivatives D-curacose (4-O-methyl-~-fucose), curacin [4-O-(dichloroisoeverninyl)-2,6-dideoxy-~-arabino-hexose], and curamycose (2,6-di0-methyl-D-mannose). In 1977, he published his last original paper on the structure of a quercetin triglycoside containing D-apiose, isolated from Solanum glaucophylum a plant toxic to cattle. In spite of this, his extraordinary capacity as a reader allowed him to remain up to date in a great variety of topics, not only in those of direct interest to him but in those that were studied by several graduate students working under different supervisors. Among the numerous distinctions that Deulofeu received from Argentina and foreign countries, it seems relevant to mention: Doctor Honoris causa, University of Paris; Honorary Professor, University of Chile; Honorary Professor, University of San Marcos (Peru); elected Member of: Academy of Medicine (Argentina); Academy of Exact, Physical, and Natural Sciences (Argentina); Academy of Exact, Physical, and Natural Sciences (Madrid, Spain); Academy of Sciences (Rio de Janeiro, Brazil); and Academy of Arts and Sciences (Barcelona, Spain). He was also an Honorary Member of various Chemical Societies including those of Argentina, Peru, Colombia, Brazil, Chile, Uruguay, Venezuela, Mexico, Spain, and Switzerland. He was the recipient of several awards from Argentinian and international institutions, such as the Prize “Dr. B. A. Houssay” from the Organization of American States (Washington, D.C.) and a Medal from The International Academy of Lutece (France). Deulofeu was a member of the Editorial Board of several scientific publications, including Medicina, Enzymologia, Anales Asociacibn Quimica Argentina, Tetrahedron, Tetrahedron Letters, Index Chemicus, and Carbohydrate Research, and a member of the Assessor Committee of the Editorial Board of Pure and Applied Chemistry. He liked to travel, and he undertook numerous lecture and scientific meeting tours to several American and European countries, and also to the USSR, Japan, and Australia. Deulofeu was a very social gentleman who enjoyed giving parties for many friends and colleagues from foreign countries; on those occasions, he was very proud to show his collection of “mat6s” (the containers for making the infusion already mentioned) made of sterling silver. Short in stature, but robust in appearance, he projected a vitality and animated interest that made him the central focus of scientific gatherings. A special issue of the journal Carbohydrate Research with contribu-

OBITUARY-VENANCIO DEULOFEU

15

tions from friends and former students was published in February, 1973, in honour of Prof. Deulofeu on the seventieth anniversary of his birth. We hope that this short review of Deulofeu’s scientific activities transmits the feeling that his name is almost synonymous with Organic Chemistry in Argentina. ROSAM. DE LEDERKREMER AND EDUARDO G. GROS Departamento de Quimica Orgdnica Facultad de Ciencias Exactas y Naturales Universidad de Buenos Aires Buenos Aires, Argentina

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ADVANCES IN CARBOHYDRATE CHEMISTRY AND BIOCHEMISTRY. VOL. 46

HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY OF CARBOHYDRATES BY KEVINB. HICKS Eastern Regional Research Center, Agricultural Research Service, U.S. Department of Agriculture, Philadelphia, Pennsylvania 19118

I. Introduction ............................................ ;. ............. 11. Instrumentation and Stationary Phases. ................................... 1. Chromatographic Equipment. ......................................... 2. Stationary Phases.. .................................................. 111. Separations and Applications. ............................................ 1. Analytical Separations ................................................ 2. Additional, Selected Applications ...................................... 3. Preparative, Liquid Chromatography ................................... IV. Special Aspects and Problems.. .......................................... 1. Detectability and Accuracy. ........................................... 2. Combined L.C. Techniques (L.C.-M.S., and L.C.-N.M.R. Spectroscopy) 3. Separation of Carbohydrate Anomers. .................................. 4. Future Trends ....................................................... Addendum: References Since 1986 .......................................

.

17 18 18 23 32 32 50 58 63 63 69 70 71 327

I. INTRODUCTION

This chapter covers advances in so-called high-pressure or high-performance liquid chromatography (often abbreviated as h.p.1.c.) of carbohydrates. The term 1.c. is used here to designate the rapid (30 MPa. In this chapter, 1.c. separations of almost all mono-, di-, and oligosaccharides are discussed from both a theoretical and a practical point of view. In addition, the general principles involved in the care and mainte17

18

KEVIN B. HICKS

nance of the relevant instrumentation and stationary phases are covered. A separate Section on preparative 1.c. methods for carbohydrates has been included, and this is the first article to treat this important and growing subject. Other Sections, which provide solutions to problems of detectability and of peak broadening (resolution of anomeric forms) are included, and the current status of emerging 1.c. techniques (1.c.-m.s., and high-performance affinity chromatography) are considered. High-performance, size-exclusion chromatography of oligo- and poly-saccharides will not be discussed here, but it has been described in two reviews.*J It is assumed that the reader is familiar with such common chromatographic concepts as efficiency, selectivity, capacity factors, and theoretical plates, and how these parameters affect and effect chromatographic resolution. Excellent descriptions of these general chromatographic principles have been p ~ b l i s h e d .Other ~ . ~ reviews on various aspects of carbohydrate separations will be cited in the appropriate Sections. 11. INSTRUMENTATION* AND STATIONARY PHASES 1. Chromatographic Equipment

a. Solvent-delivery Systems.-Almost all modern, commercially available pumps and controllers are useful for this kind of carbohydrate analysis. Some, however, because of aspects specifically related to carbohydrate applications, are more useful than others. A majority of the 1.c. methods described here required refractive-index detectors, and these instruments are sensitive to changes in solvent flow, pressure, and composition. Hence, the most useful pumping systems are those that deliver pulse-free and precise solvent-flow. Although most solvent-delivery systems are capable of blending two or more solvents, to afford isocratic mobile phases, few of these systems can blend these solvents accurately, and when the columns on these systems are monitored by refractive index detectors, extremely unstable baselines are the result. Hence, many chromatographers must tediously pre-mix their solvents in order to obtain (1) S. C. Churms, in E. Heftman (Ed.), J . Chromatogr. Library, Elsevier, New York, 1983, pp. B223-B286. (2) S. C. Churms, in G . Zweig and J. Sherma (Eds.), Handbook ofChromatography, Carbohydrates, Vol. I, CRC Press, Boca Raton, FL, 1982, pp. 69-129 and 175-187. (3) K.-P. Hupe, in A. Henschen, K.-P. Hupe, F . Lottspeich, and W. Voelter (Eds.), High Pe$ormance Liquid Chromatography in Biochemistry, VCH Publishers, Deerfield Beach, FL, 1985, pp. 1-15. (4) L. R. Snyder and J. J. Kirkland, Introduction fo Modern Liquid Chromatography, 2nd edn., Wiley-Interscience, New York, 1979, pp. 15-82. * Reference to a brand or firm name does not constitute endorsement by the U.S. Department of Agriculture over others of a similar nature not mentioned.

H.P.L.C. OF CARBOHYDRATES

19

stable baselines. Some pumps are now available that are capable of accurately mixing solvents on line, and the purchase of these instruments is recommended. Another consideration in choosing a solvent-delivery system is the matter of the maximum and minimum flow-rate ranges. For extremely precise solvent-metering in microbore-column applications, pumps capable of operating in the 50-100 pL/min range are useful. For preparative chromatography, “dedicated” preparative instrument^^.^ are available that can provide flow rates in excess of 100 mL/min. For most laboratory applications, however, it is not necessary to buy a dedicated microbore or pre~ * ~are caparative chromatograph, as 1.c. systems are now a ~ a i l a b l ethat pable of-performing both functions with only minor changes in plumbing and hardware. Regardless of the type of solvent-delivery system used, solvents should, for best results, be degassed by vacuum, with helium, or by use of commercial degassing instruments. All of these degassing systems work well, but the last is the most convenient, and allows continuous operation. b. Equipment for Preserving Column-Life.-Equipment in this category includes pre-columns, guard columns, silica saturator9J0 columns, and various cartridges containing bonded-phase packings or ion-exchange resins. These can, and should, be used on- or off-line, to prevent sample contaminants from entering the analytical column. The appropriate use of saturator and pre-columns for each type of column stationary-phase will be given in the next Section. When pre-columns are installed instead of sample loops, they can be used as concentratorsI1 for dilute samples, and can be readily backflushed, after injection, to remove unwanted samplecomponents. l 2 Bonded-phase silica and ion-exchange resins in plastic cartridges and mini-columns are very useful for off-line prepurification of samples, especially those for preparative chromatography, when appropriate pre- or guard columns may not be available for on-line clean-up of a sample. (5) N. W. H. Cheetham and P. Sirimanne, Carbohydr. Res., 96 (1981) 126-128. (6) C. D. Warren, A. S. Schmit, and R. W. Jeanloz, Carbohydr. Res., 116 (1983) 171182. (7) K. B. Hicks, S. M. Sondey, D. Hargrave, G . M. Sapers, and A. Bilyk, LC Mag., 3 (1985) 981-984. (8) K. B. Hicks and S. M. Sondey, J . Chrornarogr., 389 (1987) 183-194. (9) D. L. Hendrix, R. E. Lee, Jr., J. G . Baust, and H. James, J . Chromarogr., 210 (1981) 45-53. (10) B. Porsch, J . Chrornatogr., 253 (1982) 49-54. (11) J. A. Polta, D. C. Johnson, and K . E. Merkel, J . Chrornatogr., 324 (1985) 407-414. (12) K. Mopper and L. Johnson, J . Chrornatogr., 256 (1983) 27-38.

KEVIN B. HICKS

20

These have been effectively used to remove lignin13 and hydrophobic metabolite^'^ from plant-derived samples. Bonded-phase mini-columns are also ideal for the prechromatographic purification of a perbenzoylated sugars,15glycopeptides (and derived oligosaccharides),16and peralkylated oligosaccharides.17,18 c. Switching Valves, Fittings, and Filters.-The creative use of switching valves can save chromatographic-run time and extend column life. They can allow elution of the analytical column while the pre-column is being simultaneously cleaned.'* In chromatograms where they are both very early, and very late peaks, such as those of reducing sugars and their degradation products (for example, furfural~),'~ the use of switching valves can lessen the run time by 50 to 70%. The myriad types of 1.c. fittings produced by a great number of vendors have led to confusion among chromatographers about the proper choice for each application. Fortunately, fittings that are more universal in their applications are now available, and one of the most useful of these has a knurled flange on the nut, and a replaceable, polymeric ferrule. These fittings may be sealed by hand and re-used many times without failure. The use of in-line filters between injectors and column can prevent the accumulation of particulate material on the inlet frit of an analytical column, and can avoid back-pressure problems. A second, and often overlooked, site for filter installation is between the column and the detector. Cartridge-type filtration-units that contain readily changed, 0.2-pm filters are commercially available, and they contribute insignificantly to peak broadening. These filters are essential for the prevention of clogged detectors when laboratory-packed columns are used.

d. Injectors.-The choice of injector depends upon the particular application, namely, analytical or preparative chromatography. For the former, fixed-loop injectors are far more accurate than the partially filled loop (universal injector) design. For occasional analytical and preparative G . Bonn, R. Pecina, E. Burtscher, and 0. Bobleter, J . Chromatogr., 287 (1984) 215221.

R. Schwarzenbach, J . Chromatogr., 140 (1977) 304-309. P. W. Tang and J. M. Williams, Anal. Biochem., 142 (1984) 37-42. S. J. Swiedler, J. H. Freed, A. L. Tarentino, T. H. Plummer, Jr., and G . W. Hart, J . Biol. Chem., 260 (1985) 4046-4054. M. W. Spellman, M. McNeil, A. G . Darvill, P. Albersheim, and A. Dell, Carbohydr. Res., 122 (1983) 131-153. J. M. Lau, M. McNeil, A. G . Darvill, and P. Albersheim, Carbohydr. Res.; 137 (1985) 111-125.

D. W. Patrick and W. R. Kracht, J . Chrornatogr., 318 (1985) 269-278.

H.P.L.C. OF CARBOHYDRATES

21

applications, the universal design is useful, because any volume up to a few mL may be injected. For automated, or manual, preparative injection, fixed-loop injectors may be used with large loop sizes (up to 10 or 20 mL) that are currently available. Custom loops are also readily made with 0.5 mm (0.020”) or 0.75 mm (0.030) (i.d.) tubing, cut to the appropriate length. e. Column Design.-Because the heart of any chromatographic system is the column, considerable attention has been devoted to improvements, through new designs, in its efficiency and stability. The 10-pm packings and 25-cm-long columns of the 1970’s have given way to the 5-pm (15 cm) and 3-pm (10 cm) columns available today. These improvements have resulted in faster, higher resolution, and more-sensitive separations and analyses. Although most columns are of the traditional, steel-tube-withend-fittings design, newer columns are available as cartridges with reusable end-fittings. Such cartridges that fit into dynamic axial compression fittingss or radial compression modules20.21 are especially useful, because voids that develop in the stationary phase are removed by the changing configuration of the module. The diameter of commercial, 1.c. columns is also evolving toward wider bores. Initial reports that only long, narrow columns (10 mL/min). One commercially available8refractive-index monitor can be used at flow rates of up to 100 mL/min, but it is equally useful for analytical work at 320 nm to the reducing sugars in very high yields (compare Scheme 7 for an example, and Scheme 3 for a proposed mechaSoon after the introduction of the aforementioned glycosides, a lightsensitive polymer (a modified, cross-linked polystyrene) was synthesized, and it served as the aglycon in developing a polymer-supported, oligosaccharide synthesis.20At the end of the synthesis, a benzylated disaccharide was removed from the polymer by photolysis at >320 nm in very high yield (see Scheme 8), and hydrogenolyzed to isomaltose. The 2-nitrobenzyl linkage between the saccharide derivatives and the polymer provided a stable “hook” during synthesis, and the end product was a free, reducing sugar. Subsequently, a combined organic-enzymic approach was proposed5 for the synthesis of oligosaccharides. By common organic procedures, a (29) U. Zehavi, B. Amit, and A. Patchornik, J . Org. Chem., 37 (1972) 2281-2285. (30) U. Zehavi and A. Patchornik, J . Org. Chem., 37 (1972) 2285-2288.

DCN

hv

'OCN*

CH,OH

+

QPh HO

?

-

'OCN*

+

OCN'

OH

OH

1

I"+

MeOH,-H*

CHzOH HOQMe

+

CH20H

HoQoMe

OH 36 '1.

H

O

G

OH

49 'I. SCHEME 6.-Proposed Mechanism for the Photoinduced, Electron-transfer Reaction of Phenyl p-D-Glucypyranoside with 1.4-Dicyanonaphthalene (DCN) in 1 : 10 Methanol-Acetonitrile. Irradiation at 350 nm was Continued for 72 h.

OMe

OH OMe

CH20H HOO

O

H

+ ocH+OMe

ON OH SCHEME 7.-Photochemical Cleavage of 6-Nitroveratryl p-D-Glucopyranoside.

@I

@I

0

~N@COocH2

, ++oe :

Oeacylation C A 6tta H 6ch , C5H5N ment

NO2

*

HOCH2

OBn

2

1

~

0nO QOCH?

NO2

OBn

NaOEt

OBn

3

4

@I

I

.

Deacylation Elongation

1 + 4

NaOEt

NO2

C ~ H GCsHgN , OBn

OBn

6

5

ooH . @I

6

Release hv c

OBn

NO

en0

H2,PdlC

OH

CHO

OH

OBn

lsomaltose

7

8

SCHEME8.--Synthesis of Isomaltose (8) on a Light-sensitive, Solid Support (@).

PHOTOSENSITIVE PROTECTING GROUPS

187

saccharide derivative is attached, by way of a 2-nitrobenzyl bond, to a polymer where it subsequently serves as an acceptor for glycosyltransferase or transglycosylation reaction^.^'-^^ The nature of the newly formed glycosidic bonds is determined by the enzyme specificity, wherever possible, avoiding, among other things, the complex blocking-group chemistry needed for equivalent chemical synthesis. Irradiation at >320 nm releases from the polymer, whether insoluble or water-soluble, free oligosaccharides in very high yields. A simple illustration of such a sequence carried out with either insoluble 2-aminoethylsubstituted poly(acry1amide) beads3' or with water-soluble, substituted poly(viny1 alcohol)32is presented in Scheme 9; the isolated overall yield of lactose was 29.9% (soluble-polymer approach). The synthesis on lightsensitive polymers facilitates the isolation of products, which is important from the preparative point of view and as a tool for the study of enzymes, permitting efficient comparison of acceptor specificity and being capable of demonstrating de nouo synthesis.

90 . CONH-@

HOCHz

+NO?

+

-

HOCH,

UCHZ it;'

HO

OH

H~N-@

HO

OH

UDP-Ga, D-Galaclosykansferase

~

H2

HOCH, O

HOCHl

~ONH@ O

H

+ CHO

I

OH

SCHEME 9.-Incorporation of D-Galactose into a P-D-Glucopyranosyl Polymer Catalyzed by P-D-Galactosyltransferase (EC 2.4.1.22), Followed by Photochemical Release of Lactose.

(31) U. Zehavi, S. Sadeh, and M. Herchman, Carbohydr. Res., 124 (1983) 23-34. (32) U . Zehavi and M. Herchman, Carbohydr. Res., 128 (1984) 160-164. (33) U . Zehavi and M. Herchman, Carbohydr. Res., 151 (1986) 371-378.

URI ZEHAVI

188

b. Protection of Diols.-2-Nitrobenzylidene derivatives of carbohydrates served in the protection of diols and were photolyzed in the pioneering work of T i W i ~ e s c u . ' Isolation ?~~ and characterization of these derivatives and of their photochemical products were hampered, however, by the inadequate physical techniques available at that time. Subsequently, Collins and his collaborator^^^-^^ developed use of the substituent group as an attractive alternative to benzylidene in the selective protection of glycosides (see Scheme lo).

R'

R5°-co9

R3

H u 4 OH

ON

SCHEME10.-Photochemical Cleavage of 2-Nitrobenzylidene Derivatives.

The preparation of 2-nitrobenzylidene derivatives creates a complication, because, in every case, diastereoisomers (endo and exo) are formed. Irradiation at >290 nm of a mixture of the endo and exo isomers leads to results identical to those from the irradiation of the separate isomers, and, in order to facilitate the isolation and characterization of the photoproducts, the aromatic nitroso groups are further oxidized to the corresponding nitro groups with peroxytrifluoroacetic acid (see Scheme 11). The mechanism proposed for the photochemical reaction is analogous to that discussed in the context of nBn ethers and glycosides (see Scheme 3). However, as only, one 2-nitrobenzylidene group protects two hydroxyl groups, the possibility of regiospecificity occurs in the photochemical

(34) I. TBnBsescu, Bull. Soc. Sci. Cluj, 2 (1924) 1 1 1 ; Chem. A s f r . , 19 (1925) 2932. (35) P. M. Collins and N . N. Oparaeche, J . Chem. Soc., Chem. Commun., (1972) 532-533. (36) P. M. Collins and N . N . Oparaeche, Curbohydr. Res., 33 (1974) 35-46. (37) P. M. Collins and N. N. Oparaeche,J. Chem. Soc., Perkin Trans. I , (1975) 1695-1700. (38) P. M. Collins, N. N . Oparaeche, and V . R . N. Munsinghe, J . Chem. Soc., Perkin Trans. I, (1975) 1700-1706. (39) P. M. Collins and V. R. N . Munsinghe, J . Chem. Soc., Chem. Commun., (1981) 362363.

PHOTOSENSITIVE PROTECTING GROUPS

I89

cleavage. In fact, since a nitrosobenzoate is apparently an intermediate, the hydroxy ester, in which the hydroxyl group is equatorial, is preponderant whenever the orthoester is derived from a vicinal diol on a sixmembered ring. The overall yields in the photochemical reaction (followed by oxidation) are normally very high and often even quantitative. Such groups as acetate, nitrobenzoate, methyl glycoside, anhydro, and ptoluenesulfonate are unaffected by the reaction condition^.^^ 2-Nitrobenzylidene derivatives were successfully utilized in syntheses leading to trisaccharides of biological ~ignificance.~~ OMP

OMe

OMe

SCHEME 1 1 .-Utilization of a 2-Nitrobenzylidene Protecting Group in the Synthesis of Methyl 6-Deoxy-2,3-di-0-~-~-galactopyranosyl-c~-~-galactopyranoside. P-D-Galactopyranosyl (R') Substituents Were Introduced by Koenigs-Knorr Syntheses, and the Photochemical Cleavage, at 350 nm, of the 2-Nitrobenzylidene Groups Proceeded Regiospecifically , Yielding, Following Oxidation, a 95% Yield of the 3-Hydroxy-4-(2-nitrobenzoate) Derivative.

The conversion of benzylidene and ethylidene derivatives into hydroxy benzoates and hydroxy acetates, respectively, following irradiation in acetone, and preferably in the presence of oxygen, was discussed by B i n k l e ~Irradiation .~ is carried out at a shorter wavelength (compared to 2-nitrobenzylidene derivatives) and the yields are significantly lower. 3. Protection as Esters Dimethylthiocarbamates are known to undergo photochemical cleavage, leading, in the case of monosaccharide derivatives, to deoxy sugars and to free alcohols (see Scheme 12).637

URI ZEHAVI

I

MeOH

ROH

SCHEME 12.-Proposed Mechanism for the Photochemical Cleavage of Dimethylthiocarbamates (R’ = NMe2, Routes a and b) and xanthates (R1 = SMe, Route a).

In the particular case of 6-O-(dimethylthiocarbamoyl)-1,2:3,4-di-O-isopropylidene-a-D-galactopyranose, the reported yields of the 6-deoxy and the 6-hydroxy products were 25 and 35%, respectively (see Scheme 13). Xanthates, on the other hand, are photolyzed to yield the corresponding alcohols, and the yield reported, for instance for 1,2:3,4-di-O-isopropylidene-6-O-[(methylthio)thiocarbamoyl]-a-~-galactopyranose (50%, see Scheme 13) is apparently lowered by partial removal of isopropylidene groups under the reaction condition^.^^ Photosensitive, 2-nitrobenzylcarbonate was utilized as a hydroxyl-pro-

9 10

R = OCS- NMe2 R = OH

11 R = H

12

R =OCS-SMe

9

L 10 t 11

12

hv

10

SCHEME13.-Photochemical Cleavage of 6-O-(Dimethylthiocarbamoyl)-l,2 : 3,4-di-0isopropylidene-a-D-galactopyranose(9) and of 1,2 : 3,4-Di-O-isopropylidene-6-O-[(methylthio)thiocarbonyl]-a-D-galactopyranose(U). (40) G . Descotes, A. Faure, B. Kyrczka, and M. N . Bouchu, Bull. Acad. Pol. Sci. Chem., 27 (1979) 173-179.

PHOTOSENSITIVE PROTECTING GROUPS

191

tecting group in penicillin ~hemistry.~' The protecting group is probably removed by a mechanism analogous to that proposed for photocleavage of 2-nitrobenzyl ethers (see Scheme 3), releasing the free alcohol, carbon dioxide, and 2-nitrosobenzaldehyde that undergoes further reactions (see Scheme 14). Ro-CO~CH,

9hv

ROH

+

CO2

+

OCH

4N

ON

SCHEME 14.-Photochemical

Cleavage of 2-Nitrobenzylcarbonates.

p-Toluenesulfonates are photolyzed at 94% (43) A. Fox, S . L. Morgan, J. R. Hudson, Z. T. Zhu, and P. Y. Lau, J . Chrornatogr., 256 (1983) 429-438. (44) W . Niedermeier and M. Tomana, Anal. Biochern., 57 (1974) 363-368. (45) R. Kannan, P. N . Seng, and H. Debuch, J . Chrornatogr., 92 (1974) 95-103.

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in all cases. Torello and coworkers22used M hydrochloric acid for 1 to 16 h at 100"for the hydrolysis of human cerebral-cortex ganglioside, GM, ; the highest yield of galactose was obtained after 4 h, whereas the highest yield of glucose and GlcNAc was obtained after 12 h. There was appreciable degradation of the liberated monosaccharides under these conditions, although purging the tubes with nitrogen (instead of air) did not significantly affect the yields. By using correction factors, corrected ratios of monosaccharides in various gangliosides were within 10-20% of the theoretical value. Alpenfels and coworkers46studied the hydrolysis of glycoproteins and keratin fibers with I or 2 M hydrochloric acid for various periods of time at 100".These investigators found that the concentration of neutral monosaccharides from hard keratin reached a maximum after hydrolysis with 2 M hydrochloric acid for 2 h at loo", and the yield of the neutral monosaccharides was linear up to 25 mg of hair per mL of hydrochloric acid solution. The latter fact shows that a relatively large amount of protein does not interfere with the analysis of a relatively small amount of carbohydrate. Griggs and coworkersz3studied the hydrolysis of canine submaxillary mucin (CSM) by 0.5, 3, and 6 M hydrochloric acid for 1.5, 3, 4.5, 6, and 24 h at 100". They found that use of 3 M hydrochloric acid for 3 h gives the maximal release of neutral and amino monosaccharides, with the minimal degradation of the monosaccharides liberated, although recoveries of neutral monosaccharides were only 76-88%. Guen-ant and Moss4' also used hydrolysis with 3 M hydrochloric acid, although for 16 h at 75", for the hydrolysis of bacterial cell-walls. Honda and coworkers25used 4 M hydrochloric acid for 6 h at 100" for the hydrolysis of nondialyzable glycoconjugates when determining amino monosaccharides, but preferred 2 M CF3C02Hfor 6 h at 100"when determining the neutral monosaccharides and uronic acids, as these compounds are subject to more-severe degradation by 4 M hydrochloric acid. They obtained complete hydrolysis (with >90% recovery of monosaccharides added prior to hydrolysis) by using these two sets of hydrolytic conditions. c. Trifluoroacetic Acid.-The use of 2 M CF3C02H by Honda and coworkersz5was discussed in Section IV,3,b. Eggert and Jones4*used 2 M (46) W. F. Alpenfels, R. A. Mathews, D. E. Madden, and A. E. Newsom, J . Liy. Chromatogr., 5 (1982) 1711-1723. (47) G . 0. Guerrant and C. W. Moss, Anal. Chem., 56 (1984) 633-638. (48) F. M. Eggert and M. Jones, J . Chromatogr., 333 (1985) 123-131.

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CHRISTOPHER J. BIERMANN

CF3C02Hfor various lengths of time at 105"for the hydrolysis of neutral sugars in glycoproteins. They found 6-10 h of hydrolysis to be ideal for such glycoproteins as proteodermatan sulfate, salivary glycoproteins, and alpha- 1-acid glycoprotein, whereas 4 h of hydrolysis was sufficient for ovalbumin and fetuin; from this, they recommended 8 h of hydrolysis for unknown glycoproteins and, ideally, a 6-, 8-, and 10-h time-course hydrolysis. They also found hydrolysis with CF3C02H to be superior to that with 2 M hydrochloric acid at 105", owing to the decomposition of liberated monosaccharides by hydrochloric acid. Neutralization of the hydrochloric acid after hydrolysis, but prior to freeze-drying, lessened the decomposition somewhat, although there was still more decomposition than in hydrolysis with CF3C02H. 4 M CF3C02Hfor 1 h at 121" for Neeser and S ~ h w e i z e introduced r~~ hydrolysis of glycoproteins. Both neutral and amino sugars were considered. They compared this method to hydrolysis with 0.6 M hydrochloric acid for 4 h at 100" and 3 M hydrochloric acid for 0.75 h at 125". Hydrolysis of fetal-calf-serum fetuin, bovine submaxillary mucin, and horse-radish peroxidase showed hydrolysis with CF3C02H to be superior. d. Other Methods.-Takemoto and coworkers49 used a mixture of equal amounts of 4 M CF3C02Hand 4 M hydrochloric acid for 6 h at 100" for measurement of the neutral and amino monosaccharides of glycoconjugates. Their rationale was that 2.5 M CF3C02H for 4 h at 100" is useful for measurement of the neutral sugars, but not severe enough for the liberation of amino sugars (especially Asp-GlcNAc) from glycoproteins, whereas hydrolysis with 4 M hydrochloric acid for 6 h at 100" is sufficient to release amino sugars from glycoproteins, but decomposes neutral sugars. The authors found that, with their method, amino sugars were completely liberated, even from Asn-GlcNAc, with no decomposition of glucosamine. Neutral sugars were completely liberated, but underwent some decomposition. Correction factors were applied. This method was applied to alpha- 1-acid glycoprotein, submaxillary-gland mucin, and bovine-brain gangliosides. Some investigators have used an ion-exchange resin in the acid form plus a small proportion of acid to hydrolyze g l y c o p r ~ t e i n s . ~ ~ ~ ~ ~ Lehnhardt and WinzlerS0used 0.1-3.0 mg of glycoprotein with 100 p L of a 20% suspension of Dowex 50 X-2 (H+)ion-exchange resin (200-400 mesh) in 0.02 M hydrochloric acid for up to 40 h on a steam bath. This (49) H. Takemoto, S. Hase, and T. Ikenaka, Anal. Biochem., 145 (1985) 245-250. (50) W. F. Lehnhardt and R. J. Winzler, J . Chromatogr., 34 (1968) 471-479. (51) W. H. Porter, Anal. Biochem., 63 (1975) 27-43.

CLEAVAGES OF POLYSACCHARIDE GLYCOSIDIC LINKAGES

269

method, compared to hydrolysis with 0.5 M H2S04 on a steam bath gave much less decomposition of the neutral monosaccharides liberated from orosomucoid. Because mannose was liberated much more slowly than galactose or fucose in both methods, there was some decomposition of them in the case of hydrolysis with sulfuric acid before all of the mannose had been liberated. Hydrolysis with the ion-exchange resin gave complete hydrolysis after 20 h, whereas hydrolysis with sulfuric acid gave complete hydrolysis after 10 h. Porters1 also used this method of hydrolysis with resin in his study of neutral and amino sugars of alpha-1-acid-glycoprotein and bovine luteinizing hormone. 4. D-Fructans

Polymers of D-fructose are important carbohydrate reserves in a number of plants. Inulins and levans are two major types that differ in structure. D-Fructans require only relatively mild conditions for their hydrolysis, for example, levan was qualitatively hydrolyzed5Ia by hot, dilute, aqueous oxalic acid. Permethylated fructans could be hydrolyzeds2 with 2 M CF3C02H for 30 min at 60". Fructan oligosaccharides were hydrolyzed in dilute sulfuric acid (pH 2) at 70" (see Ref. 53) ors4 95" (0.1 M). D-Fructans from timothy haplocorm (where they comprise 63% of the water-soluble carbohydrates) could be hydrolyzeds5 with 0.01 M hydrochloric acid at 98".

V. FORMOLYSIS A N D ACETOLYSIS Formolysis and acetolysis are not common methods for cleavage of glycosidic linkages. They do have some unique applications, however. For instance, methylated polysaccharides are not generally soluble in hot water, and consequently, hydrolysis is best preceded by formolysis under these circumstance^.'^ For example,565 mg of methylated polysaccharide is dissolved in 3 mL of 90%formic acid, and the solution is kept for 2 h at 100". The formic acid is removed by evaporation at 40". The residue is dissolved in 1 mL of 250 mM sulfuric acid and the solution is heated for 12 h at loo", cooled, the acid neutralized with barium carbonate, the (5la) H . Hibbert and R. S. Tipson, J . Am. Chem. Soc., 52 (1930) 2582; H. Hibbert, R. S. Tipson, and F. Brauns, Can. J . Res., 4 (1931) 221-239. (52) C. J. Pollock, M. A. Hall, and D. P. Roberts, J . Chromatogr., 171 (1979) 411-415. (53) A. Heyraud, M. Rinaudo, and F. R. Taravel, Carbohydr. Res., 128 (1984) 311-320. (54) D. D. Wolf and T. L. Ellmore, Crop Sci., 15 (1975) 775-777. (55) M. B. Suzuki, Cun. J . Bor., 46 (1968) 1201-1206. (56) B. Lindberg, Merhods Enzymol., 28 (1972) 178-195.

210

CHRISTOPHER J. BIERMANN

suspension filtered, and the filtrate concentrated by evaporation at 40" The formolysis procedure has also been used in the study of gangliosides .49 Acetolysis (using sulfuric acid as a catalyst) with 10 : 10 : 1 acetic anhydride-acetic acid-sulfuric acid for 2-13 h at 40" has been used for selective cleavage of glycosidic linkages in yeast mannan~.~' Selective cleavage of (1 + 6) linkages resulted in mixtures of relatively stable, acetylated oligosaccharides containing (1 + 2) and (1 + 3) linkages. The composition of the oligosaccharide mixture is characteristic of the strain of yeast that is the source of the mannan. Acetolysis (using acetic anhydride and sulfuric acid) has also been employed to form the acetates of cellobiose, cellotriose, and higher cello-oligosaccharides from cellulose, but this reaction is not an analytical method.j8 The applications of acetolysis and of formolysis for hydrolysis of glycopeptides have been compared.59 Both methods, used together, were recommended for analysis of samples containing both neutral and aminodeoxyhexitols.

HYDROLYSIS VI. ENZYMIC Enzymic hydrolysis is a useful tool for the identification of carbohydrate linkages,sc as well as for hydrolysis of the (labile) sialic acids.8 Neesefl developed a method wherein the sialic acids are enzymically hydrolyzed and, simultaneously, enzymically converted into stable 2-amino-2-deoxymannose derivatives. This allows determination of carbohydrate constituents of glycoproteins in a single flask. A number of selective glycosidases are now commercially available (see, for example, Ref. 6). For glycoconjugates containing oligosaccharides that are not released under alkaline conditions, enzymic liberation is possible; the details have been given.5cThe fundamental approach is as follows. Proteolytic digestion is first used, followed by gel filtration to separate the oligosaccharides from the free amino acids and short peptides. Exo-glycosidases may then be used to hydrolyze terminal sugar units from the oligo- or poly-saccharides, in order to elucidate the structure. It is important that the enzymes be pure, so that erroneous results For relatively are not obtained; this had been a problem in the simple oligosaccharides, the use of a few exo-glycosidases soon leaves a compound composed of a single monosaccharide linked to an amino acid or short peptide; this constitutes the carbohydrate-peptide linkage. For (57) T. S. Stewart and C. E. Ballou, Biochemistry, 7 (1968) 1855-1863. (58) M. L. Wolfrom and A. Thompson, Methods Carbohydr. Chem., 3 (1963) 143-150. (59) J. Conchie, A. J. Hay, and J . A. Lomax, Carbohydr. Res., 103 (1982) 129-132.

CLEAVAGES OF POLYSACCHARIDE GLYCOSIDIC LINKAGES

27 I

more information on determination of structure by use of enzymes, an excellent article is available.60

VII. REDUCTIVECLEAVAGE One drawback of methylation analysis of polysaccharides is that the carbon atom involved in the cyclic acetal of a particular monosaccharide is not distinguished from linked positions after hydrolysis of the permethylated polysaccharide. For example, a 4-linked aldohexopyranose gives the same methylation product after acid hydrolysis as a 5-linked aldohexofuranose. By the application of a method that cleaves the glycosidic linkage with the addition of hydride, instead of water, reduction of the anomeric carbon atom is achieved while still maintaining the ring ~ t r u c t u r e . ~If' - this ~ ~ method is applied after permethylation, the linkage position is unequivocally identified. Added advantages of this method are that the anhydroalditol that is generated is stable and, for aldoses, a mixture of anomers is not formed, as there is no chirality at the formerly anomeric carbon atom; however, this means that the configuration of the linkages cannot be determined. The reductive-cleavage step is accomplished with boron trifluoride or trimethylsilyl trifluoromethanesulfonateassisted organosilane reduction. This method has already been applied to structural determination of several complex p o l y ~ a c c h a r i d e s ~and ~-~~ promises to become important. (60)B. V. McCleary and N . K. Matheson, Adv. Curbohydr. Chem. Biochem., 44 (1986) 147-276. (61) D. Rolf and G . R. Gray, J . A m . Chem. Soc., 104 (1982) 3539-3541. (62) D. Rolf and G . R. Gray, Curbohydr. R e s . , 152 (1986) 343-349. (63) J. A. Bennek, M. J . Rice, and G . R . Gray, Curbohydr. Res., 157 (1986) 125-137.

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ADVANCES IN CARBOHYDRATE CHEMISTRY AND BIOCHEMISTRY, VOL. 46

AQUEOUS, HIGH-TEMPERATURE TRANSFORMATION OF CARBOHYDRATES RELATIVE TO UTILIZATION OF BIOMASS

BY OLOFTHEANDER Swedish University of Agricultural Sciences, S-75007 Uppsala, Sweden

AND

DAVIDA. NELSON

PaciJc Northwest Laboratory, Richland, Washington 99352

I. Introduction. ........................................................... 11. Transformation of Monomeric Saccharides ........................... 1. Aldopentoses, Aldotetroses, and Aldotrioses ..... ............ 2. Hexoses and Alduronic Acids ......................................... 111. Transformation of Polysaccharides I . Starch . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

.......................

........................

3. Hemicelluloses and Glycuronans ....................................... IV. Carbohydrate Transformation in the Presence of Amino Compounds . . . . . . . . . V. Carbohydrate Transformation in Chemical Processes, Including Humus Formation. .............................................................

273 275 275 284 295 295 297 305 307 323

I. INTRODUCTION Over the past two decades, considerable interest has been directed toward the conversion of cellulosic biomass (such materials as wood wastes, bagasse, and straw) into useful products, notably fuels. Several procedures, including fermentation, gasification, liquefaction, and pyrolysis, have been commercially applied to carbohydrates with various degrees of success.' In order to use the polysaccharides present in lignocellulosic materials as a substrate in fermentation processes, pretreatments are necessary, such as with steam (under slightly acid conditions) or (1) P. M. Molton and T. F. Demmit, Polym. Plast. Technol. Eng., 11 (1978) 127-157.

273

Copyright 0 1988 by Academic Press, Inc. All rights of reproduction in any form reserved.

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OLOF THEANDER AND DAVID A. NELSON

alkali, followed by acid or enzymic hydrolysis. It is difficult to avoid some unwanted carbohydrate transformations in these pretreatments. Gasification is a rather direct and specific process. Liquefaction (hydrothermolysis) and pyrolysis2 are not so specific, as the mixtures obtained by these processes indicate that a complex series of mechanisms is involved. These two thermolytic processes appear related, because a significant number of their products are similar. The mechanism of pyrolysis has received more attention, because of the fundamental work of Shafizadeh3v4and B r ~ i d oHowever, .~ the routes to many of the similar products are not necessarily the same, because of the role of the aqueous solution in liquefaction. Thus, liquefaction may be regarded as a modification of the process of pyrolysis, but the lower temperatures and aqueous conditions present a chemistry rich in overlapping mechanisms and underlying confusion. A modification of the pyrolysis process, developed by Hoppe-Seylefi in 1871, involved the addition of water and alkali to biomass which was converted into oil, gas, water-soluble components, and carbonaceous material.'-" The addition of carbon monoxide and hydrogen in the liquefaction process allowed the production of liquid fuels from Asphalt substitutes have also been prepared from biomass under liquefaction conditions. I8 The research examined in this article will be confined to generally irre(2) P. Tomasik, M. Palasinski, and S. Wiejak, Adv. Carbohydr. Chem. Biochem., in preparation. (3) F. Shafizadeh, Adv. Carbohydr. Chem., 23 (1968) 419-474. (4) F. Shafizadeh and Y. L. Fu, Carbohydr. Res., 29 (1973) 113-122. (5) A. Broido, A. C. Javier-Son, A. C. Quano, and E. M. Barrall, J . Appl. Polym. Sci., 17 (1973) 3627-3635. (6) F. Hoppe-Seyler, Ber., 4 (1871) 15-16. (7) E. Berl and A. Schmidt, Justus Liebigs Ann. Chem., 461 (1928) 192-220. (8) E . Berl, A. Schmidt, and H. Koch, Angew. Chem., 43 (1930) 1018-1019. (9) E. Bed and A. Schmidt, Justus Liebigs Ann. Chem., 493 (1932) 97-123. (10) E. Bed and A. Schmidt, Justus Liebigs Ann. Chem., 496 (1932) 283-303. (11) F. Bergius, Min. J . (London) 163 (1928) 1067-1068. (12) A. H. Weiss, Text. Res. J . , 42 (1972) 526-533. (13) D. V. Gupta, W. L . Kranich, and A. H. Weiss, Znd. Eng. Chem. Process Des. Deu., 15 (1976) 256-260. (14) H. R. Appell, Y. L. Fu, S. Friedman, P. Yavorsky, and I. Wender, U . S . NTZS PB Rep., 1971, No. 203,669, 24 pp. (15) J. C. Cavalier and E. Chornet, Fuel, 56 (1977) 57-64. (16) H. I. Waterman and F. Kortlandt, Recl. Trav. Chim. Pays-Bas, 43 (1924) 691-701. (17) D. C. Elliott, in D. L. Klass and G. H. Emert (Eds.), Fuels from Biomass and Wastes, Ann Arbor Publishers, Ann Arbor, Michigan, 1981, pp. 435-449. (18) J. Donovan, R. Miller, T. Batter, and R. Lottman, EPA Rep. 6092-810242, 1981, NTZS PB 82-1 19082.

HIGH-TEMPERATURE TRANSFORMATION OF CARBOHYDRATES

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versible transformations occurring in aqueous systems at various pH values, at or above 100". The effect of oxidative conditions will usually not be discussed. Most of the processes of the pulping industry will be excluded, except those involving formation of products of low molecular weight. However, reports concerning the combination of carbohydrates with amino acids or amines will be discussed, as these nitrogen compounds may catalyze tautomerization, fragmentations, and certain rearrangements. Furthermore, amino acids or proteins are always present to some extent in all plant raw-materials.

11. TRANSFORMATION OF MONOMERIC SACCHARIDES 1. Aldopentoses, Aldotetroses, and Aldotrioses a. Acidic Conditions.-All aldopentoses form 2-furaldehyde in high yield when exposed to aqueous acid solution at elevated temperature. Such high yields are obtained only if the furaldehyde is removed, usually by distillation, as fast as it is formed.19 D-Xylose is the most effective of the pentoses,20as it can form a nearly quantitative yield of 2-furaldehyde. It is not completely clear why D-xylose has this enhanced ability compared to the other pentoses. However, the stereochemistry of the pentose and other competitive degradation routes apparently play significant roles in the yield of 2-furaldehyde. It has also been reported that 2,5-anhydro-~arabinose readily provides furaldehyde upon warming in an acidic solution.21 The mechanism of pentose dehydration has been a matter of study for several years. The accepted pathway (see Scheme 1) to 2-furaldehyde from a pentose, in this case D-xylose (l),involves the reversible formation of a l ,2-enediol(2) followed by dehydration to the enolic form (3)of a 3-deoxypentosulose, which is further dehydrated to the 3,4-dideoxypent3-enos-2-ulose (4) prior to cyclization22to afford 2-furaldehyde 5. This mechanism, initially suggested by I ~ b e 1 1has , ~ ~been substantiated by later This confirmation required incorporation of deuterium24or trit i u ~ n *into ~ the furaldehyde at various ring positions. However, when (19) C. D. Hurd and L. L. Isenhour, J . A m . Chem. SOC.,54 (1932) 317-330. (20) R. W. Scott, W. E. Moore, M. J. Effland, and M. A. Millett, AnalBiochem., 21 (1967) 68-80. (21) M. Cifonelli, J. A. Cifonelli, R. Montgomery, and F. Smith, J . Am. Chem. Soc., 77 (1955) 121-125. (22) M. S. Feather and J . F. Harris, Adu. Carbohydr. Chem. Biochem., 28 (1973) 161-237. (23) H. S. Isbell, J . Res. Natl. Bur. Stand., 32 (1944) 45-59. (24) M. S. Feather, Tetrahedon Lett., (1970) 4143-4145. (25) M. S . Feather, D. W. Harris, and S. B. Nichols, J . Org Chem., 37 (1972) 1606-1608.

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D-xylose was converted into 2-furaldehyde in acidified, tritiated water, no carbon-bound isotope was detected. This suggested that the 1,2-enediol (2) reacted immediately, as otherwise, tritium would have been detected at the aldehydic carbon atom of 2-furaldehyde, as a result of aldoseketose interconversion.26 An acidic dehydration performed with ~ - [ 2 3H]xylose showed that an intramolecular C-2-C- 1 hydrogen transfer had actually occurred.26 Thus, these data indicated that an intramolecular hydride shift is more probable than the previously accepted step involving a 1,2-enediol intermediate.

1

2

3

4

SCHEMEI .-Formation of 2-Furaldehyde from D-Xylose.

Although small proportions of other products are formed when D-XYlose is exposed to rather high acid concentrations, arabinose, lyxose, and ribose form considerably more of alternative products (generally reductic acid) than of 2-furaldehyde under these conditions.20Reductic acid (2,3dihydroxy-2-cyclopenten- 1-one, 47) has been detected as a product after acid exposure of ~ - x y l o s or e ~its ~ major dehydration product, 2-furaldehyde.2xFurther work performed with D-[ l-14C]xyloseand [a-I4C]2-furaldehyde showed that reductic acid having identical label distribution was obtained from both starting materials.29This indicated that a common primary source was involved, probably 2-furaldehyde, as it is readily formed from D-xylose under acidic conditions. D-Xylose and D-arabinose have been treated with a 0.5M acetate buffer (pH 4.5) at re flu^.^^ Besides 2-furaldehyde, some catechols and unique chromones were isolated from the reaction mixture in small proportions. These included 3,8-dihydroxy-2-methylchromone and its precursor, 5,6,7,8-tetrahydro-3,5-dihydroxy-2-methyl-8-oxochromone. A trihydroxy-2-methylchromone was also isolated from the D-xylose reac(26) (27) (28) (29) (30)

D. W. Harris and M. S. Feather, J . Org. Chem., 39 (1974) 724-725. T. Reichstein and R. Oppenauer, Helu. Chim. Acta, 16 (1934) 390-396. Dutch Pat. 61,296 (1948); Chem. Abstr., 42 (1948) 7788. M. S. Feather, J . Org. Chem., 34 (1969) 1998-1999. T. Popoff and 0. Theander, Carbohydr. Res., 27 (1972) 135-149.

HIGH-TEMPERATURE TRANSFORMATION OF CARBOHYDRATES

277

tion mixture. A preparative-scale technique using liquid chromatography has been developed for the isolation of 3,8-dihydroxy-2-methylchromone from the D-xylose reaction-mi~ture.~' Several low-molecular-weight aldehydes (formaldehyde, acetaldehyde, and 2-butenal) have also been isolated from D-xylose after acid treatment.32 Both ~-[l-'~C]xylose and ~-[5-'~C]arabinose were exposed to a concen1-Hydroxy-2-propanone (acetrated phosphate buffer solution (pH 6.7).33 tol) was distilled from the heated solution. Radioassay indicated that similar labeling [3-14C]occurred in the acetol from both pentoses, with loss of the configurational difference; thus, a 3-ketopentose or its enediol was suggested as an intermediate. Further work with 3-0- and 6-O-methyl-~glucose and with 1-0-methyl-D-fructose indicated that p-elimination from a 3-ketose or, in the case of a hexose, from a 3-ketose or a 4-ketose, or both, tautomerization of the resulting a-diketone to a P-diketone, and hydrolytic cleavage are essential steps34in the formation of acetol. A bicyclic y-pyranone was isolated in -1% yield from an acidified, refluxed solution of D-erythrose (6).35It was proposed that the compound, 4a,5,6,7a-tetrahydrocyclopenta[b]pyran-4,7-dione (lo), is formed (by way of 9) from two molecules of D-erythrose, namely, an enediol (8) and a dehydrated form (7). Feather and Harris22pointed out that D-erythrose would lose two molecules of water to form an intermediate (7) prior to coupling with the enediol 8 (see Scheme 2) to give 9. D-Erythrose has also been exposed to a boiling solution in pH 4.5 buffer.36Low yields (95% under suitable acidic condition^."^ Acid hydrolysis is quite dependent upon pH, and the rate of hydrolysis is appreciable, even below loo", if the acid concentration is high. For instance, cellulose forms a homogeneous solution in 51% sulfuric acid at 18", and the rate constant for hydrolysis under these conditionsIZ0is 5.1 X M. R. Stetten and H. M. Katzen, J . A m . Chem. SOC., 83 (1961) 2912-2918. R. L. Whistler and J. N . BeMiller, Arch. Biochem. Biophys., 98 (1962) 120-123. D. J. Manners, Adu. Carbohydr. Chem., 17 (1962) 371-430. 0. Theander, in R. P. Overend, T. A. Milne, and L. K. Mudge (Eds.), Fundamenfals of Thermochemical Biomass Conversion, Elsevier Applied Science Publishers, New York, 1985, pp. 35-60. (119) B. Philipp, Pure Appl. Chem., 56 (1984) 391-402. (120) S. A. Rydholm, Pulping Processes, Interscience, New York, 1965, pp. 124-127.

(115) (116) (117) (118)

OLOF THEANDER AND DAVID A. NELSON

298

lo-' s-1. Several rate-studies were performed in 8 0 4 6 % phosphoric acid, as it provided a lower rate of hydrolysis than that of sulfuric acid.I2' Similar work was also performed in concentrated hydrochloric acid.'22 The kinetics of cellulose hydrolysis in dilute acid (0.4-1.6% H2S04) at 170- 190" has been in~estigated.'~~ Further acid-hydrolysis studies were performed at 75-80" with 0.5 M H2S04 with cellulose and c e l l ~ b i o s e . ~ ~ ~ The results of this work suggested that hydrolysis is initially confined to the amorphous regions of cellulose. After their depletion, degradation begins upon the ends of the crystallites. Other systems used for cellulose hydrolysis include trifluoroacetic acid,'25and mixtures of acetic acid, acetic anhydride, N,N-dimethylformamide, and sulfuric acid.'26 Cellobiose was used as a model for cellulose under acid-hydrolysis condition^.'^^ This investigation used 0.01 A4 H2SO4 and 1.O% cellobiose to evaluate the first-order kinetics of the hydrolysis of cellobiose to D-glucose. The results of an Arrhenius diagram indicated that the activation energy for this hydrolysis was 133 kJ.mo1-I. Temperatures from 160 to 220" were examined during the hydrolysis of cellobiose.

R- 0 Q - R -

R-0

OH

64

QC1. OH

R-0

4,

t

L+H20 R - Q

OH

OH

65 66 67 SCHEME 11 .-Mechanisms for the Acid-catalyzed Hydrolysis of Cellulose.

The mechanism of the acid-catalyzed hydrolysis of cellulose is based on that normally expected for an acetal12*(see Scheme 1 1 ) . This involves formation of a conjugate acid by protonation of either of the acetal oxygen atoms at C-1, and formation of a carbonium ion, followed by stabilization of the product by heterolysis of a participating water molecule. The carE. C. Sherrard and A . W. Froehlke, J . Am. Chem. Soc., 45 (1923) 1729-1734. F. Bergius, Br. Pat. 315,198 (1928); Chem. Absrr., 24 (1929) 1739. J. F. Saeman, Ind. Eng. Chem., 37 (1945) 43-52. A. Sharples, Trans. Faraday SOC., 53 (1957) 1003-1013. D. Fengel and G . Wegener, in R. D. Brown, Jr., and L. Jurasek (Eds.), Hydrolysis of Cellulose: Mechanisms of Enzymatic and Acid Catalysis, Adu. Chem. Ser., 181 (1979) 145-158.

K. Garves, in Ref. 125, pp. 159-165. 0 . Bobleter, W . Schwald, R. Concin, and H. Binder, J. Carbohydr. Chem., 5 (1986) 387-399.

L. P. Clermont and A. Schwartz, Pulp Pap. Mag. Can., 53 (1952) 142-143.

H'

HIGH-TEMPERATURE TRANSFORMATION OF CARBOHYDRATES

299

bonium ion may be either cyclic or acyclic, depending upon the primary site of p r o t o n a t i ~ n .It' ~was ~ suggested that a hydronium ion may partially protonate both oxygen atoms of the acetal by forming a six-membered ring. The rate of the acidic cleavage of cellulose, compared to that of smaller glycosides, is lower by one or two orders of magnitude, because of the tertiary structure of cellulose and the limited accessibility of the acetal groups. Aldobiouronic acid linkages in polysaccharides are known to be more stable towards acid hydrolysis than ordinary glycosidic linkages; strong evidence suggested that polar and conformational effects are operative. I3O The rates of hydrolysis of cellobiose, pseudocellobiouronic acid (carboxyl group in the reducing unit), and cellobiouronic acid were studied as models for the oxidation of the primary hydroxyl groups of cellulose to carboxyl groups. The rates of hydrolysis of the two former compounds were almost identical; whereas, the rate of hydrolysis of cellobiouronic acid is considerably lower. I 3 I Introduction of carbonyl groups into cellulose, and other polysaccharides, by bleaching has a large effect on hydrolysis.I3*Keto groups at C-2 or C-3 in cellulose increases alkali depolymerization by @-elimination at elevated temperatures. The oxidation of primary hydroxyl groups to aldehydo groups increases the depolymerization of cellulose for similar Experiments conducted at 80" indicated that @-eliminationwas also responsible for the depolymerization of cellulosic material under neutral or slightly acid conditions; this occurred down to at least pH 3.5. However, at pH 1.2 and 80", acid-catalyzed hydrolysis of the glycosidic bonds of oxidized cellulose occurred, because of the presence of the 6-aldehydo group.133 Cellulose is readily hydrolyzed in water at >170" at a rate that depends on the hydrogen-ion concentration, in the range between pH 5 and 8. Because acids from the degradation of D-glucose are produced when cellulose is exposed to high temperature, the pH of the aqueous mixture drops in the absence of buffers. Earlier work'35J36had indicated that ether-soluble products could be obtained by heating cellulose in (129) B. Philipp, V . Jacopian, F. Loth, W. Hirte, and G . Schulz, in Ref. 125, pp. 127-143. (130) 0.Theander, in W. Pigman, D. Horton, and J . D. Wander (Eds.), The Carbohydrates, Vol. IB, Academic Press, New York, 1980, pp. 1013-1099. (131) I. Johansson, B. Lindberg, and 0. Theander, Acta Chem. Scand., 20 (1963) 20192024. (132). 0. Theander, Tappi, 48 (1965) 105-110. (133) A. E. Luetzow and 0. Theander, S u m . Papperstidn., 77 (1974) 312-318. (134) B. B. Mithel, G . H . Webster, and W. H. Rapson, Tappi, 40 (1957) 1-4. (135) P. A. Bobrov, J . Appl. Chem. USSR, 6 (1933) 1105-1110. (136) H. Tropsch, Brennst. Chem., 5 (1924) 288-289.

300

OLOF THEANDER AND DAVID A. NELSON

water at 275". In the absence of any added acid or base, the major products of the hydrothermolysis of cellulose after 2.5 min at 300" were 30% of 11, 13% of 2-furaldehyde (3,and >30% of saccharides [including Dglucose, cellobiose, D-mannose, D-fructose, and 1,6-anhydro-fi-~-glucopyranose (levoglucosan)] .37 These results with cellulose are somewhat similar to those obtained by using'37 a flow system (rapid removal of products) for 5 min at 264". The major products were 42.6% of D-glucose, 12.1% of 11, 4.8% of cellobiose, 5.2% of D-fructose, and 1.0% of Dxylose. The presence of 1,6-anhydro-fi-~-glucopyranose~~ could indicate the lack of homogeneity within the hydrothermolytic reactor, and a concurrent pyrolytic process. The pyrolytic degradation of cellulose involves the initial formation of levoglucosan without first converting the cellulose into D-glucose.'38A lack of homogeneity may also have been the source of 40% of levoglucosan when cellulose was treated with superheated steam at diminished pressures.'39 It should be noted that levoglucosan is also f ~ r m e d ' ~after ~ J ~ the ' alkaline hydrolysis of cellobiitol at 170". Furthermore, levoglucosan is also present after the alkaline hydrolysis of phenyl fi-~-glucosides.'~~ Rapid degradation of cellulose in the range of 250 to 350" also produces 5-methyl-2-furaldehyde, levulinic acid, biacetyl, and a methylfuranone. 143 Acid hydrolysis of cellulosic materials that include some hemicellulose, produces D-xylose, D-glucose, and cellobiose, as well as 11, 2-furaldehyde (3,levulinic acid, formic acid, and acetic acid.'@ In order to lessen the contamination due to hemicellulose, acid hydrolysis is generally performed in two steps: dilute sulfuric acid (1%) at 80-120" followed'45by 520% sulfuric acid at 180". The initial stage removes most of the pentoglycans (pentosans). The effect of alkaline solutions upon carbohydrates has been known for a considerable time, but the complexity of the reaction mixtures was not initially recognized as resulting from a combination of alkaline degrada(137) 0. Bobleter, R. Niesner, and M. Rohr, J . Appl. Polym. Sci., 20 (1976) 2083-2093. (138) D. Gardiner, J . Chem. Soc., (1966) 1473-1476. (139) Ya. A. Epshtein, 0. P. Golova, and L. I. Durynina, Izu. Akad. Nauk SSSR, Otd. Fiz. Mar. Khim. Nauk, (1959) 1126-1127. (140) E. Dryselius, B. Lindberg, and 0. Theander, Acta Chem. Scand., 11 (1957) 663-667. (141) R. E. Brandon, L. R. Schroeder, and D. C. Johnson, in A. F. Turbak (Ed.), Cellulose Technology Research, ACS Symp. Ser., 10 (1975) 125-146. (142) C. M. McCloskey and G . H . Coleman, J . Org. Chem., 10 (1945) 184-192. (143) R. Krishna, M. R. Kallury, C. Ambridge, T. T. Tidwell, D. G. B. Boocock, F. A. Agblevor, and D. J. Stewart, Carbohydr. Res., 158 (1986) 253-261. (144) H. E. Grethlein, Biorechnol. Bioeng. Symp., 5 (1975) 303-318. (145) A. E. Humphrey, in Ref. 125, pp. 15-53.

HIGH-TEMPERATURE TRANSFORMATION OF CARBOHYDRATES

301

tion and oxidation r e a c t i ~ n s . Once ~ ~ ~the J ~ importance ~ of the exclusion of oxygen was realized, great strides were made toward understanding the chemistry of the alkaline degradation of cellulose.14s The initial interaction between cellulose and metal hydroxides appears to be salt formation occurring at the reducing, terminal, D-glucose unit (enediol form).149Because a tautomeric shift is needed in order to form the enediol from an aldehyde, salt formation is usually relegated to the reducing terminal units of cellulose. The initial suggestion*50concerning alkali attack only at the reducing end of cellulose has received considerable experimental s ~ p p o r tHowever, . ~ ~ ~ ~ above ~ ~ 170", ~ dilute sodium hydroxide attacks cellulose at random midpoints, as well as at the reducingterminal end.153J54Thus, all the newly formed terminal groups are available for cleavage (peeling). The random cleavage, or alkaline scission,lS5may occur by intramolecular d i ~ p l a c e m e n tor ' ~by ~ the addition of the hydroxyl ion.157 Below 170", the stepwise-peeling mechanism follows the theory of /3alkoxycarbonyl e l i m i n a t i ~ nScheme .~~ 12 represents the sequential process involving the elimination of D-glucoisosaccharinic acid (52) as the terminal unit of alkali-exposed cellulose. IS1 Most of the mechanistic work was performed with hydrocellulose (cellulose pretreated with hot, dilute hydrochloric acid), in order to provide a uniform and highly crystalline starting-material. The intermediate 70 has been isolated from model systems, including 4-O-methyl-~-ghcose and maltose, as well as the polysaccharides cellulose and a m y l o ~ e Alkaline . ~ ~ ~ reactions performed at 100" with calcium hydroxide double the formation of 52 from cellulose, compared to those performed with NaOH. A study of cellobiose exposed to dilute NaOH at 90" provided an isolated ketodisaccharide having a (146) (147) (148) (149)

(150) (151) (152) (153) (154) (155)

(156) (157)

J. U. Nef, Justus Liebigs Ann. Chem., 403 (1914) 204-383. W. L. Evans, Chem. Rev.. 31 (1942) 537-560. R. L. Whistler and J. N. BeMiller, Adv. Carbohydr. Chem., 13 (1958) 289-329. J . A. Rendleman, Jr., Ionization of Carbohydrates in the Presence of Metal Hydroxides and Oxides, Adv. Chem. Ser., 117 (1973) 51-69. G . F. Davidson, J . Text. Inst., 25 (1934) ~ 1 7 4 - ~ 1 9 6 . G. N. Richards and H. H. Sephton, J . Chem. Soc., (1957) 4492-4499. G. Machell and G . N . Richards, J . Chem. Soc., (1957) 4500-4506. W. M. Corbett and G. N. Richards, Sven. Papperstidn., 60 (1957) 791-794. 0. Samuelson, G. Grangord, K. Jonsson, and K. Schramm, Sven. Papperstidn., 56 (1953) 779-784. G. N . Richards, in N . M. Bikales and L. Segal (Eds.), High Polymers, Vol. 5 , WileyInterscience, New York, 1971, pp. 1007-1014. J . Janson and B. Lindberg, Acta Chem. Scand., 13 (1959) 138-143. R. J. Femer, W. G. Overend, and A. E. Ryan, J . Chem. Soc., (1965) 3484-3486.

302

OLOF THEANDER AND DAVID A. NELSON CHZOH

CHO

I

HCOH

I HOCH I HC-O+Glc)n

I I CH,OH

HCOH

CHzOH

I 1 HOCH I HC-O+Glc), c=o

I

HCOH

I

c= 0

I

I

HCOH

I

+

H ;:I I CHzOH

CHzOH 'O

68

CHO

I c= 0 I

HOCH

I HC-O+Glc),I HCOH I CHzOH

n

\

69

CHz

I I CHZOH

HCOH

52

SCHEME 12.-The Stepwise-peeling Mechanism Involving Cellulose.

(1 4)-glycosidic bond.15gThis lends support to the formation of 69, shown in Scheme 12. At higher temperatures, the products become more complex, and an increasing proportion of acids, such as formic, lactic, and acetic, is formed.'51 The formation of 7-8% of formic acid from cellulose is probably due to degradationg8of the reaction intermediates of 70. This degradation is accompanied by formation of glycolic acid (hydroxyacetic acid) and 3,4-dihydroxybutanoic acid. A marked difference in the product pattern has been reported for the treatment of cellobiose with either NaOH or NaHC03.159 The formation of 3-deoxy-2-O-(hydroxymethyl)pentonicacids (52) from cellobiose is less important in sodium hydrogencarbonate solution than in sodium hydroxide, while the relative amounts of 2-deoxytetronic, 3-deoxypentonic, and 3 ,Cdideoxypentonic acids are much larger. According to Scheme 12, the alkaline peeling of cellulose should continue until the entire polymer is degraded. However, cellulose dissolves partially, but not completely, in hot alkali, and this remaining polysaccharide contains an increased carboxyl content.I6O Thus, a second reaction is occurring that competes with the step-wise, peeling procedure. (158) H. Sihtola and L. Laamanen, C e / / u / .Chem. Techno/., 3 (1969) 3-8. (159) L. Lowendahl and 0. Samuelson, Acta Chem. Scund., Ser. B , 30 (1976) 691-694. (160) 0 . Samuelson and A. Wennerblom, Suen. Pupperstidn., 57 (1954) 827-830.

HIGH-TEMPERATURE TRANSFORMATION OF CARBOHYDRATES

303

This stopping or stabilization reaction with cellulose was presumed to involve a saccharinic acid rearrangement of the reducing group on the terminal D-glucose residue.I6l This mechanism was confirmed by the formation of D-glucometasaccharinic acid, which still remained attachedIs2 as the terminal unit (73).The stopping reaction is presented in Scheme 13. CHO

I HCOH I HOCH I HC-O+Glc), I HCOH

CHO

COZH

L O

CHOH

I I + HC--O+Glc)n I HCOH I CH2

CHZOH

68

72

I I

CHZ

I

HC-WGlc),

I

HCOH

I

CH,OH 73

SCHEME 13.-The Stopping Reaction Involving Cellulose.

The terminal D-glucometasaccharinic acid residue blocks further peeling; however, the rate of peeling is much greater than that of the stopping reaction. Thus, several hundred D-glucosyl residues are removed by peeling prior to stabilization by the terminal metasaccharinic acid residue.IS5 An increase in temperature favors increase in the rate of the stopping reaction over peeling, as the activation energies are 100 kJ.mol-' for peeling, and 134 kJ.mol-' for the stopping reaction.'62 Although D-glucometasaccharinic acid is the most abundant terminal unit of cellulose after high temperature (170") alkaline exposure, a large proportion (23%) of 2-C-methylglyceric acid terminal units has also been identified.'@ The methylglyceric terminal unit may be formed by the Lobry de Bruyn-Alberda van Ekenstein rearrangement of D-glucose, to provide a 3-keto group, followed by a retro-aldol reaction which allowed loss of hydroxyacetaldehyde. The remaining terminal unit can then eliminate a P-hydroxyl group at C-1, to afford an unstable 2,3-diketose which should undergo benzilic rearrangement to 2-C-methylglyceric acid. A minor proportion (1%) of 2-C-methylribonic acid was also observed as a component of the terminal units. It had previously been tentatively identified.150 (161) H. Richtzenhein and B. Abrahamsson, Suen. Pappersridn., 57 (1954) 538-541. (162) D. W. Haas, B. F. Hrutfiord, and K. V. Sarkanen, J . Appl. Polym. Sci., 1 I (1967) 587600. (163) M. H. Johansson and 0. Samuelson, Carbohydr. Res., 34 (1974) 33-43.

304

OLOF THEANDER AND DAVID A. NELSON

It had been suggested that many of the products identified as derived from the alkaline degradation of cellulose may be in question, due to varying proportions of lignin present.'@ However, much work over the ensuing 30 years has shown that this potential problem is moot. In fact, many of the aromatic products usually assumed to be due to the lignin are, in fact, products of cellulose d e g r a d a t i ~ n For . ~ ~ instance, cresols and various other alkylphenols have been identified'65J66by mass spectrometry as products of alkaline hydrothermolysis at 300".A considerable number of other low-molecular-weight products were also identified in the acetone-soluble fraction of hydrothermolyzed cellulose. These included furans, cyclopentenones, ketones, and alcohols. Mechanisms for the forand phenol from cellulose mation of 2,5-dimethyl-2-cyclopenten-l-one were proposed, based on small fragment~.'~' Although gas-liquid chromatography-mass spectrometry (g.1.c.-m.s.) is an excellent tool for the identification of minute amounts of products in such complex mixtures as those observed after the hydrothermolysis of cellulose, it must be combined with isolation, or other techniques. For instance, 2-methoxyphenol (guaiacol) had been tentatively identified by g . l . ~ . - m . s .;' ~however, ~ derivatization experiments could not confirm its presence.la This also emphasized the difficulty of working with mixtures containing more than 250 components, all in small amounts. To avoid this problem, caused by long reaction times, much shorter heating and quench periods were used for hydrothermoly~is.~~ This lessened the number of products considerably. After 5 min in 0.1 M Na2C03 at 300°,the major products from cellulose (33). Howwere catechol and 2-hydroxy-3-methyl-2-cyclopenten-l-one ever, neither was present in proportions of > l .5%. Other isolated produ c t from ~ ~ ~the alkaline hydrothermolysis of cellulose included acetic acid, acetol, biacetyl, acetoin, 2,3-pentanedione, 2,5-hexanedione, phenol, 4-methylphenol, 16, 19, and 3-methyl-2-cyclopenten-1-one. Of considerable interest was the detection of 2,5-dimethylbenzoquinone (61), 2,5-dimethyl-1,Cbenzenediol(63), acetoin (62), and butanedione (60)in mixtures form hydrothermolyzed cellulose.~OsThe results from experiments performed at 300" with [ l-*3C]acetoinsuggested that two molecules of biacetyl combined to form 61 and 63, as equal distribution was observed in four positions. This implied that a symmetrical pre(164) W. Funasaka and C. Yokokawa, Nippon Kagaku Zasshi, Ind. Chem. Sect., 56 (1953) 34-36. (165) P. M. Molton, R. K. Miller, J. A. Russell, and J. M. Donovan, in D. L. Klass (Ed.), Biomass as a Nonfossil Fuel Source, ACS Symp. Ser., 144 (1981) 137-162. (166) P. M. Molton, R. K. Miller, J. M. Donovan, and T. F. Demmitt, Carbohydr. Res., 75 (1979) 199-206. (167) R . K. Miller, P. M. Molton, and J. A. Russell, in Ref. 17, pp. 451-459. (168) D. A. Nelson, J. A . Russell, and P. M. Molton, in Ref. 118, pp. 1039-1050.

HIGH-TEMPERATURE TRANSFORMATION OF CARBOHYDRATES

305

cursor, such as biacetyl, was needed prior to an aldol reaction-cyclization. A reduction-oxidation mechanism is apparently involved which provides 63 and 62 after the bimolecular combination of biacetyl to form 61 (see Scheme 10).Confirmation of the intermediacy of 61 was achieved by combining 61 with acetoin under aqueous alkaline conditions; a yield well in excess of the theoretical, based upon acetoin alone, was obtained.

3. Hemicelluloses and Glycuronans The polysaccharides of hemicelluloses are related to those of cellulose, as they possess @-(1 + 4) linkages between the monosaccharide units. The hemicellulose polysaccharides are quite heterogeneous, because they can contain hexoses, pentoses, and, occasionally, alduronic acids. In general, they are composed of only 100-200 sugar units."* Galactoglucomannans are the major constituents (20%) of softwood hemicellulose. This polysaccharide contains D-glucopyranosyl and D-mannopyranosyl residues coupled by p-(1 j . 4) bonding, as well as some solitary (Y-Dgalactopyranosyl groups bonded to 0-6. Moreover, there are present 510% of arabinoglucuronoxylans (xylans or pentosans) that contain @-( 1 j . 4)-linked D-xylopyranose, side-chain substituted arabinofuranose, and 40-methyl-a-D-glucuronic acid. Hardwood hemicellulose contains glucuronoxylan (15-30%) as the main component, with a @-(I + 4)-linked Dxylose polymer backbone similar to that of softwoods. The bonding between 4-O-methyl-a-~-glucuronicacid and D-xylose is through 0-2 of the D-xylose, but only with - 10% of the available pentoses. Some 70% of the 0 - 2 or 0-3 atoms of D-xylose are acetylated. The structural considerations regarding hemicellulose have been reviewed. 169 Xyloisosaccharinic acid [2,4-dihydroxy-2-(hydroxymethyl)butanoic acid] is one of the major, alkaline-degradation products of wood xylan, in particular, that of birch. I7O The disaccharide, 2-O-~-xylopyranosyl-~arabinose, which was isolated as a hydrolysis product of corn-cob hemicellulose, is readily degraded at 100" in 15 mM Ca(OH), to acidic products, primarily saccharinic acids. Xylan oligosaccharides from corn-cob hemicellulose produced 2,4-dihydroxy-2-(hydroxymethyl)butanoic acid172when exposed to 0.02 M Ca(OH), at 25". However, it was noted that the xylan, itself, was stable at 100" in M NaOH. The major acidic component of the hemicellulose fraction of slash pine (Pinus elliotti) after acid hydrolysis was identified as 4-O-methyl-~-glucuronic (169) R. (170) E. (171) R. (172) R.

E. Timell, Adu. Carbohydr. Chem., 20 (1965) 409-483. S. Sjostrom, Tappi, 60 (1977) 151-154. L. Whistler and W. M. Corbett, J. Am. Chem. Soc., 77 (1955) 3822-3823. L. Whistler and W. M. Corbett, J. Am. Chem. Soc., 78 (1956) 1003-1005.

306

OLOF THEANDER AND DAVID A. NELSON

acid. 173 Exposure of this acid to calcium hydroxide solution produces a dibasic acid analogous to the monobasic D-glucoisosacchannic acid. The kinetics of the alkaline degradation ( M NaOH at 130-190”) of eight model compounds related to (4-~-methyl-D-g~ucurono)-D-xy~an has been r e ~ 0 r t e d . The I ~ ~ model compounds had no reducing groups, and the ratedetermining step in the alkaline degradation was the hydrolysis of the glycosidic bonds. The rate constants for the glucuronoxylans were greater by one order of magnitude than those for the corresponding pentose models. Several other models, including ~-arabino-(4,0-methyI-~-glucurono)-D-xylan, were examined under alkaline conditions. 175 Initially, Larabinose and 4-0-methyl-~-glucuronicacid were eliminated. The first step in the elimination of 4-0-methyl-~-glucuronicacid was the loss of the 4-methoxyl group and the formation of a 4,5-double bond. The reducingend residues were transformed into 3-deoxyaldonic end units by the stopping reaction. There are many other polysaccharides in lignocellulosic and “biomass” materials that are of technical interest, but they lie outside the scope of this chapter. One important type of polysaccharide is pectin, found in agricultural side-products. For instance, sugar beet, citrus, and potato pulp contain pectins. This complex group of polysaccharides has D-galacturonic acid as the principal back-bone constituent. L-Rhamnosyl groups seem to be included at intervals in the D-galacturonic acid backbone, and such other neutral sugars as L-arabinose, D-xylose, D-galactose, and Lfucose may also be present as side chains. Neutral galactans, arabinans, and arabinogalactans are often associated with these acidic polymers. Some of the carboxyl groups in the galacturonan chain are present as methyl esters. That substitution makes pectin solutions thermally sensitive to depolymerization by 0-elimination. Pectins, also like pentosans, can be transformed into 2-furaldehyde, in good yield, by aqueous acid at elevated temperatures. As discussed in Section II,2,a, alduronic acids and glycuronans are decarboxylated in hot aqueous acid. Stoichiometric proportions of carbon dioxide were produced when D-galacturonic acid, 2-0(4-0-methyl-a-~-glucopyranosyluronic acid)-D-xylose, and purified D-galacturonan (pectic acid) were boiled in concentrated hydriodic acid. 176 Many marine algae are rich in glycuronans. One of the more technically important materials is alginic acid, composed of D-mannuronic and L(173) R. L. Whistler and G . N. Richards, J . A m . Chem. Soc., 80 (1958) 4888-4891. (174) I. Simkovic, A. Ebringerovti, J. Hirsch, and J. Konigstein, Carbohydr. Res., 152 (1986) 131-136. (175) I. Sirnkovic, J. Alfoldi, and M. Matolova, Carbohydr. Res., 152 (1986) 137-141. (176) 0. Theander and P. Aman, Swed. J . Agric. Res., 9 (1979) 97-106.

HIGH-TEMPERATURE TRANSFORMATION OF CARBOHYDRATES

307

guluronic acids. The chromone 50 has been isolated'77 from alginic acid that had been autoclaved at 160".

IV. CARBOHYDRATE TRANSFORMATION I N THE PRESENCE OF AMINOCOMPOUNDS The reaction between sugars and amino compounds, usually termed the Maillard reaction, has been extensively studied,178and has been the subject of three recent symposia.178a*Initial interest in this type of reaction was directed toward explanations of melanoidin formation and its role in food chemistry. Further work involved the degradation encountered during the handling of food, especially dehydrated products. Hence, the reaction is also known as nonenzymic browning or, simply, browning. Because of interest in biomass utilization and in those model reactions which appear applicable in explaining the formation of products, and in improving their yields, this Section will be generally limited to reports that involve the chemistry of the Maillard reaction at elevated temperatures. The factors affecting the Maillard reaction include temperature, time, moisture content, concentration, pH, and nature of the r e a c t a n t ~ . l It ~~~~l has been shown that, out of 21 amino acids, glycine, lysine, tryptophan, and tyrosine provide the most intense browning when exposed to five saccharides, especially a-lactose. 18* The Maillard reaction is also responsible for the decreased availability of lysine in proteinaceous foods. 1 8 3 ~ 1 8 4 The kinetics of the Amadori-compound formation from D-glucose and Llysine, as well as melanoidin formation, has been examined.'85 The socalled Amadori compounds are formed at an exponential rate, while showing pseudo-first-order disappearance of L-lysine in the presence of (177) K. Aso, Nippon Nogei Kagaku Kaishi, 10 (1934) 1189-1200. (178) G . P. Ellis, Adu. Carbohydr. Chem., 14 (1959) 63-134. (178a) C. Ervksson (Ed.), Maillard Reactions in Food, Prog. Food Nutr. Sci., Vol. 5 , Pergamon Press, Oxford, 1981. (178b) G. R. Waller and M. S. Feather (Eds.), The Maillard Reaction in Foods and Nutrition, ACS Symp. Ser. 215, Washington, DC, 1983. (178c) M. Fujimaki, M. Namiki, and H. Kato (Eds.), Amino-Carbonyl Reactions in Food and Biological Systems, Dev. in Food Sci. 13, Elsevier, Amsterdam, 1986. (179) L. M. Benzing-Purdie, J. A. Ripmeester, and C. I . Ratcliffe, J . Agric. Food Chem., 33 (1985) 31-33. (180) H . E. Nursten, Food Chem., 6 (1981) 263-277. (181) G . Vernin, Parfums Cosmet. Aromes, 32 (1980) 77-89. (182) S. H. Ashoor and J. B. Zent, J . Food Sci., 49 (1984) 1206-1207. (183) R. E. Feeney, G . Blankenhorn, and H. B. F. Dixon, Adu. Protein Chem., 29 (1975) 135-203. (184) J. Mauron, in Ref. 178a, pp. 5-35. (185) C. M. Lee, B. Sherr, and Y.-N. Koh, J . Agric. Food Chem., 32 (1984) 379-382.

OLOF THEANDER AND DAVID A. NELSON

308

an excess of D-glucose, Formation of the Amadori compounds will be explained. The initiating reaction between aldoses and amines, or amino acids, appears to involve'78 a reversible formation of an N-substituted aldosylamine (75); see Scheme 14. Without an acidic catalyst, hexoses form the aldosylamine condensation-product in 80-90% yield. An acidic catalyst raises the reaction rate; and yet, too much acid rapidly promotes the Amino acids act in an autocatformation of l-amino-l-deoxy-2-ketoses.'78 alytic manner, and the condensation proceeds even in the absence of additional acid. A considerable number of glycosylamines have been prepared by heating the saccharides and an amine in anhydrous ethanol in the presence of an acidic c a t a 1 y ~ t . N.m.r. l~~ spectroscopy has been used to show that primary amines condense with D-ribose to give D-ribopyranosylamines. 188 CHO

I

HCOH

1HOCH I HCOH I HCOH I

CHpOH

NHR

I I

HCOH

-

CH,OH

- HpO

-

+HpO

HOQNHR

I

HCOH

OH

I

~H,OH 35

74

75

SCHEME 14.-Forrnation of N-Substituted Aldosylarnine by the Carbonyl-Arnine Reaction. ,

The next step of the Maillard sequence involves the conversion of the N-substituted aldosylamine (74 75) into a 1-amino-1-deoxy-2-ketose (79) by the Amadori rearrangement (see Scheme 15).189J90 Amino acids react with ketoses to form 2-amino-2-deoxyaldoses by the Heyns rearrangement,191which is closely allied to the Amadori rearrangement. As already mentioned, these rearrangements are acid-catalyzed, and involve prototropic shifts. An alternative pathway, which invokes a carbonium (186) J. E. Hodge, J . Agric. Food Chem., 1 (1953) 928-943. (187) G . P. Ellis and J. Honeyrnan, Adv. Carbohydr. Chem., 10 (1955) 95-168. (188) C. Chavis, C. de Gourcy, F. Durnont, and J.-L. Irnbach, Carbohydr. Res., I13 (1983) 1-20.

(189) J . E. Hodge, Adu. Carbohydr. Chem., 10 (1955) 169-205. (190) T. M. Reynolds, Adu. Food Res., 14 (1965) 168-283. (191) H. H. Baer, Fortschr. Chem. Forsch., 3 (1958) 822-910.

HIGH-TEMPERATURE TRANSFORMATION O F CARBOHYDRATES NHR

I

+

t

HC - OH2

74

' Ht -

H'

I HCOH I HOCH I HCOH I HCOH I

CH2OH

76

309

CH=NHR

d 7

I HCOH I HOCH I HCOH I HCOH I

CHNHR

10,

- HC

+

I

HOCH

I

HCOH

v -

I

HCOH

I

CH20 H

CYOH

n

78

SCHEME 15.-Mechanism

CHrNHR

I c=o I HOCH I HCOH I HCOH I

CHpOH

79

of the Amadori Rearrangement.

ion on C-1 of 77, rather than the iminium ion, has also been proposed.'92 The Amadori rearrangement has been demonstrated with primary and secondary a m i n e ~ ,as ' ~well ~ as with amino acids.'94The aminodeoxyketoses (79) formed with primary amines can react with a second aldose molecule. This allows a further Amadori rearrangement, and formation6s of a diketosamine (81). The diketosamine undergoes enolization, followed by a p-elimination, to afford 3-deoxyhexos-2-ulose and l-amino-ldeoxyket~se'~'(see Scheme 16). Cleavage of di-(l-deoxy-D-fructos-1y1)glycine in deuterium oxide failed'" to show incorporated deuterium in (39). Thus, it the 3-methylene group of 3-deoxy-~-erythro-hexos-2-ulose was suggested that a 1,2-hydride shift occurs, in preference to enolization, for the formation of 39, but further examination of the deuterium experiments, monitored by n.m.r. spectroscopy, indicated incorrect spectral as'signments, and confirmed that enolization was most probable during this reaction.'97 Electron-spin resonance (e.s.r.) spectra with characteristic hyperfine structure have been recorded during the initial stages of the Maillard reaction between various sugar and amino c o r n p o ~ n d s . The ' ~ ~ products responsible for the spectra appear to be N,N'-disubstituted pyrazine radical cations. The pyrazine derivatives are assumed to be formed by the bimolecular condensation of two- and t h r e e - c a r b ~ nenaminol '~~~ compo(192) A. Gottschalk, in A. Gottschalk (Ed.), Glycoproteins, 2nd edn., Vol SB, Elsevier, Amsterdam, 1972, pp. 141-157. (193) J. E. Hodge and C. E. Rist, J . Am. Chem. Soc., 74 (1952) 1494-1497. (194) K. Heyns and H. Breuer, Chem. Ber., 91 (1958) 2750-2762. (195) E. F. L. J. Anet, A m . J. Chem., 13 (1960) 396-403. (196) G. Fodor and J.-P.Sachetto, Tetrahedron Lett., (1968) 401-403. (197) E. F. L. J. Anet, Tetrahedron Lett., (1968) 3525-3528. (198) M. Namiki and T. Hayashi, in Ref. 178a, 81-91; and Ref. 178b, 21-46. (198a) T. Hayashi and N. Namiki, in Ref. 178c, 29-38.

3 10

OLOF THEANDER AND DAVID A. NELSON

fHO c=o

I

c=o

I

R

I

I

HOCH

CHZ

I

HCOH HCC H ,'"

II CoH I HOCH I

CHZNHR

I

'i="

/

HOCH

HCOH

I

CH,OH

I I

HCOH

79

39

HCOH

I

R

I

CHzOH

I

CHZOH

% so

I I HCOH I CHZOH HCOH

t

I

CHz'

'CH2

I

I

c=o

c=o

I I HCOH I HCOH I CHZOH

I

HOCH

HOCH

I

,IoH I

H OH

CHZOH

81

SCHEME16.-Mechanism

for the Cleavage of Diketosarnines.

nents involving the amino reactant. Product concentrations during the preliminary stages of the Maillard reaction suggested a sequence in which a glycosylamine was initially formed, followed by partial cleavage to reducing fragmentation. It was shown that N,N'-dialkylpyrazones, or mixtures of glycolaldehyde with amino compounds were highly active in free radical formation as well as in browning. Production of C2 and C3 sugar fragments in a D-glucoselp-alanine system was negligible in acidic mixture but increased with pH in a manner parallel to the increase in browning.198a The results indicated that the proposed pathway plays an important role in the initial stages of browning in the Maillard reaction under neutral and alkaline conditions. (39) can be Scheme 16 shows that 3-deoxy-~-erythro-hexos-2-ulose formed by the cleavage of a diketosamine. Such an intermediate has already been implicated in the formation of S-(hydroxymethy1)-2-furaldehyde (see Scheme 7). Interest in 39 and its formation is directed towards its role in the production of two major groups of products observed in

HIGH-TEMPERATURE TRANSFORMATION O F CARBOHYDRATES

3I I

hydrothermolyzed biomass. These are the oxygen and nitrogen heterocyclic compounds. Flavor and aroma technologies have been concerned with volatile nitrogen and oxygen heterocycles produced by the Maillard reaction. Although several of these compounds may be present in hydrothermolyzed biomass, the extensive literatureIw will not be covered. Only that research which can be related to general mechanisms involving formation of the heterocycles will be discussed. During the course of the Amadori rearrangement, the 1 ,Zenolamine intermediate (82) can rearrange to form 3-deoxyhexos-2-ulose (39) under aqueous conditions while releasing the amine or, more importantly, the amino acid200(see Scheme 17). The amino acid can undergo decarboxylt

I I

HCOH

I I

CHO

hoH CH

COH

I

COH HOCH

CH=NRR'

t Hi-

*

-Ha

HCOH CH20H 82

SCHEME 17.-Formation ment.

I I HCOH I

HCOH

CH20H

i- H20

CHO

I c=o

I

I!

CH

-a

A 7

HLOH

I I

HCOH CH20H

I I HCOH 1 CH2

HCOH

I

CH20H

83 38 39 of 3-Deoxyhexo-2-dose by Way of the Amadon Rearrange-

ation to an aldehyde by the Strecker degradation. In fact, isovaleraldehyde, formed from L-leucine, has been used as an early indication of the Maillard reaction during thermal processes.2o0Not only does decarboxylation of the amino acid occur, but the amino group may be transferred to a carbonyl compound which is thereby reduced.201The carbonyl compound may contain an a-dicarbonyl grouping, such as 3-deoxy-~-erythro-hexos2-ulose (39). Cyclization of the resulting amino saccharide (for instance, derived from D-fructose and L-alanine in slightly acidic solution at reflux), or some of its dehydration products, yields various heterocyclic components,202such as the acylpyrroles, 5-methylpyrrole-2-carboxaldehyde(84) (199) S. Fors, in Ref. 178b, pp. 185-286. (200) K . Eichner and M. Ciner-Doruk, in Ref. 178a, pp. 115-135. (201) T . Nyhammar, K. Olsson, and P.-A. Pernemalm, in Ref. 178b, pp. 71-82. (202) P. E . Shaw and R. E. Berry, J. Agric. Food Chem., 25 (1977) 641-644.

OLOF THEANDER AND DAVID A. NELSON

312

f,="

84

85

87

86

39

88

SCHEME 18.-Mechanism for Acylpyrrole formation from 3-Deoxyhexos-2-dose by the Strecker Degradation.

and 2-acetylpyrrole (86) (see Scheme 18). Methylpyridinols, such as 6methyl-3-pyridinol (87), 2-methyl-3-pyridinol(88), and the acylpyrroles, 84 and 86, were obtained by refluxing D-glucose and glycine under acidic The results of labelling experiments with conditions (pH 2, 3, and 6).201,203 D-( l-13C)glucosewere consistent with the proposed mechanism for the formation of 84, shown in Scheme 18. However, little or no 86 was formed after 3-deoxy-~-erythro-hexos-2-ulose was subjected to the same acidic refluxing conditions. A mechanism that does not require 39, or its derivatives, as an intermediate has been proposed.203Elimination of the 2-hydroxyl group of D-glucose to afford the enamine (91) of 2-deoxy-~-urubino-hexose is assumed to occur by lactonization of the imine formed from glycine and D-glucose. A related, but less-direct route to 91 was also proposed. Although 2-deoxy-~-urubino-hexosewas not detected in the reaction mixtures, it was assumed that this was due to much faster pelimination involving dehydration of the enamine 91 compared to its hydrolysis. This process, leading to the formation203of 86 and 88, is presented in Scheme 19. As Scheme 19 indicates, the reaction between glycine (89) and D-glucose is quite dependent upon a number of sequential steps, any one of which can be misdirected to another product. This complexity was found (203) T. Nyhammar, K. Olsson, and P.-& Pernemalm, Acra Chem. Scand., Ser. B, 37 (1983) 879-889.

HIGH-TEMPERATURE TRANSFORMATION OF CARBOHYDRATES

3 I3

H3N CHzCO; CH=NCH2COF

89

I

t

CHO

I I

HCOH HOCH HlOH HCoH

I

- HCoH

HojH HCOH I I

HCOH

CHNH,

CH=NH

CH,NHz

CHzNH2

CH

CH

CH

CH

I I HOCH I - I HCOH

I

HCOH

I

I

I

CH HCOH

I

HCOH

I

CH2OH

CH zOH

CHzOH

90

91

92

I II

Amadori

CH

Steps

C=O

-

I

I

HCOH

I

CH20H

93

I II

- I

fl

86

CH c=o

I I

88

c=o CH3

94

CHzOH

35

SCHEME 19.-Mechanism for Formation of 2-Acetylpyrrole and 2-Methyl-3-pyridinol.

in the reaction between glycine and D-glucose in slightly acidic, aqueous solution. The products included D-fructose, furans, pyrroles, pyridines, phenols, carboxylic acids, and lactones.zMIt is notable that metasaccharinic acids (isolated as lactones), normally formed under alkaline conditions, were formed in acid in the presence of glycine. The pyrroles formed included not only 86 and 88, but also 2-formyl-5-(hydroxymethyl)1-methylpyrrole (98), 2-formyl-5-methylpyrrole-1-acetic acid, 2-formyl-5(hydroxymethy1)pyrrole-1-acetic acid (96), and 6-formyl-3,4-dihydro-3oxopyrrolo[1,2-a]pyrazine-2(1H)-acetic acid (97). Compounds 96 and a7 are of interest, as a bicyclic heterocycle had been formed from the original pyrrole by addition of a second molecule of glycine (see Scheme 20). The structures of 2-formyl-5-methylpyrrole- 1-acetic acid and 96 have been confirmed by synthesis.z052-Formyl-5-(hydroxymethyl)-l-methylpyrrole (98) had previously been observed as a product of the interaction of glycine and D-fructose.zMSeveral other bicyclic compounds were isolated from the reaction of D-glucose with glycineZMor methylamine,z07including furans, pyrroles, pyridines, and a pyrogallol derivative. The reaction between L-rhamnose and ethylamine producedz0*l-ethyl2-formyl-5-methylpyrrole and 2-acetyl-1-ethylpyrrole. Pyrroles such as 2formyl-5-(hydroxymethyl)-l-methylpyrrole (98) have also been detected (204) K. Olsson, P.-A. Pernemalm, and 0. Theander, Acta Chem. Scand., Ser. B , 32 (1978) 249-256. (205) K. Olsson and P.-A. Pernemalm, Acfa Chem. Scand., Ser. B , 32 (1979) 125-132. (206) H. Kato, H. Sonobe, and M. Fujimaki, Agric. Biol. Chem., 41 (1977) 711-712. (207) K. Olsson, P.-A. Pernemalm, T. Popoff, and 0. Theander, Acra Chem. Scand., Ser. B, 31 (1977) 469-474. (208) H. Kato, H. Shigematsu, T. Kurata, and M. Fujimaki, Agric. Biol. Chem., 36 (1972) 1639-1642.

3 I4

OLOF THEANDER AND DAVID A. NELSON

H'OH LOH

39

+ 89

+

How*cHo 96

SCHEME20.-Formation

97

of a Dihydropyrrolopyrazine.

as products of the reaction of D-glucose with methylamine in dilute acetic a ~ i d .The ~ ~anhydro ~ - ~ dimer ~ of 98, formed by dehydration of the 5hydroxymethyl group, was also observed.207An analogoue of 98 was obtained from the reaction of D-glucose and L-lysine.2'0*211 This product, 6-[2-formyl-5-(hydroxymethyl)pyrrol1-yllnorleucine (99), was formed in 2.1% yield at pH 4.5and 100". Only the 6-amino group was involved in the formation of this Maillard reaction-product. Several other compounds, such as 84 and 86-88 were present, but they represented utilization of the a-amino

98

99

100

(209) G. R. Jurch and J. H. Taturn, Curbohydr. Res., I5 (1970) 233-239. (210) R. K. Miller, K. Olsson, and P.-A. Pernernalrn, Acta Chem. Scund., Ser. B , 38 (1984) 689-694. (211) H. Kato, T. Nakayarna, S . Sugirnoto, and F. Hayase, Agric. BidChern., 46 (1982) 2599-2600.

HIGH-TEMPERATURE TRANSFORMATION OF CARBOHYDRATES

3 I5

Aqueous solutions of L-proline and D-glucose have been exposed to a temperature of 150" in order to prepare a series of unique products that included the pyrrolidine ring of p r ~ l i n e . ~ 'Of ~.~ considerable '~ interest was214the formation of 2,3,6,7-tetrahydro-7-methylcyclopent[b]azepin8(lH)-one (100). It was shown that cyclic a-dicarbonyl compounds (in equilibrium with enolones) appeared to act as precursors, in conjunction with L-proline, by way of a Strecker degradation to afford the azepines. It was suggested that the cyclic a-dicarbonyl compounds are formed during the Maillard reaction by an aldol reaction from glycolaldehyde, pyruvaldehyde, and other components, produced by retro-aldol cleavage of D-glucose. A series of cyclic enolones, such as 2-hydroxy-3,4-dimethyl-2-cyclopenten-1-one 34, were heated with L-proline or pyrrolidine, to gain evidence as to the mechanism. Several products, based on the 2-( 1-pyrrolidinyl)-2-~yclopenten1-one structure, were isolated. Furthermore, the concentration of the cyclopent[b]azepines was increased by three orders of magnitude when the cyclic enolones were substituted for saccharides and combined with L-proline. Studies were also conducted with hydroxy-L-proline and D-glucose or ~ - r h a m n o s e , *as~ ~ well as Larabinose and D-erythrose,215 in water at 100- 150". Hydroxy-L-proline combines with a-dicarbonyl compounds, forming iminium carboxylate intermediates that are decarboxylated and dehydrated to 1-pyrrolyl-2-oxo product^.^'^ For example, pyruvaldehyde, 2,3-butanedione and 1,2-cyclopentanedione, respectively yielded 1-acetonylpyrrole, 3-(l-pyrrolyl)-2butanone and 2-(1-pyrrolyl)cyclopentanone.No pyrazines were observed in the hydroxy-L-proline reaction-mi~tures.~'~ Alkylated pyrazines are generally formed when aqueous solutions of saccharides plus amino acids are heated at reflux. These products have and several been implicated as potent odorants in cooked roasted food D-Glucose or D-fructose in combination with Lasparagine or L-glutamic acid was examined2I7for total pyrazine content after dissolution in aqueous diethylene glycol at 120". Labelling experiments with D-[1-14C]glucoseand L-alanine or. L-asparagine indicated that (212) R. Tressl, K. Griinewald, and B. Helak, in P. Schreier (Ed.) Flavour 81, Weurman Symp., 3rd, Walter de Gruyter, Berlin, 1981, pp. 397-416. (213) R. Tressl, B. Helak, H. Koppler, and D. Rewicki, J . Agric. Food Chem., 33 (1985) 1132-1137. (214) R. Tressl, K. G. Griinewald, E . Kersten, and D. Rewicki, J. Agric. Food Chem., 33 (1985) 1137-1 142. (215) R. Tressl, K . G. Griinewald, E . Kersten, and D. Rewicki, J . Agric. Food Chem., 34 (1986) 347-350. (216) P. Marce and D. Hadziyev, Can. Znst. Food Sci. Technol. J . , 10 (1977) 272-279. (217) P. E. Koehler, M. E. Mason, and J. A. Newell, J. Agric. Food Chem., 17 (1969) 393396.

OLOF THEANDER AND DAVID A. NELSON

316

TABLEI Pyrazines Formedfn from the Reaction of D-Glucose(G1c) with Glycine(G1y) at 300" and pH 4.5 Yield (wt. % of total product) Glc: Gly(1 M :2 M ) 1omin

Pyrazine

Smin

MethylDimethyl- (2,5- and 2,6) 2,3-Dimethyl- and ethylTrirnethylTetrarnethylOther C,-alkyl-

0.30 0.80 0.34 2.18 0.61 0.10

0.33 0.85 0.39 2.21 0.57 0.09

Glc: Gly(1 M :1 M) Smin 10 min 0.25 0.38 0.11 0.30 0.05 0.03

0.30 0.48 0.13 0.41 0.06 0.04

the carbohydrate was the prime source of the carbon atoms in the product, and that the amino acid furnished only the nitrogen atom to the pyrazines. Fragmentation of the hexoses into C2-C4 units prior to pyrazine incorporation seems a most probable mechanism. The proportions of methyl- and dimethyl-pyrazine formed by D-glucose with various amino acids has been L-Asparagine produced the highest proportions of these two pyrazines, whereas glycine gave very little alkylpyrazine in the aqueous diethylene glycol system. The yields of alkylpyrazines increased with the addition of equimolar amounts of sodium hydroxide to the saccharide-amino acid solutions. Acetaldehyde and aqueous ammonia produced large proportions of unsubstituted pyrazine. However, when acetaldehyde reacted with L-asparagine, methyl- and dimethylpyrazines were also produced. The reaction of glycine and D-glucose at 300" was investigated in buffered acid.219The results concerning the formation of pyrazines are presented in Table I. The additional glycine, in the molar ratio of 2 : 1 with D-glucose, provided a higher proportion of pyrazines compared with stoichiometric reactions of the two components. This is particularly evident for the formation of trimethylpyrazine. Other components identified in these reaction mixtures were 5, 11,17, and 23.

(218) P. E. Koehler and G . V. Odell, J . Agric. Food Chem., 18 (1970) 895-901. (219) D. A. Nelson, R. T. Hallen, and 0. Theander, Absfr. Pap. Norfhwest Regional Meet. A m . Chem. SOC.,41st, Portland, Oregon, 1986, Abstr. 297.

HIGH-TEMPERATURE TRANSFORMATION OF CARBOHYDRATES

3 17

Several hexoses and pentoses were refluxed in 8 M aqueous ammonia.220The pentoses gave slightly larger yields of pyrazines than did the hexoses, but the types of pyrazines from both groups of saccharides were similar. Several possible pathways of formation for the pyrazines have been suggested, using various a-amino carbonyl intermediates.220*221 Scheme 21 shows the formation of 2-methylpyrazine (104) from two proposed fragments. The formation of the necessary carbonyl groups of the small fragmented compounds was assumed to be due to a retro-aldol reaction.220A mechanism has also been advanced for the formation of pyrazines by ammonia addition to cyclopentenone derivatives, and a subsequent condensation with a-amino carbonyl compounds.222

101

102

103

104

SCHEME21 .-Formation of 2-Methylpyrazine from Saccharide Fragments.

Studies have been conducted with the products obtained from refluxing A series of indoaqueous solutions of D-glucose with ~-phenylalanine.~~~ lines was identified; these included 3-phenylindoline (105), l-phenethylindoline (106), and 2-(indolin-l-yl)-3-phenylpropanoic acid (107). Several aldehydes formed by the Strecker degradation were also identified. The D-glucose-L-phenylalanine reaction was further in 1-octanol at 100-160". Several pyrroles were identified among the low-molecularweight products. The combination of DL-cysteine with D-galactose, in refluxing methanol containing a small proportion of pyridine and water, provided225the diastereomers (2S,4S and 2R,4R) of 2-(~-gulucto-hydroxypentityl)-4thiazolidinecarboxylic acid (108). The diastereomers can be separated by recrystallization, and then cleaved with acid, to yield resolved D- or Lcysteine. An investigation was conducted concerning the reaction be(220) T. Shibamoto and R. A. Bernhard, J . Agric. Food Chem., 25 (1977) 609-614. (221) T. Shibamoto and R. A. Bernhard, Agric. Biol. Chem.. 41 (1977) 143-153. (222) T. Shibamoto and R. A. Bernhard, J . Agric. Food Chem., 26 (1978) 183-187. (223) G . Westphal and E. CieSlik, Nuhrung, 26 (1982) 765-776. (224) G . Westphal and E. CieSlik, Nuhrung, 27 (1983) 55-62. (225) J. Martens and K. Drauz, Justus Liebigs Ann. Chem., (1983) 2073-2078.

OLOF THEANDER AND DAVID A. NELSON

318

105

tween L-cysteine and 4-hydroxy-2,5-dimethyl-3(2H)furanone(58) in water at 160".226Two thiophenes, 3-methyl-2-(2-oxopropyl)thiophene(109) and 2-methyl-3-propanoylthiophene(110), as well as 2,4-hexanedione, were the major volatile products. A mechanism was proposed for the formation of 109 and 110 via 2,4-hexanedione and 2-mercaptoacetaldehyde, both of which are present in the reaction mixture.

4 : Y HrioH

0

HO H

'I

H OH

I

QCkCCY CY

108

109

CWH

QCY

ccwcy

a

110

The formation of oxygen-containing heterocyclic compounds is also a consequence of the Maillard reaction. Amines and amino acids have a catalytic effect upon the formation of 2-furaldehyde (5),la65-(hydroxymethyl)-2-furaldehyde ( l l ) , I a 6 2-(2-hydroxyacetyl)furan (44),207and 4-hydroxy-5-methyl-3(2H)-furanone (111) (see Ref. 214). This catalytic effect can be observed with several other non-nitrogenous products, including m a l t 0 1 . ~The ~ ~ amino acid or amine catalysis has been attributed to the transient formation of enamines or immonium ions,Is3or the 1,2-2,3 enolization of carbohydrate^.^'^ Of interest is the detection of N-(Zfuroyl(226) C.-K. Shu, M. L. Hagedorn, and C.-T. Ho, J . Agric. Food Cbem., 34 (1986) 344-346. (227) J. E. Hodge, B. E. Fisher, and E. C. Nelson, Proc. Am. Soc. Brew. Cbem., (1963) 8492.

HIGH-TEMPERATURE TRANSFORMATION OF CARBOHYDRATES

3 I9

methyl)-L-alanine in acidic aqueous solutions of D-fructose and L-alanine after heating228at 90". It was assumed that formation of this compound followed a route somewhat similar to that of 2-(2-hydroxyacetyl)furan (44);that is, indicating an initial 2,3-enolization of D-fructose, followed by elimination of water (Scheme 8).59

111

The formation of 5-(hydroxymethyl)-2-furaldehyde(11)from Amadori compounds (79) such as 1-deoxy-1-p-toluidino-D-fructosein deuterium oxide has been described.229Although the product of this reaction is the same, namely, 11, as that obtained from the acidic dehydration of Dglucose, the pathway is not quite the same. Yields of 11from 79 are much higher than those from D-glucose, and the conditions for the reaction are considerably milder when using the Amadori compounds. There is apparently considerable equilibration between the 1-amino-1-deoxy-2-ketose (79) and its 1,Zen01 (82), and between 3-deoxyhexos-2-ulose (39) and its enol (38) during the dehydrations (see Scheme 7).230The weak acid, usually acetic acid, favors these equilibria more than does a strong acid. Thus, due to the presence of the amine substituent, 79 undergoes 1,2enolization to 82 much more readily than does a corresponding, unsubstituted sugar (D-glucose to 36, for instance). The intermediates (82,83, and 39) are more stable in weak acid, which increases the possibility of their equilibration with tautomers and the incorporation of solvent protons. Once 3-deoxyhexos-2-ulose (39) is formed, the sequence shown in Scheme 7 can contribute, until the final dehydration to 11.Similar results concerning the equilibrations were obtained with the Amadori products of pentoses and hexuronic acids, using tritiated water and deuterium oxide.231In these reactions, distribution of the respective isotopic label was determined for labeled 2-furaldehyde (5). The pentose-derived 5 contained 14% of deuterium at C-3, 5% at C-4, and none at C-5, whereas the hexuronic acid-derived 5 contained 50, 44, and 7% at C-3, C-4, and C-5, (228) K . Heyns, J. Heukeshoven, and K. H. Brose, Angew. Chem., Int. Ed. Engl., 7 (1968) 628-629. (229) M. S. Feather and K. R. Russell, J . Org. Chem., 34 (1969) 2650-2652. (230) M. S. Feather, in Ref. 178a, pp. 37-45. (231) K . B. Hicks and M. S. Feather, Carbohydr. Res., 54 (1977) 209-215.

320

OLOF THEANDER AND DAVID A. NELSON

respectively. Thus, considerable equilibration occurs prior to the formation of 5 , in contrast to that observed for unsubstituted pentoses and hexuronic acids. It had been suggested that 4-hydroxy-5-methyl-3(2H)-furanone(111) can be formed from a pentose and an amine by way of an Amadori compound and its 2,3-enoli~ation.~~~ Moreover, 111 has also been preacid pared from l-deoxy-l-(dibenzylamino)-~-arabino-2-hexulosuron~c (112), which was synthesized from dibenzylamine and D-glucuronic This indicates that two different Amadori compounds can undergo 2,3-enolization in weak acids) to afford 111. In strong acid, both Amadori compounds undergo 1,2-enolization to afford 2-furaldehyde. Three Amadori compounds were exposed to weak and strong acidic conditions; these were 112, l-(benzylamino)-l-deoxy-~-arabino-2-hexulosuronic acid, and 1-(benzy1amino)-1-deoxy-~-threo-2-pentulose.~~~ All three compounds produced 2-furaldehyde in strong acid, although the highest yield Howwas obtained from l-(benzylamino)-l-deoxy-~-threo-2-pentulose. ever, only 112 produced the furanone 111 under mildly acidic conditions. This confirms that, when the Amadori compounds are almost completely protonated, 1,2-enolization occurs, and 2-furaldehyde is formed. Under mildly acidic conditions, the (less-protonated) amino group allows 2,3enolization, and formation of 111,to predominate. Compound 112,a tertiary amine, is the least basic and, thus, the least protonated in mild acid. l-14C]-arabLabeling experiments with 1-deoxy-l-(dibenzylamino)-~-[ ino-2-hexulosuronic acid [ 1-14C] 112 indicated that the 14C label corresponded to the 5-methyl group of 111 (see Ref. 234). This is also consistent with a l-deoxy-2,3-dicarbonyl intermediate (115),and indicates that 111 is a decarboxylation product (see Scheme 22). The precise step entailing decarboxylation has not yet been determined. The carboxyl group could be carried through to ring closure (furanone formation). Such a step would provide a 2-carboxylate which is a p-keto acid subject to ready decarboxylation. The labeling information and the initial steps of the mechanism in Scheme 22 are also consistent with the formation of 111 from D-[ l-I4C]ribose and a secondary amine.232 3-Hydroxy-2-methyl-4H-pyran-4-one (maltol) and 2-acetyl-3-hydroxyfuran (isomaltol) are also products of the Maillard reaction.227Both have a considerable history, due to their early detection in beer and breads. A mechanism based upon the pyranose form of a methyl-a-dicarbonyl inter(232) H. G. Peer, G. A. M. van den Ouweiand, and C. N . deGroot, R e d . Trau. Chim. PaysBas, 87 (1968) 101 1-1016. (233) K . B. Hicks, D. W. Hams, M. S . Feather, and R. N. Loeppky, J . Agric. Food Chem., 22 (1974) 724-725. (234) K . B. Hicks and M. S. Feather, J . Agric. Food Chem., 23 (1975) 957-960.

HIGH-TEMPERATURE TRANSFORMATION O F CARBOHYDRATES CHZNRR'

I c=o I

HOCH

I

HCOH

I

HCOH

I

C02H

-

CHZNRR'

CHZ

COH

COH

I

II

COH

I I HCOH I HCOH

COZH

112

SCHEME 22.-Mechanism

CH3

I1

1 I

C=O

,

-

I

c=o

I

C=O

I I

HCOH

HCOH

HCOH

HCOH

I

I CO,H

32 I

-co, -111

I

COZH

1l3 114 115 for the Formation of 4-Hydroxy-S-methyl-3(2H)-furanone.

mediate for maltol formation has been suggested.227Other products of the Maillard reaction, which apparently require a similar mechanism, include 4-hydroxy-S-methy1-3(2H)-furanone(lll),2,3-dihydro-3,5-dihydroxy-6methyl-4-pyranone, and a c e t y l f ~ r m o i nThe . ~ ~ ~reaction between L-lysine and D-glucose affords 2-furanmethanol and 2,3-dihydro-3,5-dihydroxy-6methyl-4-pyranone, as well as several pyrroles and D-fructose-L-lysine condensation products.2" 5-(Hydroxymethyl)-2-furaldehyde(11)and several pyrroles were detected236in the reaction mixture after D-glucose and butylamine were refluxed in aqeuous solution at 95". Several other non-nitrogenous products have been identified as products of the Maillard reaction. These include butanol, butanone, butanedione, and ~ e n t a n e - 2 , 3 - d i o n eas ~ ~well ~ ~ , ~as dihydroxyacetone, glyceraldehyde, and ~ - e r y t h r o s eObviously, .~~~ the same products are present after mild acidic or basic degradation of carbohydrates. Thus, the necessity of an amine or amino acid in the mechanism of their formation is uncertain. Dihydroxyacetone forms dimeric ketosylamines when it reacts with primary amines at low temperatures .238 However, the reaction of dihydroxyacetone with amino acids apparently generates pyruvaldehyde (23) as an intermediate for several products, including allomaltol (5-hydroxy2-methyl-4-pyranone). In contrast to other amino acids, glycine reacts with dihydroxyacetone to yield a preponderance of butanedione. (235) J. E. Hodge, F. D. Mills, and B. E. Fisher, Cereal Sci. Today, 17 (1972) 34-40. (236) F. Hayase and H. Kato, Agric. B i d . Chem., 49 (1985) 467-473. (236a) F. Hayase and H. Kato, in Ref. 178c, pp. 39-48. (236b) G. MacLeod and J. M. Ames, in Ref. 178c, pp. 263-272. (237) T. Severin, J. Hiebl, and H. Popp-Ginsbach, Z. Lebensm. Unters. Forsch., 178 (1984) 284-287. (238) K. Heyns, U. Sage, and H. Paulsen, Curbohydr. Res., 2 (1966) 328-337.

322

OLOF THEANDER AND DAVID A. NELSON

An effort has also been made to determine the structure of products providing coloration in the Maillard reaction prior to melanoidin formation. The reaction between D-xylose and isopropylamine in dilute acetic acid produced2392-(2-furfurylidene)-4-hydroxy-5-methyl-3(2H)-furanone (116). This highly chromophoric product can be produced by the combination of 2-furaldehyde and 4-hydroxy-5-methyl-3(2H)-furanone (111) in an aqueous solution containing isopropylammonium acetate."O The reaction between D-xylose and glycine at pH 6 , under reflux conditions, also prod u c e ~116. ~ ~ Other ] chromophoric analogs may be present, including 117,

@IH 117

118

because 116 can be readily condensed wit.. 2 - f ~ r a l d e h y d e.. ~chromo~~ phoric furfurylidene-P-pyranone (US), similar to the furanone 116, was isolated after D-xylose had been heated with glycine in aqueous methanol.242It was proposed that 118 could be formed in the manner suggested for the pyranone (120) obtained from D-glucose and glycine (see Scheme 23). Under acidic reaction conditions, N-substituted 1-arnino-l-deoxy-Dfructose (79) loses its amino component (see Scheme 17) to yield 39, which can form both 11 and 2-hydroxy-6-(hydroxymethyl)-3(2H,6H)-

b

Howcc -

-W

CH$H

'19

t

HO CW ,H )(O .

__+

"YF

0cy

H

O

M

~

C

H

\ / 39

SCHEME23.-Formation (239) (240) (241) (242)

11 120 of a Furfurylidene-P-pyranonein the Presence of Methanol.

T. Severin and U. Kronig, Chem. Mikrobiol. Technol. Lebensm., 1 (1972) 156-157. F. Ledl and T. Severin, 2. Lebensm. Unters. Forsch., 167 (1978) 410-413. H. E. Nursten and R. O'Reilly, in Ref. 178b, pp. 103-121. F. Ledl, J. Hiebl, and T. Severin, 2. Lebensm. Unters. Forsch., 177 (1983) 353-355.

HIGH-TEMPERATURE TRANSFORMATION O F CARBOHYDRATES

323

pyranone (119). Compounds 11 and 119 then condense together, to give 120.

V. CARBOHYDRATE TRANSFORMATION IN CHEMICAL PROCESSES, INCLUDING HUMUSFORMATION

In some chemical processes, including natural humus formation, nonenzymic carbohydrate transformation, in aqueous media, into noncarbohydrate products is important. Improvements can probably be made in the yield and economy of certain compounds, including furans and phenolics, from carbohydrates. These compounds can be sources for various technical products, such as solvents, pesticides, plastics and other polymers, liquid fuels, and asphalt substitutes. 2-Furaldehyde (5) is an example of a carbohydrate-based compound of technical importance for various products. A promising use of the related 5-(hydroxymethyl)-2-furaldehydethat saves up to 40% of the phenol in resins has been reported.243Some phenolic products discussed in this Chapter might also be useful compounds, if further research can improve their yields and processing. Production of liquid fuels and other product mixtures by thermal liquefaction, particularly from the abundant lignocellulosic biomass sources, is an interesting alternative to total gasification or fermentation processes. Further research in processes, and a better understanding of the chemical reactions involved, might improve yields and quality by lessening inevitable degradation and recombination of reactive intermediates formed during liquefaction. The liquefaction process has considerable relation to the important, but much slower, formation of humus from plant materials in Nature. Early studies of sphagnum mosses and peat samples of different ages strongly indicated that the humic part, increasing with age, mainly originated from carbohydrates2@and not from lignin or other polyphenolic components which amounted to only -1% in the original mosses.245However, lignin may be the more important source of humus during the humification of wood and other lignocellulosic sources. The dried mosses contain up to 85% of polysaccharides, with high contents of pentoses and uronic acids. Under slightly acidic conditions, pentoses and uronic acids are converted into enones and phenols, which readily react to form dark-colored polyacid mers. 246 The presence of very reactive ~-lyxo-5-hexosulopyranuronic (243) (244) (245) (246)

H. Kock, F. Kranse, R. Steffen, and H. U. Woelk, Staerke, 35 (1983) 304-313. 0. Theander, Acta G e m . Scand., 8 (1954) 989-1000. 9. Lindberg and 0. Theander, Acta Chem. Scand., 6 (1952) 311. 0. Theander, in S. S. Stivala, V. Cresenzi, and I. C. M. Dea (Eds.), Recent Deuelopments in Industrial Polysaccharides, Gordon and Breach Science Publishers, New York, 1987, pp. 50-61.

324

OLOF THEANDER AND DAVID A. NELSON TABLEI1 Accelerated Aging of Filter Papers Impregnated with Model Compounds" Model compoundb

Brightness (% Scan)

None Methyl p-D-glucoside Cellobiose 5-(Hydroxymethyl)-2-furaldehyde(11) D-Ghcuronic acid Reductic acid (47)

86.8 85.9 83.5 74.3 37.4 19.4

L? The model compounds were exposedz4 for 16 h at 80" to 80% relative humidity. Proportion: (1.8 mmol per mmol of cellulose.)

residues,247together with D-galacturonic acid, in mosses supports the proposed importance of carbohydrate transformation in natural humus formation processes.II8 The presence of amino compounds is also important in these transformations, both as catalysts for carbohydrate degradation and as contributors to the chemical constituents of the humus.248 Dark-brown, water-insoluble polymers analyzed as lignin by the conventional, gravimetric, sulfuric acid-lignin method were isolated in large amounts, in addition to low-molecular acyclic and heterocyclic compounds in the Maillard reaction-systems containing D-glucose-glycineZM and ~-glucose-rnethylamine~~~ at pH 4.5 and 96". In thermal food-processes, formation of the favorable aroma compounds from carbohydrate transformation is a positive factor, but formation of off-flavors by over-processing, the loss of valuable amino acids and proteins, and the browning reaction often occurring are unwanted. In various cellulose processes, color formation is also a problem, often with lignin as the main cause. However, it has also been shown that carbohydrate transformation, either via partial hydrolysis of polysaccharides or the peeling reaction, is a factor contributing to yellowing of cellulosic materials by aging.246This is particularly important for bleached products and in sulfate (kraft) pulping. Table I1 provides some examples from accelerated aging of filter papers impregnated with aqueous solutions (pH 5.5) of different model compounds .246 A nonreducing carbohydrate, such (247) T. J. Painter, Curbohydr. Res., 124 (1983)c18-c21. (248) L. M. Benzing-Purdie, M. V. Cheshire, B. L. Williams, G. P. Sparling, C. I. Ratcliffe, and J. A. Ripmeester, J . Agric. Food Chem., 34 (1986)170-176.

HIGH-TEMPERATURE TRANSFORMATION O F CARBOHYDRATES

325

TABLEI11 Treatment" of Cellulose"plus Additives under Sulfate-Pulping Conditions Additive

Brightness of resulting pulp (70scan)

None Milled wood lignin Birch xylan Spruce glucomannan

80.1 65.6 69.5 72.2

Cellulose, 4 parts, and additive, 1 part.

as methyl-p-D-glucoside, and a reducing glucosaccharide, such as cellobiose, have very little effect on the color formation. The major acid-conversion product from hexoses, namely, 5-(hydroxmethyl)-2-furaldehyde (ll), provides a significant contribution to the color, but the conversion products from D-glucuronic acid, particularly reductic acid (47) contribute considerably more color. Furthermore, enones and phenols formed by carbohydrate transformation yield dark-blue or black complexes in the presence of ferric ions. The effect of color production from carbohydrate transformation in an alkaline pulping process, such as kraft pulping, is illustrated in Table 111. Cotton linters, which originally had a brightness of 90.5%, were treated for 4 h at 180"with kraft liquor, with and without additives.246Brightness was measured on paper made from the resulting, washed pulp. Sulfur dioxide and hydrogen sulfite solutions are the major additives for the prevention of discoloration of foods, but these additives are also important in some pulping processes. The treatment of cotton linters under the conditions of sulfite pulping, pH 2.1-8.0 and 135-160", for 2 h alone or with addition of birch xylan, L-arabinose, or D-glucuronic acid, respectively,245effectively stopped color formation in all of these experiments. As a comparison, cotton linters, alone or with birch xylan, Larabinose, or D-glucuronic acid, respectively, were treated with acetate buffer, pH 4.5,for 2 h at 160". In these experiments, the brightness respectively decreased to 84.7, 50.4, 35.8, and 18.3%. Most likely, the color-stopping reaction noted in food processing or sulfite pulping occurs through the formation of sulfohexosuloses that are further transformed into heat-stable sulfonic acids. 13032493250

(249) B. Lindberg, J. Tanaka, and 0. Theander, Acta Chem. Scand., 18 (1964) 1164-1170. (250) 0. Theander, in Ref. 178a, pp. 471-476.

326

OLOF THEANDER AND DAVID A. NELSON

There has been an increasing interest in the utilization of renewable resources for producing ethanol and other fermentation products. Such lignocellulosic materials as straw, bagasse, and wood waste have been used as fermentation sources, in addition to materials rich in sucrose and starch. The lignocellulosic materials are much more difficult to fractionate and hydrolyze without losses of carbohydrates and incomplete hydrolysis. It is not within the scope of the present Chapter to discuss the considerable variation of pretreatment and hydrolysis procedures that are being examined in this field. However, it is generally impossible to avoid some degradation by acidic pretreatments, such as steaming, or by final acid hydrolysis. Thus, in particular, if these procedures involve the (more reactive) pentoses and uronic acid components from hemicellulose polysaccharides and pectins, the acidic procedures promote the formation of furans, enones, and phenolics that can lead to carbohydrate losses and browning. Furthermore, there is a risk of formation of inhibiting products in substantial concentrations that can disturb the following fermentation process. Catechols, for instance, are frequent carbohydrate transformation-products that react readily with proteins and are known enzyme inhibitors. Sucrose solutions that had been heated for up to 8 h at 121" had an inhibitory effect on a number of bacteria and yeasts.2s1It was also shown2'* that the antimicrobial activity formed in heated neutral solutions of D-glucose and D-fructose was the result of di- or trivalent phenols, several of which were the same as those previously isolated246from heattreated sugar solutions. Inhibition of bacterial growth by Maillard reaction-products has also been reported.253 ACKNOWLEDGMENTS The authors thank the U.S. Department of Energy, Office of Basic Energy Sciences, for support of this effort under contract DE-AC06-76RLO 1830, as well as the Northwest College and University Association for Science (NORCUS).

(251) D. C. Wilson and H. D. Brown, Food Techno/., 7 (1953) 250-256. (252) T. Suortti, Z . Lebensm. Unters. Forsch., 177 (1983) 94-96. (253) H. Einarsson, B. E. Snygg, and C. Eriksson, J . Agric. Food Chem., 31 (1983) 10431047.

ADVANCES IN CARBOHYDRATE CHEMISTRY AND BIOCHEMISTRY,

VOL. 46

ADDENDUM TO ARTICLE 3: REFERENCES PUBLISHED A m E R 1986 (ADDED AT PROOF STAGE)

BY KEVINB. HICKS GENERALAREA

SPECIFIC TOPIC AND REFERENCE Simple and complex carbohydrate~~~’ Laser-based refractive index det e c t o r ~ “Diol” , ~ ~ ~ silica gel phases,333Monoclonal antibodybased stationary phases334

Review articles Instrumentation and stationary phases Separations Neutral mono-and di-saccharides Ionic mono- and di-saccharides

Simple, neutral oligosaccharides Simple, ionic oligosaccharides

Kestoses and n y ~ t o s eFermen,~~~ tation-derived sugar Ascorbic acid-2-pho~phates,~~~ Sugar phosphates,338Inositol phosphate^^^^.^^^

Gluco-olig~saccharides,~~~~~~~~~ Polysialic turonic

Oligogalac-

(331) K. Kakehi and S. Honda, J. Chromatogr., 379 (1986) 27-55. (332) D. J. Bornhop, T. G. Nolan, and N. J. Dovichi, J. Chrornatogr., 384 (1987) 181-187. (333) M. Abbou and A.-M. Siouffi, J. Liq. Chromatogr., 10 (1987) 95-106. (334) J. Dakour, A. Lundblad, and D. Zopf, Anal. Eiochern., 161 (1987) 140-143. (335) P. C. Ivin and M. L. Clarke, J . Chromatogr., 408 (1987) 393-398. (336) R. A. Lazarus and J. L. Seymour, Anal. Eiochem., 157 (1986) 360-366. (337) G. L. Moore and R. M. Fishman, J . Chromatogr., 419 (1987) 95-102. (338) A. V. Smrcka and R. G. Jensen, Plant Physiol., 86 (1988) 615-618. (339) J. A. Shayman and D. M. BeMent, Eiochem. Eiophys. Res. Commun., 151 (1988) 114-122. (340) K. A. Wreggett and R. F. Irvine, Eiochem. J . , 245 (1987) 655-660. (341) G. Bonn, J. Chrornatogr., 387 (1987) 393-398. (342) K. Koizumi, T. Utamura, Y. Kubota, and S. Hizukuri, J. Chromatogr., 409 (1987) 396-403. (343) P. C. Hallenbeck, F. Yu, and F. A. Troy, Anal. Eiochem., 161 (1987) 181-186. (343a) K. B. Hicks and A. T. Hotchkiss, Jr., J. Chrornatogr., 441 (1988) 382-386. 327

328

KEVIN B. HICKS

Complex, neutral oligosaccharides Complex, ionic oligosaccharides Applications Analysis of food carbohydrates Analysis of carbohydrates in biomass conversion processes Compositional analysis of carbohydrate polymers Structural and sequence analysis of carbohydrates

Cyclic o l i g o ~ a c c h a r i d e s , ~ ~ ~ - ~ ~ ~ ~ ~ ~ N-linked o l i g o s a ~ c h a r i d e s , ~ ~ ~ J ~ ~ Heparin fragments349

Nanogram detection of sugars,35o L a c t ~ l o s ePectins343a ,~~~ Sugars, oligosaccharides, and degradation p r o d ~ ~ t s , ~ ~ ~ , ~ ~ Pectins343a Proteoglycan-derived carbohyd r a t e ~Lipopolysac,~~~ ~ h a r i d e sG, ~l y~c~o p r ~ t e i n s , ~ ~ ~ Food P o l y s a ~ c h a r i d e s ~ ~ ~ ~ ~ ~ ~ ~ N-Linked oligosa~charides,~~~~~~~ Degree of polymerization of neutral oligosaccharides,357 Degree of methylation and acetylation of pectin,358“High mannose” oligosa~charides~~~

(344) M. Benincasa, G. P. Cartoni, F. Coccioli, R. Rizzo, and L. P. T. M. Zevenhuizen, J. Chromatogr., 393 (1987) 263-271. (345) H. W. Frijlink, J. Visser, and B. F. H. Drenth, J. Chromatogr., 415 (1987) 325-333. (346) K. Koizumi, Y. Kubota, T. Utamura, and S. Horiyama, J. Chromatogr., 368 (1986) 329-337. (347) S . Hirani, R. J. Bernasconi, and J. R. Rasmussen, Anal. Eiochem., 162 (1987) 485492. (348) N. Tomiya, M. Kurono, H. Ishihara, S. Tejima, S. Endo, Y. Arata, and N. Takahashi, Anal. Biochem., 163 (1987) 489-499. (349) Y. Guo and H. E. Conrad, Anal. Eiochem., 168 (1988) 54-62. (350) R. A. Femia and R. Weinberger, J . Chromatogr., 402 (1987) 127-134. (351) I. Martinez-Castro, M. M. Calvo, and A. Olano, Chromatographia, 23 (1987) 132136. (352) E. Burtscher, 0. Bobleter, W. Schwald, R. Conch, and H. Binder, J . Chromatogr., 390 (1987) 401-412. (353) A. G . J. Voragen, H. A. Schols, M. F. Searle-Van Leeuwen, G. Beldman, and F. M. Rombouts, J. Chromatogr., 370 (1986) 113-120. (354) L. S. Lohmander, Anal. Eiochem., 154 (1986) 75-84. (355) I. W. Sutherland and A. F. D. Kennedy, Appl. Enuiron. Microbiol., 52 (1986) 948950. (356) M. Takeuchi, S. Takasaki, N. Inoue, and A. Kobata, J. Chromatogr., 400 (1987) 207-2 13. (357) M. Takagi, Y.Daido, and N. Morita, Anal. Sci., 2 (1986) 281-285. (358) A. G. J. Voragen, H. A. Schols, and W. Pilnik, Food Hydrocolloids, 1 (1986) 65-70. (359) S. Natsuka, S. Hase, and T. Ikenaka, Anal. Biochem., 167 (1987) 154-159.

ADDENDUM TO ARTICLE 3

Preparative I.c.

Special aspects Detectability and accuracy Post-column detection methods

Pre-column derivatives Combined I.c. techniques Future trends

329

14C-Labeledoligosaccharides, sugars, and sugar degradation products,341T r e h a l u l ~ s eGen,~~~ eral methods for mono- and disaccharides and sugar acids,361 Kestoses and n y ~ t o s e , ~Chitin ” oligosa~charides~~~ Laser-based refractive index det e c t ~ ~ -Cuprammonium ,~~* reagent ,333,363 4-Aminobenzoic acid reagent,350Indirect detection methods for cyclodexand sugar phosphates338 Reversible derivatization using 2amin~-pyridine~~ Direct coupling of 1.c. to f.a.b.m.s. for analysis of oligosaccharides365-367 Capillary I.c. of sugars,332Affinity separations of oligosaccharide~~~~

(360) D. Cookson, P. S. J. Cheetham, and E. B. Rathbone, J. Chromatogr., 402 (1987) 265-272. (361) K. B. Hicks, S. M. Sondey, and L. W. Doner, Carbohydr. Res., 168 (1987) 33-45. (362) K. B. Hicks, Methods Enzymol., 161B (1988) 410-416. (363) D. B. McKay, G. P. Tanner, D. J. Maclean, and K. J. Scott, Anal. Eiochem., 165 (1987) 392-398. (364) G. R. Her, S. Santikam, V. N. Reinhold, and J. C. Williams, J . Carbohydr. Chem., 6 (1987) 129-139. (365) P. Boulenguer, Y. Leroy, J. M. Alonso, J. Montreuil, G. Ricart, C. Colbert, D. Duquet, C. Dewaele, and B. Fournet, Anal. Eiochem., 168 (1988) 164-170. (366) Y. Ito, T. Takeuchi, D. Ishii, M. Goto, and T. Mizuno, J. Chromatogr., 391 (1987) 296-302. (367) S. Santikam, G. R. Her, and V. N. Reinhold, J . Carbohydr. Chem., 6 (1987) 141154.

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ADVANCES IN CARBOHYDRATE CHEMISTRY AND BIOCHEMISTRY, VOL. 46

ADDENDUM TO ARTICLE 4

BY RENB CSUKA N D BRIGETTEI. GLANZER Additional n.m.r.-spectral data have been become available since about mid-1986. Further data for hexopyranosyl fluoride^,'^^^^ as well as for 2deoxy-2-fluoro-hexopyranoses and -hexopyranosides,200-2'0 have been reported by several groups, whereas only a few articles dealt with pentopyranose2@'or hexo(or pento)furanose analogs2@'*211 of these compounds. or C-4,213as well as at Monosaccharides fluorinated at C-3207,209,212 (193) I. P. Street and S. G. Withers, Can. J . Chem., 64 (1986) 1400-1403. (194) J. Thiem and M. Wiesner, Synthesis, (1988) 124-127. (195) S. J. F. Macdonald and T. C. McKenzie, Tetrahedron Lett., (1988) 1363-1366. (196) J. Thiem, M. Kreuzer, W. Fritsche-Lang, and H.-M. Deger, Ger. Offen. DE3528654A1 (1987). (197) P. KovBC, H. J. C. Yeh, G. L. Jung, and C. P. J. Glaudemans, J. Carbohydr. Chem., 5 (1986) 497-512. (198) M. Kreuzer and J. Thiem, Carbohydr. Res., 149 (1986) 347-361. (199) P. KovBC, H. J. C. Yeh, and G. L. Jung, J . Curbohydr. Chem., 6 (1987) 423-439. (200) K. Dax, B. I. Glanzer, G. Schulz, and H., Vyplel, Carbohydr. Res., 162 (1987) 13-22. (201) M. Tada, T. Matsuzawa, K. Yamaguchi, Y.Abe, H. Fukuda, M. Itoh, H. Sugiyama, T. Ido, and T. Takahashi, Carbohydr. Res., 161 (1987) 314-317. (202) R. W. Binkley, M. G. Ambrose, and D. G. Hehemann, J . Carbohydr. Chem., 6 (1987) 203-2 19. (203) F. Oberdorfer, W. E. Hull, B. C. Traving, and W. Maier-Borst, Int. J . Radiat. Appl. Instrum., Purr A , 37 (1986) 695-701. (204) P. KovBC, Carbohydr. Res., 153 (1986) 168-170. (205) M. Diksic and D. Jolly, Carbohydr. Res., 153 (1986) 17-24. (206) P. Di Raddo and M. Diksic, Curbohydr. Res., 153 (1986) 141-145. (207) P. KovBC, H. C. Yeh, and C. P. J. Glaudernans, Carbohydr. Res., 169 (1987) 23-34. (208) W. A. Szarek, G. W. Hay, B. Doboszewski, and M. M. Perlmutter, Carbohydr. Res., 155 (1986) 107-118. (209) B. Doboszewski, G. W. Hay, and W. A. Szarek, Can. J . Chem., 65 (1987) 412-419. (210) A. Luxen, N. Satyamurthy, G. T. Bida, and J . R. Barrio, I n t . J . Rudiar. Appl. Instrum., Purr A , 37 (1986) 409-413. (211) H. G. Howell, P. R. Brodfuehrer, S. P. Brundidge, D. A. Benigni, and C. Sapino, Jr., J. Org. Chem., 53 (1988) 85-88. (212) G. W. J. Fleet, J. C. Son, and A. E. Derome, Tetrahedron, 44 (1988) 625-636. (213) F. Latif, A. Malik, and W. Voelter, Justus Liebigs Ann. Chem., (1987) 617-620. 33 1 Copyright 8 1988 by Academic Press, Inc. All rights of reproduction in any form reserved.

332

RENE CSUK AND BRIGETTE I. GLANZER

C-6,20932'4 anhydro sugars,199,208~215~216 branched monosaccharide^,^^^ fluorinated amino sugars,194,218-225 difluorinated monosaccharide^,'^^,^^^^^"^^^ and fluorinated monosaccharide phosphates,23b234and p h o ~ p h o n a t e s ~ ~ ~ have been described. Further progress has been achieved in the synthesis and n.m.r.-spectral analysis of fluorinated avermectin B1,,236tylonolide.237and neuraminic acid (214) J. R. Durrwachter, D. G. Drueckhammer, K. Nozaki, H. M. Sweers, and C.-H. Wong, J. Am. Chem. Soc., 108 (1986) 7812-7818. (215) J. Doleialovfi, M. Cerng, T. Tmka, and J. Pacfik, Collect. Czech. Chem. Commun., 41 (1976) 1944-1953. (216) D. J. Baillargeon and G. S. Reddy, Carbohydr. Res., 154 (1986) 275-279. (217) K. Bischofberger, R. H. Hall, A. Jordaan, and G. R. Woolard, S. Afr. J. Chem., 33 (1980) 92-94. (218) C. Bosso, J. Defaye, A. Domard, A. Gadelle, and C. Pedersen, Carbohydr. Res., 156 (1986) 57-68. (219) R. L. Thomas, S . A. Abbas, C. F. Piskorz, and K. L. Matta, Carbohydr. Res., 175 (1988) 158-162. (220) R. L. Thomas, S. A. Abbas, and K. L. Matta, Carbohydr. Res., 175 (1988) 153-157. (221) D. Picq, I. Drivas, G. Carret, and D. Anker, Tetrahedron, 41 (1985) 2681-2690. (222) M. Sharma, G. G. Potti, 0. D. Simmons, and W. Korytnyk, Carbohydr. Res., 163 (1987) 41-51. (223) R. Faghih, F. C. Escribano, S. Castillon, J. Garcia, G. Lukacs, A. Olesker, and T. T. Thang, J . Org. Chem., 51 (1986) 4558-4564. (224) L. H. B. Baptistella, A. J. Marsaioli, P. M. Imamura, S. Castillon, A. Olesker, and G. Lukacs, Carbohydr. Res., 152 (1986) 310-315. (225) D. Picq and D. Anker, Carbohydr. Res., 166 (1987) 309-313. (226) J. P. Praly and G. Descotes, Tetrahedron Lett., (1987) 1405-1408. (227) S.-H. An and M. Bobek, Tetrahedron Lett., (1986) 3219-3222. (228) Y. Hanzawa, K. Inazawa, A. Kon, H. Aoki, and Y. Kobayashi, Tetrahedron Lett., (1987) 659-662. (229) A. Dessinges, F. C. Escribano, G. Lukacs, A. Olesker, and T. T. Thang, J. Org. Chem., 52 (1987) 1633-1634. (230) P. Le Markchal, C. Froussios, and R. Azerad, Biochimie, 68 (1986) 1211-1215. (231) E. M. Bessell and P. Thomas, Biochem. J . , 131 (1973) 77-82. (232) T. Nakada, I. L. Kwee, G. A. Rao, and C. B. Conboy, Biochem. Arch., 1 (1985) 163166. (233) T. Nakada and I. L. Kwee, Biochem. Arch., 2 (1986) 53-61. (234) S. G. Withers, D. J. MacLennan, and I. P. Street, Carbohydr. Res., 154 (1986) 127144. (235) G. M. Blackburn and M. J. Parratt, J . Chem. Soc., Perkin Trans. 1 , (1986) 1425-1430. (236) C. Bliard, F. C. Escribano, G. Lukacs, A. Olesker, and P. Sarda, J. Chem. Soc., Chem. Commun.. (1987) 368-370. (237) S. Kageyama, T. Onoda, T. Tsuchiya, S. Umezawa, and H. Umezawa, Carbohydr. Res., 169 (1987) 241-246. (238) K. Okamoto, T. Kondo, and T. Goto, Bull. Chem. Soc. J p n . , 60 (1987) 631-636. (239) M. Imoto, N. Kusunose, Y. Matsuura, S. Kusumoto, and T. Shiba, Tetrahedron Lett., (1987) 6277-6280. (240) M. Sharma, C. R. Petrie, IIIrd, and W. Korytnyk, Carbohydr. Res., 175 (1988) 25-34.

ADVANCES IN CARBOHYDRATE CHEMISTRY AND BIOCHEMISTRY, VOL. 46

ADDENDUM TO ARTICLE 6 BY RONALD J. CLARKE, JOHNH. COATES,AND STEPHENF. LINCOLN In this Addendum, reference will be made to a selection of publications in order to indicate current trends to readers. (a).-Preparation of cyclodextrin derivatives; substitution at a secondary hydroxyl group of the cyclodextrin annulus. Murakami and cowora new and convenient method for the regioselective k e r ~ described ’~~ tosylation of the 2-hydroxyl groups of alpha, beta, and gamma cyclodextrin by means of a cyclic tin intermediate. The method is based on the reaction of dibutyltin oxide with 1 ,2-diols to form five-membered dibutylstannylidene derivatives. Useful yields of the 2-0-tosyl derivatives of the cyclodextrins were obtained. (b).-Kinetic studies of the mechanism of complex-formation between alpha cyclodextrin and a series of hydroxyphenylazo derivatives of naph’ ~ ~ out an extensive, thalenesulfonic acids. Yoshida and F ~ j i m o t ocarried stopped-flow, kinetic study of a series of five of the aforementioned compounds, modified by substitution with groups of various charges and sizes, interacting with alpha cyclodextrin under pH conditions where the phenolic OH group was undissociated. These experiments were then repeated under pH conditions where the phenolic OH groups were ionized. The results were interpreted in terms of an “associative interchange” mechanism. An intermediate species was postulated, with its formation involving included water being displaced from the cyclodextrin cavity and partial collapse of the water structure around the incipient guest. Changes of slope of the Arrhenius plots for the forward rate-constants of the reactions of the phenolate species were interpreted in terms of structural changes of the reactants, or changes of the rate-determining steps in the lower-temperature range of the reactions investigated, or both. (c).-Fluorescence enhancement by means of cyclodextrin inclusion complexes. This has been examined by several groups of workers in a (183) T. Murakami, K. Harata, and S. Morimoto, Tetrahedron Lett., (1987) 321-324. (184) N . Yoshida and M. Fujimoto, J . Phys. Chem., 91 (1987) 6691-6695.

333 Copyright 0 1988 by Academic Press, Inc. All rights of reproduction in any form reserved.

334 RONALD J. CLARKE, JOHN H. COATES, AND STEPHEN F. LINCOLN

variety of systems. Kano and coworker^^^^ studied the binding sites of pyrene and related compounds, and chiral excimer formation, within the cavities both of cyclodextrins and branched cyclodextrins. Using circular dichroism and circularly polarized fluorescence, they showed that the dimer of pyrene that was included within gamma cyclodextrin had lefthanded chirality, whereas the 1,3-dinaphthylpropane dimer had righthanded chirality when included therein. These dimers were believed to be bonded to the relatively hydrophobic, primary-hydroxyl side of the cyclodextrin annulus, because the analogous pyrene dimer formed in the 6-0a-maltosyl-gamma cyclodextrin cavity (that was capped on the primary hydroxyl side) exhibited right-handed chirality. Agbaria and GillIa6studied excimer fluorescence arising from extended 2,5-diphenyloxazole-gamma cyclodextrin aggregates, in which the inclusion of pairs of phenyl groups from different 2,S-diphenyloxazole (PPO) molecules within a common gamma cyclodextrin annulus resulted in both excimer fluorescence and the formation of a staggered, linear array of PPO molecules linked by phenyl groups overlapping within gamma cyclodextrin molecules. The use of cyclodextrins to enhance the fluorescence of fluorophores used in analytical procedures is exemplified in an article by Sanchez and coworkers. The ligand, benzyl 2-pyridyl ketone-2-pyridyl hydrazone may be used in a fluorescence assay for gallium. They found that, when this ligand was used in the presence of beta cyclodextrin, the fluorescence observed was linear over the gallium concentration range of 0.8-800 ng-mL-', with very much increased selectivity against competing cations. Presumably, the increased selectivity can be ascribed to the steric constraints imposed on the ligand by inclusion within the beta cyclodextrin annulus. (4.-Studies of the diastereomeric complexes formed between cyclodextrin molecules and chiral molecules. Harata and coworkersIE8determined the crystal structures of the inclusion complexes of (S)- and ( R ) mandelic acid with hexakis(2,3,6-tri-O-methyl)-alphacyclodextrin. The crystal structures showed that an induced conformational change in the alpha cyclodextrin molecule resulted in distinctly different geometry for each of the diastereoisomers. (185) K. Kano, H. Matsumoto, Y. Yoshimura, and S. Hashimoto, J . Am. Chem. SOC.,110 (1988) 204-209. (186) R. A. Agbaria and D. Gill, J . Phys. Chem., 92 (1988) 1052-1055. (187) F. G . Sanchez, M. H. Lopez, and J. C. M. Gomez, Fresenius Z . Anal. Chem., 328 (1987) 499-500. (188) K. Harata, K. Uekama, M. Otagiri, and F. Hirayama, Bull. Chem. SOC. J p n . , 60 (1987) 497-502.

ADDENDUM TO ARTICLE 6

335

The inclusion modes of flurbiprofen with beta cyclodextrin and with heptakis(2,3 ,ti-tri-O-methyl)-beta cyclodextrin have been studied by Imai and coworkers.lS9 They showed that, although the Cotton effects in the circular dichroic spectra induced by beta cyclodextrin in R ( - ) and S ( + ) flurbiprofen are identical, those induced by heptakis(2,3,6-tri-O-methyl)beta cyclodextrin differ from each other and from those induced by beta cyclodextrin. C.p.-m.a.s. 13C-n.m.r. experiments showed that the cyclodextrin ring is probably more distorted in the flurbiprofen inclusion complex with methylated beta cyclodextrin than in that with beta cyclodextrin. (el.-The use of cyclodextrins bonded to solid supports as chromatographic media for the resolution of isomers and of enantiomers. This is becoming quite widespread (see, for example, a review by ArmstrongIgo). Alpha cyclodextrin molecules bonded to silica beads (5 p m diam.) by seven-atom-long, ether-linkage-containing, polymethylene spacergroupsI9l have been used to separate a number of racemic compounds into their constituent enantiomers, including racemic tryptophan, phenylalanine, and tyrosine. Similar materials incorporating beta instead of alpha cyclodextrin have been used to separate the optical isomers of scopolamine, cocaine, homatropine, and atropine. 192 ( f ) . - A novel application of cyclodextrins in liquid membranes. This has been demonstrated by Armstrong and Jin.193Enantiomeric o r isomeric enrichment was shown to occur when racemic mixtures, or mixtures of isomers, were allowed to diffuse from a nonaqueous phase through an aqueous liquid membrane containing a dissolved cyclodextrin into a second nonaqueous phase. The degrees of enrichment were considered to be encouraging, and it was foreshadowed that efforts will be made to develop this method for practical separations of enantiomers and of isomers in the future.

(189) T. Imai, M. Otagiri, H. SaitB, and K. Uekarna, Chem. Phurm. Bull., 36 (1988) 354359. (190) D. W. Armstrong, Anal. Chem., 59 (1987) 84A-91A. (191) D. W. Armstrong, X. Yang, S. M. Han, and R. A. Menges, Anal. Chem., 59 (1987) 2594-2596. (192) D. W. Armstrong, S. M. Han, and Y. 1. Han, Anal. Biochem., 167 (1987) 261-264. (193) D. W . Armstrong and H. L. Jin, Anal. Chem., 59 (1987) 2237-2241.

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AUTHOR INDEX Numbers in parentheses are footnote reference numbers and indicate that an author’s work is referred to although his name is not cited in the text. Armstrong, D. W., 233, 248 Ashoor, S. H.,307 Aso, K., 307

A Abad, A., 194 Abbot, S. R., 24, 38(37) Abe, J.-I., 247(170b), 248 Abraharnsson, B., 303 Abusabah, E. K. E., 62(279), 63 Acevedo, 0. L., 28 Ackerman, J. L., 86(59), 87(59), 89 Acton, E. M., 159 Adam, M. J., 86(48), 89, 104(48), 142(48), 143(48) Adamson, J., 76, 80, 89, 146(168), 147, 151 Ahderinne, R., 36 Aitzetmuller, K., 23, 38, 52(31) Akhrem, A. A., 159 Albano, E. L., 104(98), 105, 143(98), 155(98) Albericio, F., 199 Albersheim, P., 20, 40, 41, 42, 54, 57, 59(165), 60(165), 262, 264 Albert, R., 100, 116, 152(125), 158(125), 166(91), 167(91), 170(91, 125), 175(129, 177(125) Alfiildi, J., 306 Alfredsson, B., 291, 294 Alpenfels, W. F., 267 Aman, P., 57, 306 Ambrose, M. G., 95(86), 97 Amit, B., 179, 181, 184, 188(1), 193, 198(58), 202, 203 Anderegg, P., 290 Anderson, A. W., 34, 39, 54(150) Anderson, D. M. W., 288 Anderson, S., 34 Anderson, R., 291 Anet, E. F. L. J., 284, 286, 309 Angyal, S. J., 25, 26 Anker, D., 117(129), 118, 119, 128(129) Annison, G., 54 Anteunis, M.,95(83), 97, 106 Antonopoulos, C. A., 37, 5 5 , 60(130), 65(253) Appell, H. R., 274 Arad-Yellin, R., 209

B Baenziger, J. U., 42, 45, 46, 48(193), 60(168) Baer, H. H., 119(133), 120, 123(133), 124(133), 125(133), 127(133), 170(133), 171(133), 308 Baker, J. O., 57, 70(267a) Ballardie, F. W., 117, 118(128) Ballou, C. E., 270 Baptistella, L. H. B., 119(132), 120, 123(132), 124(132), 125(132), 127(132), 170(132), 171(132) Barbalat-Rey, F., 80, 140(37), 141, 155 Barford, A. D., 75, 86(12), 90(12), 91(12), 93(12), 94, 95(12), 148(12) Barker, H. M., 67 Barker, P. E., 62(278), 63 Barker, S. A., 25, 39(44) Barltrop, J. A., 198 Bamett, J. E. G., 152 B a t h , H. G., 67, 68(290, 291), 69 Bartholomew, D. G., 181, 182(13) Barton, D. H. R., 200 Batley, M., 68 Baudisch, O., 293 Bauman, W.C., 24 Baust, J. G., 19, 21, 23(9), 24, 32(39), 33(39), 41(39), 59(39), 60(39), 64(39) Bax, A., 74 Bayley, H.,204 Beebe, J. M., 51 Bell, R. H.,180, 189(6) BeMiller, J. N., 182, 251, 292, 296, 297, 301 Bender, H., 44 Bender, M. L., 206, 221(92), 222, 223, 227(2), 244, 245, 248 Ben-Efraim, D., 202 Bennek, J. A., 271 Benschop, H. P., 248

137

338

AUTHOR INDEX

Benzing-Purdie, L. M., 307, 325 BOOS,K.-S., 31 Bergeron, R. J., 206, 230, 23 I , 245( 122) Borchert, W., 214 Bergh, M. L. E., 33, 42, 43(88), 45, 46, Borgegrain, R.-A., 191 65(170) Bouquelet, S., 45 Bergius, F., 274, 298 Bradford, A . D., 191 Bergmann, E. D., 144 Brandange, S., 172(189), 173 Berl, E., 274 Brandes, W. B., 51, 64(233) Bernasconi, C. F., 241 Brandon, R. E., 300 Bernhard, R. A . , 317 Braunovh, M., 151(175), 152 Berry, R. E., 311 Breebaart-Hansen, J. C. A. E., 222, 227, Bessell, E. M., 95(84), 97, 148(84), 149(84) 248 Bethell, G. S., 25 Brereton, I. M., 239 Betzel, C., 227, 228(111) Breslow, R.,206, 208, 210, 244 Beveridge, R. J., 25 Breuer, H . , 309 Bhacca, N. S., 75, 79(17), 80(17), 82(17), Briggner, L.-E., 210 83(17), 84(17) Brimacombe, J. S., 90(67, 68), 91(72), 92, Bida, G. T., 86(55), 87(55), 89, 146(167), 99(67, 72), I14(72) 147 Brink, A . J., 138(156), 139(156), 140, Bienkowski, M. J., 48, 62(216) 141(156), l42( 156) Biermann, C. J., 261 Brinkman, U. A. T., 67, 68 Binder, H., 23 Brobst, K. M., 25, 51 Binkley, R. W., 95(86), 97, 179, 180(3), 191 Brodfuehrer, P. R.,110(110), 111, 138(110) Birks, J. B., 209 Broido, A . , 274 Birks, J. W., 67 Brondz, I., 258 Birr, C., 192, 193 Brons, C., 24, 51(38), 52(38), 64(38) Bisehofberger, K., 139(157), 140, 142(157) Broom, A. D., 181, 182(13) Bishop, E. D., 74 Brose, K. H., 319 Blackburne, I. D., 113, 135(117) Broser, W., 218, 219(79), 232 Blair, M. G., 282 Brown, H. D., 326 Blake, J. D., 34 Brown, R. D., Jr., 39, 54 Blakeney, A. B., 263, 264(34) Briiller, W., 39 Blanken, W. M., 33 Brunngraber, E. G., 93(77), 94, 96(77), Blankenhorn, G., 307, 319(183) 149(77), 150(77), 151, 165(77), 175(77) Blaschek, W., 52, 53(244) Brunt, K., 21, 27(23), 36 Blomquist, G., 213, 296 Bryn, K., 258, 259(17) Bloor, D., 238(144) Buchberger, W., 65 Blumberg, K., 29 Buckee, G. K., 51 Bobleter, O., 26, 52, 53, 66(247), 298, 300 BuddSinskL, M., 144, 173(161) Bobrov, P. A , , 299 Bueno, M. P., 51 Bochkov, A. F., 251 Burns, I. W., 21, 23(26) Bociek, S. M., 231, 233(122a) Burtscher, E., 26, 53(54) Bock, K., 77, 78(28), 97(87), 98, 107(107), Bush, C. A., 29, 42, 43(174), 59(174) 108(107), 109, 134, 137, 138, 166(25), Butchard, C. G., 104(99), 105, 132(148, 168(107), 169(107) 149), 133, 153(148, 149) Boehm, J. C., 28 Bystrom, K., 233 Boersma, A . , 42, 43(171), 46, 59(199), 61 Bolt, J. D., 235 C Bonenfant, A. P., 112, 154(178), 155, 169(114) Callaert-Deveen, B., 68 Bonn, G., 20, 26, 39(13), 53, 54, 66(247) Cama, L. D., 191, 198(41)

AUTHOR INDEX Campbell, J. C., 129(141), 130(141), 131, 135(141) Cantor, S. M., 286 Capon, B., 117, 118(128), 251 Caputo, A. G., 38 Card, P. J., 74, 77, 92, 93(92), 94(92), 96(27), 100(65), 106(65), I19(65), 120(65), 122(65), 144, 149(65), 150(27), 162(65), 163(65), 164(65), 165(27), 168(65), 171(65), 173(166), 175(27) Cardelino, B., 221(90), 222, 225(90) Cardon, P., 46 Cam, P. W., 72 Carr, S. A., 56, 69 Castillon, S., 117, I18(127), 119(127), 120, l23( l27), 124(127), 1 2 3l27), l26( l27), 170(l27), I7 I ( 127) Casu, B., 233, 245(127) Catala, F., 277 Cavalier, J. C., 274 Cerny, M., 87(62), 89, 92, 114(73), 144, 145, 152, 159(73), 173(161) Chamberlin, J. W., 192 Chambers, R. E., 256, 258(10) Chan, L., 21, 61(28) Chang, C.-D., 191 Channing, M. A,, 231 Chaplin, M. F., 258 Chavis, C., 308 Cheetham, N. W. H., 19, 21, 29, 32(5), 33, 39(29), 41, 54, 62(19), 63, 256, 257(12) Chekkor, A., 45 Cheng, J. C.-Y., 28 Cheshire, M. V., 325 Chester, T. L., 71 Chin, T.-F., 208, 219(13) Chornet, E., 274 Chow, Y. L., 200 Christensen, B. G., 191, 198(41) Chung, C., 235 Churms, S. C., 18, 72(1) Ciamician, E., 181 CieSlik, E., 317 Cifonelli, J. A,, 275 Cifonelli, M., 275 Ciner-Doruk, M., 311 Claessens, H. A , , 29, 39(64), 59(64), 70(64) Clamp, J. R., 256, 258(lO) Clamp, P. I., 42, 57(167), 60(167) Clarke, M. L., 34, 35(98)

339

Clarke, R. J., 209(37), 210, 234(37, 38). 242(37, 38). 244(37, 38, 39) Clermont, L. P., 298 Clowes, G. A., 244 Coates, J. H., 209(37, 38, 39), 210, 234, 239, 242(37, 38), 244(37, 38, 39), 245(140) Codington, J. F., 104(102), I05 Cohen, A., 283 Coleman, G. H., 300 Coles, E., 56, 69 Collings, G. F., 264 Collins, P. M., 188, 189(38, 39) Colonna, S., 95(82), 96, 99(82) Comin, J. H., 13 Conchie, J., 48, 270 Connors, K. A., 220, 227, 232(85), 239 Conrad, H. E., 48, 54, 5 5 , 62(216) Cook, J. C., 70 Corbett, W. M., 301, 305 Corran, P. H., 38 Costello, D. E., 42 Couperwhite, I., 54 Covey, T. R., 69, 70(318) Cox, A., 200 Coxon, B., 102(96), 103 Cramer, F., 206, 208(1), 209, 214, 215, 217, 219(16), 221(16), 233, 234(16), 235(16), 239(16), 244 Cromwell, W. C., 233 Crowther, J. B., 69, 70(318) Csuk, R., 98, 115, 166(89a) Cummings, L., 25, 30(46) Cushley, R. J., 104(102), 105 Czerlinski, G. H., 241

D Dacons, J. C., 296 Dahlin, C. E., 46 Dahlman, O., 172(189), 173 D’Amboise, M., 23, 67(34) Damon, C. E., 51 Daniel, P. F., 68 Darvill, A. G., 29, 42, 49(63), 54, 57 Das, P. K., 183 Date, Y.,226 Davidson, G. F., 301 Davis, H. F., 183 Davis, M. A. F., 40

340

AUTHOR INDEX

Davis, W. A., 50 Dawson, R., 67 Dax, K., 86(49), 89, 93(49), 99(49), 100, 104(49), 111(49), 116, 161(49), 162(49), 166(91), 167(49, 91), 168(49), 169(49), 170(91) Day, W. R., 29, 39(60), 60(60),70(60) de Bruijn, J. M., 292 De Bryn, A., 95(83), 97, 106 Defaye, J., 277 De Feudis, D. F., 68 de Gourcy, C., 308 de Groot, C. N., 320 De Jongh, R. D., 203 Delaney, S. R., 37, 48, 55 Dell, A., 44,70 Demarco, P. V., 218 Demmit, T. F., 273 Descotes, G., 134(153), 135, 190 Dessinges, A., 87(61), 88(61), 89, 117, 118(127), 119(127), 120, 123(127), 124(127), 125(127), 126(127), 170(127), 171(127) Dethy, J.-M., 68 Deuel, H., 288, 293 Deulofeu, V., If, 13 De Villiers, 0. G., 138(156), 139(156), 140, 141(156), 142(156) Dewaele, C., 58, 61(275) Diaz, S., 36 Dick, J., 66 Dietsche, W., 248 Dijkgraaf, P. J. M., 34, 35(99) Diksic, M., 85(47), 86(47), 87(47), 89 D i r k , J. M. H., 34 Dixon, H.B. F., 307, 319(183) Dmytraczenko, A., 191 DoleZ6lova, J., 92, 114(73), 144, 159(73), 173(161) Donaldson, B., 76, 92(19), 148(19) Doner, L. W., 33, 35, 51, 63(241) Donovan, J., 274 Dorland, L., 42, 43, 46(172), 79 Drabowicz, J., 248 Drauz, K., 317 Dreux, M., 66 Dreyer, R. N., 61 Drueckhammer, D. G., 90(66),91(66), 92, 99(66), 109(66), 11N66) Dryselius, E., 300

D’Souza, V. T., 245 Dua, V. K., 29, 42, 43(174), 44, 47(62), 48(62), 59(61), 60(61, 62), 65(61) Duang, E., 35 Dudman, W., 57, 259 Durham, D. G., 288 Dwek, R. A., 86(54), 89, 92, %(53), 99(53), 104(53), 105, 112(53), 131, 133, 146(53), 155(53), 156(53)

E Eastman, J. F., 291 Eaton, D. F., 209 Ebringerovh, A., 306, 321(174) Eby, R., 177 Egge, H., 44 Eggert, F. M., 56, 68(263), 267 Ehrenkaufer, R. E., 86(56), 87(56), 89 Eichner, K., 311 Einarsson, H., 326 Ejima, S., 245 El Khadem, H. S., 295 Elliott, D. C., 274 Ellis, G. P., 307, 308 Ellmore, T. L., 269 Emert, J., 209 Enami, K., 67 Engels, J., 204 Engfeldt, B., 32(92), 33, 55, 56(92), 65(253) Enkvist, T., 283, 294 Epling, G. A., 194 Epshtein, Ya. A., 300 Erbing, B., 144(163), 145, 174(163) Eriksen, P. B., 48, 55(212), 57(212) Eriksson, C., 326 Escott, R. E. A., 67 Eswarakrishnan, S., 104(101), 105 Evans, W. L., 301 Evelyn, L., 95(81), 96, 100(81), 112(81), 113(81) Ewald, L., 213

F Faillard, H., 36 Faure, A., 190 Feast, A. A. J., 291 Feather, M. S., 275, 276, 277(22), 284(22), 285, 286, 288, 289, 291(22), 319, 320 Fedan, J. S., 204

AUTHOR INDEX Fedoroilko, M., 279 Feeney, R. E., 307, 319(183) Fengel, D., 298 Ferrier, R. J., 143, 172(159), 301 Fiedler, H., 36 Filby, W. G., 182 Finley. J. W., 35 Fishbein, L., 277 Fisher, B. E., 318, 320(227), 321 Fishman, M. L., 265 Fitt, L. E., 25, 39(50) Florkin, M., 207 Fodor, G., 309 Foltz, A. K., 50 Forbush, B., 204 Fors, S., 311 ForsskBhl, I., 282, 294(49), 295(49) Foster, A. B., 75, 76, 80, 83(41), 84(41), 85, 86(12), 87(58), 89, 90(12), 91(12), 92, 93(12), 94, 95(12), 97, 99(20), 105(11, 20), 112(20), 114(72), 146(18), 147, 148(11, 12), 149(84), 151, 155(11), 156, 191 Foster, J. F., 296 Foucault, A., 31 Fox, A., 266 Franken, H., 289 FranzCn, L.-E., 57 Freed, J. H., 20, 43, 47(16) Frei, R. W., 67, 68 French, D., 206, 214, 217, 220, 249 Freudenberg, K., 213, 214, 215, 217(70), 296 Friday, D., 24, 32(39), 33(39), 41(39), 59(39), 60(39), 64(39) Friedrich, E., 197 Froehlke, A. W., 298 Fu, Y. L., 274 Fujimaki, M., 313 Fujimoto, M.,234 Fujita, K.,245 Funasaka, W., 304 Fur6, I., 231 Furue, M., 239 Fyfe, C. A,, 219

G Gabel, C. A., 42 Gacesa, P., 33, 34(%), 54(%)

341

Galensa, R., 68 Galitzer, S. J., 51 Games, D. E., 69 Gandelman, M. S., 67 Garbutt, S., 288 Gardiner, D., 300 Carves, K.,298 Gaudemer, A., 75, 78(16), 79(16), 82(16) Geeraert, E., 21, 58(24), 61(24) Geigert, J., 34 Gelb, R. I., 221(88, 90, 91, 92), 222, 225(90), 239 Gentile, B., 112, 141, 169(114) Gerasimowicz, W. V., 226 Gibeily, G. J., 231 Gidley, M. J., 231, 233(122a) Giersch, C., 36 Gilpin, R. K.,51 Giralt, E., 199 Glad, M., 31, 72 Glanzer. B. I., 86(49), 87(49), 89, 93(49), 104(49), 111(49), 115, 161(49), 162(49), 167(49), 168(49), 169(49) Glaudemans, C. P. J., 77, 89, 92, 161(26), 162(186), 163, 164(26) Goldman, Y. E., 204 Golik, J., 57, 68(266) Golova, 0. P., 300 Goso, K., 44 Goto, M., 127(139), 128 Goto, R., 293 Gottschalk, A., 309 Goulding, R. W., 26, 70(53), 71(53) Govil, G., 73 Grangord, G., 301 Gravel, D., 195, 196(65) Gray, G. R., 271 Green, E. D., 46 Greene, T. W., 179 Grethlein, H. E., 300 Gridley, M. J., 40 Griffin, G . W., 183 Griffiths, D. W.,206, 227(2), 244(2) Griggs, L. E., 261, 267(23) Grimble, G. K.,67 Gross, B., 191 Griin, M.,35 Griinewald, K., 315 Guerrant, G.O., 267 Gum, E. K.,Jr., 39

AUTHOR INDEX

342

Giinther, H., 80 Gupta, D. V., 274 Gurjar, M. K., 123, 124(137), 125(137), 127(137) Gurr, E., 55 Gurwara, S. K., 199 Guthrie, R. D., 144(164), 145, 174(164) Gutsche, C. D., 284 Guyon, F., 31 H Haas, D. W., 303 Hacksell, U . , 28 Hadfield, A. F., 61 Hadziyev, D., 315 Hagedorn, M. L., 318 Hagemeier, E., 31 Haines, S. R.,98, 143, 166(89), 172(159) HalaSkovB, J., 145 Hald, L. H., 236 Hall, D., 234, 238(144) Hall, L. D., 74, 75, 76, 79, 80, 82(14, 15), 83(14), 85, 86(48), 89, 90(67), 92, 93(79), 94, 95(81), 96, 97, 99(67), 100, IOl(14, 32), 102(14, 32), 103, 106(104), 108(104), 109, 112(81), 113(81), I15(92), 129(34, 143), 130(34, 143, 144). 131, 142(48), 143(48), 146(18), 147, 148(84), 149(84), 173 Hall, M. A., 269 Hallen, R. T., 290, 316 Hamada, F., 246 Hamai, S., 209, 210(30), 243(30) Hammond, M., 244 Hanabusa, K., 245 Hanai, T., 39 Hands, C. H. G., 296 Hanes, C. S., 215 Haney, C. A,, 69 Hansch, C., 227 Hansen, L. D., 221(89), 222, 223(89) Hansson, L., 31, 72 Harada, A., 239 Harada, K., 31 Haradahira, T., 86(52), 89, 162(63) Harata, K., 209, 222, 249 Hardegger, E., 191 Hams, J. F., 275, 276, 277(22), 282, 284(22), 285, 286, 288, 289(74), 291(22), 320

Harris, P. J., 263, 264(34) Harrison, R., 159 Hart, G. W., 43, 47(182) Hartford, C. G., 50 Hase, S., 57, 68, 268, 270(49) Hasegawa, A., 127(139), 128 Hashimoto, Y., 107(105), 108(105), 109 Hassler, W., 25, 39(50) Hatt, B. W., 25, 39(44) Havinga, E., 203 Havlicek, J., 38 Hay, A. J., 48, 270 Hayami, J., 277, 291(34), 293 Hayase, F., 314, 321 Hayashi, M., 84(43), 85 Hayashi, T., 309 Heidt, L. H., 182 Hemminki, K., 28 Hems, R.,76, 83(41), 84(41), 85, 90(67), 91(20), 92, 93(78), 94, 99(20), 105(20), 112(20), 1 l4(72), 156 Henderson, D. E., 36, 67(118) Henderson, S. K., 36, 67(118) Hendrix, D. L., 19, 23(9), 24, 32(39), 33(39), 41(39), 59(39), 60(39), 64(39) Henglein, F. M., 233 Hennrich, N., 244 Herbert, J., 195, 196(65) Herbert, R. W., 288 Herbette, L., 204 Herchman, M., 187, 188 Herkstroeter, W. G., 243 Herscheid, J . D. M., 85, 86(39), 87(39), I13(39) Hersey, A., 234, 237(142), 238(142), 239( 142) Heyns, K., 309, 319, 321 Heyraud, A., 29, 32, 38, 39, 40(68), 57, 269 Hibberd, M. G., 204 Hibbert, H., 269 Hicks, K. B., 19, 23(7), 25, 33, 35, 51, 61(89), 62(89), 63(241), 319, 320 Hiebl, J., 321, 322, 323(242) Himmel, M. E., 57, 70(267a) Hingerty, B. E., 227, 228(111) Hino, Y.,209, 210, 246 Hinze, W. L., 248 Hirai, H., 209, 210(31) Hirano, D. S., 34 Hirayama, F., 210, 249 Hiromi, K., 234

AUTHOR INDEX Hirst, E. L., 288 Hirter, P., 69 Hitz, W. D., 144, 173(160) Hjerpe, A., 32(92), 33, 37, 55, 56(92), 65(253) Hoagland, P. D., 57 Hodge, J. E., 286, 308, 309, 318, 321 Hogaboom, G. K., 204 HZiland, H., 236 Hokse, H., 44 Honda, S., 30, 31, 32, 33, 34(71), 54(71), 56(80), 66(81), 67, 68(81), 70(78), 71(80), 262, 264(25), 267(25) Hooghwinkel, G. J. M., 45 Hoppe-Seyler, F., 274 Horton, D., 180, 189(6), 197 Horvath-Toro, C., 220, 223(83) Hoshi, H., 232 Hoshino, M., 209 Hoshino, O., 194, 196 Hosur, R. V., 73 Hough, L., 118(130), 119, 120, 121(134), 122(134), 127(134), 157(134) Hounslow, A. M., 239 Howard, D. R., 42 Hrutfiord, B. F., 303 Hudson, C. S., 215 Huebner, A. L., 25, 39(49), 51(49), 64(49) Huekeshoven, J., 319 Hughes, D. E., 33, 65(87) Hughes, S., 65 Hull, S. R., 42, 68 Hullar, T. L., 191 Humphrey, A. E., 300 Humphries, H. P., 282 Hung, C. T., 288 Hunt, B., 90(70), 91(70), 92, 116(70) Hupe, K.-P., 18 Hurd, C. D., 275 Hybl, A,, 218 I

Ido, T., 146(169), 147 Ihara, Y., 249 Ikeda, H., 245 Ikeda, T., 234, 245 Ikehara, M., 181, 182 Ikenaka, T., 57, 256, 268, 270(49) Imai, T., 249 Inch, T. D., 74, 79(5)

343

Innis, D. P., 71 Inoue, M., 67 Inoue, S . , 256, 258(13) Inoue, Y., 219 Irlam, G. A., 62(279), 63 Isbell, H. S., 275, 281(23), 301(23) Isenhour, L. L., 275 Ishizu, A,, 281, 292(43), 293 Ito, Y., 70 Ittah, Y., 86(51), 89, 93(51) Iverson, J. L., 51 Iwata, S., 38 Iyengar, J. R., 265 J

Jacobi, R., 213 Jacobsen, S., 101(94), 102(94), 103, 106(94), 109(94) Jacobson, K., 204 Jacopian, V., 299 Jakoby, W. B., 204 JakovljeviC, J. B., 38, 39(137) James, H., 19, 21, 23(9), 24, 32(39), 33(39), 41(39), 59(39), 60(39), 64(39) James, P., 27 Jansen, H., 67 Janson, J., 301 Jantzen, E., 258, 259(17) Javier-Son, A. C., 274 Jaworska-Sobiesiak, A., 119(133), 120, l23( l33), l24( l33), 12%l33), 127(133), l70( l33), l71( 133) Jeanloz, R. W., 19, 44(19), 59(19), 62(19) Jeffrey, J. E., 263, 264(30) Jen, J. J., 265 Jenkins, I. D., 144(164), 145, 174(164) Jensen, S. R., 101(94), 102(94), 103, 106(94), 109(94) Jentoft, N., 56, 68(261), 256, 257(11), 258(1 I ) Jeon, I. J., 51, 63(238) Jewell, J. S., 197 Jitsuhiro, T., 182 Johansson, I., 299 Johansson, M. H., 303 John, M., 39, 54(151) Johncock, S. I. M., 51 Johnson, D. C., 19, 65 Johnson, L., 19, 20(12), 32(12), 68(12) Johnson, R. N., 75, 76, 80, 86(12), 87(58),

344

AUTHOR INDEX

89, 90(12), 91(12), 93(12), 94(12), 97, 105(11), 146(18), 147(18), 148(11, 12). 149(84), 155(11) Jolly, D., 85(47), 86(47), 87(47), 88(47), 89 Jones, A. D., 21, 23(26) Jones, J. K. N., 25 Jones, M., 56, 68(263), 267 Jones, T. M., 264 Jordaan, A., 138(156), 139(156), 140, 141(156), 142(156) Jurasek, L., 263, 264(32) Jurch, G. R., 314 Jurgens, A., 194

K Kabat, E. A., 43 Kagita, A., 226 Kahle, V., 38, 71(135) Kainuma, K., 38 Kajtar, M., 220, 223(83) Kallury, M. R., 300 Kannan, R., 266 Kano, K., 209 Kaplan, J. N., 204 Karim, K. A., 36 Kasatani, K., 244 Kato, A., 70, 71 Kato, H., 294, 313, 314, 321 Kato, S., 230, 234(120) Katzen, H. M., 297 Katzenbeisser, U., 116, 152(125), 158(125), l70( 129, l75( 125). 177(125) Kaufmann, R. J., 158, 177(182) Kauzmann, W., 227 Kavai, I., 151, 156 Keeling, P. L., 27 Kenner, J., 282 Kent, P. W., 86(54), 89, 92, 95(53), 99(53), 104(53), 105, 112(53), 131, 133, 146(53), 151(176), 152, 155(53), 156(53) Kersten, E., 315 Keyanpour-Rad, M., 159 Khorlin, A. Ya., 121(136), 122 Khripach, N. B., 159 Kieboom, A. P. G., 292 KingMorris, M. J., 293 Kingsbury, W. D., 28 Kirby, G. W., 200

Kirby, J., 203 Kirkland, J. J., 18 Kishi, T., 180, 191(7) Kiss, J., 116, 172(126) Kitagawa, M., 232 Kiyosuke, Y.,233, 244(130) Klein, A., 46 Klein, R. S., 110(111), 111 Klemm, G. H., 158, 177(182) Knapp, D. W., 214 Knoche, W., 230, 234(121) Knudsen, P. J . , 48, 55(212), 57(212) Kobayashi, N., 209, 210(25) Koch, R., 211 Kock, H., 323 Kodali, D., 209 Kodama, C., 68 Koehler, P. E., 315, 316 Koholic, D. J., 191 Koizumi, K., 44,45(191a), 57(189), 247(370b), 248 Kojin, R., 245 KSllnerov6, Z., 87(62), 89 Komiyama, M., 206, 221(92), 222 Konami, Y., 46 Konigstein, J., 279 Konishi, T., 31, 67 Koole, J. L., 208 Koops, J., 64 Koppen, P. L., 33,42,43(170), 45,46, 65(170, 202) Koppler, H., 315, 319(213) Kortlandt, F., 274 Korytnyk, W., 95(85), 97, 113, 120, 121(85), 122(85), 133, 146(147), 147(147), 153(147), 177 Kosakai, M., 55, 68(256) KovBE, P., 77, 92, 161(26), 162(186), 163, 164(26) Kracht, W. R., 20, 53(19) Kranich, W. L., 274 Kranse, F., 323 Krawczyk, S. H., 28 Krishna, R., 300 Kronig, U,, 322 Krzeminski, 2. S., 284 Kuan, F.-H., 219 Kucherov, V. F., 201 Kudo, K., 293 Kuge, T., 217, 221(95), 222

AUTHOR INDEX Kumanotani, J., 21, 33, 56, 57(262), 59(25), 62(25), 70 Kumar, N., 28, 69(57e) Kuo, J. C., 66 Kurata, T., 289, 313 Kurosu, Y.,33 Kuster, B. F., 23, 29, 50(29), 66(29), 67(29) Kyrczka, B., 190

L Laakso, E. I., 35 Laamanen, L., 302 Lacey, M. J., 259 Lach, J. L., 208, 219(13) Ladisch, M. R., 21, 25, 39, 53(22), 54(22) Lafosse, M., 66 Laine, R. A., 42 Lake, B. G., 35 Lambert, J. B., 79 Lamblin, G., 42, 43(171), 46, 59(199), 61 Lammers, J. N. J. J., 208 Lamperstorfer, C., 193 Lamport, D. T. A., 56 Landsman, S. D., 294, 304(105) Lang, P., 192 Larsson, P.-O., 72 Lau, J. M., 20, 57(18) Laude, D. A., 69 Lauer, M., 244 Laufer, D. A., 239 Lautsch, W., 218, 219(79) Laver, M. L., 263, 264(29) Lawrence, J. F., 265 Ledger, P. W., 42, 46(176) Ledl, F., 322 LeDonne, N. C., Jr., 57, 69(270) Lee, C. M., 307 Lee, G. J.-L., 37, 55 Lee, R. E., Jr., 19, 21, 23(9), 24, 32(39), 33(39), 41(39), 59(39), 60(39), 64(39) Lee, R. W.-K. 69 Legendre, M. G., 183 Leger, M., 37, 55(133) Lehnhardt, W. F., 268 Leo, A., 227 Leonard, J. L., 31 Leroy, Y.,46, 62(198) Lester, H. A., 204 Levine, M. L., 217, 220

345

Levy, M., 198 Levy, S., 87(60), 89 Lewis, E. A., 221(89), 222, 223(89) Lim, P. C., 25, 26(48), 33(48), 34(48), 35(48) Lincoln, S. F., 209(37, 38, 39), 210, 234, 239, 242(37, 381, 244(37, 38, 39), 245(140) Lindberg, B., 144(163), 145, 174(163), 251, 269, 281, 291, 292(43), 293, 299, 300, 301, 323, 325 Lindgren, G., 277, 289 Lindner, K., 229, 231(116) Liniere. F., 29 Lipari, J. M., 220, 232(85) Little, M. R., 57, 66(265) Liu, D.-W., 55 Liu, H.-W., 57, 68(266) Livni, E., 87(60), 89 Lloyd, K. O., 255, 256(6) Lloyd, W. J., 159 Lochinger, W., 192 Lochmiiller, C. H., 69 Lockhart, G. L., 289 Loeppky, R. N., 320 Loewus, F., 35 Lomax, J. A., 270 Long, D. E., 51 Lonngren, J., 251 Lopes, D. P., 93(80), 94 Lowendahl, L., 302 Luetzow, A. E., 299 Lumry, R., 225 Lundt, I., 131(146), 132 Lutz, w . , 197

M McCleary, B. V., 271 McCloskey, C. M., 300 McCray, J. A., 204 McGinnis, G. D., 28, 260 Machell, G . , 292, 296, 301, 303(152) McIntire, R. L., 214 McLaughlin, H., 40, 41(154) Maclennan, J. M., 229 McNeil, M., 20, 29, 40, 42, 49(63), 57, 58(63) McNicholas, P. A., 68 MacNicol, D. D., 220

346

AUTHOR INDEX

Macrae, R . , 50, 66 Maeda, M., 86(52), 89, 162(63) Majors, R . E., 67, 68(290, 291), 69 Manius, G. J., 21, 30(27) Manners, D. J., 297 Manor, P. C., 228, 229(114), 239(114) Manville, J. F., 75, 76, 79, 82(14, 15). 83(14, IS), 85, 101(14), 102(14), 103, 129(15, 34), 130(14, 15, 34), 131, 135(34), 136(34), 137(34) Maradufu, A., 94, 163(188), 165 Marce, P., 315 March, J. F., 260, 263(20), 264(20) Marcus, D. M., 85(45), 89, 94, 146(45), 147(45) Marcy, A. D., 52, 53(243) Margeot, J., 204 Markham, A. F., 182 Marks, C., 34 Marlett, J. A., 52, 53(242), 263, 264(33) Marsaioli, A. J., 119(132), 120, 123(132), l24( l32), 1 2 3132). 127(132), l70( 132), 171(132) Martens, J., 317 Martic, P. A., 243 Martin, J. C., 134, 135 Mason, M. E., 315 Matheson, N. K., 271 Mathews, R. A., 267 M a t h , S. A., 21, 61(28) Matolova, M., 306 Matsugi, J., 182 Matsui, Y., 222, 223(98), 226, 233(98) Mauro, D., 36 Mauron, J., 307 Mawhinney, T. P., 255 May, J. A,, Jr., 150(173), I51 Meeley, M. P., 230, 245(122) Mega, T., 256 Mehring, M., 74 Mellier, D., 194 Mellis, S. J., 42, 45, 46(168), 48(193), 60(168) Merkel, K. E., I9 Merrifield, R. B., 199 Meyer-Delius, M., 213, 215(58) Mikes, O., 40 Mikolajczyk, M., 248 Miller, D. L., 203 Miller, R . , 274

Miller, R. E., 286 Miller, R. K., 304, 314 Milligan, L. P., 53, 54(246), 65(246) Mills, F. D., 321 Mithel, B. B., 299 Miyaji, T., 223 Miyake, T., 182 Miyawaki, M., 256, 258(13) Mizowaki, N., 247(370b), 248 Mizushima, M., 294 Mochida, K., 222, 223(98), 226, 233(98) Molton, P. M., 273, 277, 283(37), 284(37), 294, 300(37), 304 Mononen, I., 258 Moody, W., 62(280), 63 Moore, W. E., 263, 275, 276(20) Mopper, K., 19, 20(12), 32(12), 33, 67, 68( 12) Moret, G., 141 Morgan, S. L., 266 Moriwaki, F., 246 Moriyasu, M., 70, 71 Mort, A. J., 56 Moschel, R. C., 28 Moss, C. W., 267 Moye, C. J., 284 Mukaiyama, T., 107(105), 108(105), 109 Mulholland, G. K., 86(56), 87(56), 89 Munsinghe, V. R. N., 188, 189(38, 39) Murai, K., 246 Murata, K., 37, 55(128, 129) Murray, C. T . , 239

N Naim, M., 198 Nakajima, A,, 219 Nakakuki, T., 38 Nakamura, C. Y.,196 Nakanishi, E., 249 Nakano, T., 200 Nakatani, H., 234 Nakayama, T., 314, 321(211) Namiki, M., 309 Nam Shin, J. E., 163(188),, 165 Narasimhan, S., 42, 57(167), 60(167) Narui, T., 38 Natowicz, M., 42, 46 Nebinger, P., 48, 57(214) Neeser, J.-R., 256, 262, 263(27), 270(8)

AUTHOR INDEX Nef, J. U.,301 Nelson, D. A,, 277, 283(37), 284(37), 290, 294, 300(37), 304, 316 Nelson, E. C., 286 Neukom, K., 290 Nevins, D. J., 262 Newth, F. H., 284 Ng Ying Kin, N. M. K., 44, 45(186), 46(186), 48(186), 64(186) Ni, X.-R., 210 Nichols, S. B., 275 Niedermeier, W., 260, 266 Niesner, R., 39, 300 Nikolov, Z. L., 23, 32(90), 33, 38, 39(137), 41 Nishimoto, S. K., 42, 46(176) Nodzu, R., 293 Noel, D., 23, 39, 67(34) Noltemeyer, M., 228, 229(114), 239(114) Nomura, H., 230, 234(120) Norbonne, J. M., 204 Nordin, P., 67 Nothnagel, E. A,, 40 Nursten, H. E., 307, 322 Nyhammar, T., 311, 312 0 Oades, J. M., 263 Odell, G. V., 316 Ogata, S., 255, 256(6) Ogawa, T., 87(64), 89, 161(64), 207, 209 Ohashi, M., 244 Ohlson, S., 31, 72 Ohtsuka, E., 181, 182 Ojha-Poncet, J., 141 Okada, Y., 44, 57(189, 190) Okubo, T., 209, 235 Olesker, A., 87(61), 88(61), 89 Olieman, C., 24, 51(38), 52, 64 Olsen, I., 258 Olson, W. K., 104(100), 105 Olsson, E., 291 Olsson, K., 311, 312, 313, 314 O’Meara, D., 282 Onda, M., 218 Oparaeche, N. N., 188, 189(38, 39) Oppenauer, R., 276, 288(27) O’Reilly, R., 322 Orstan, A., 226, 234, 238(137)

347

Osa, J . , 209, 210, 246, 247(169) Oshima, R., 21, 33, 56, 57, 59(25), 62(25), 70 Osman, S. F., 57, 69(269) Ossowski, P., 41 Otagiri, M., 223, 249 Otani, S., 293 Ototani, N., 68 Overend, W. G., 301

P PacBk, J., 87(62), 89, 144, 145, 152, 173(161) Pachla, L. A , , 35 Paice, M. G., 263, 264(32) Painter, T. J., 324 Palasinski, M., 274 Pallasch, G., 55 Palmer, J. K., 51, 54, 64(233) Parente, J. P., 43, 46, 51, 60(179), 62(198), 63(229) Parrish, F. W., 51, 63(241) Partlow, E. V., 263, 264(30) Patchornik, A., 179, 181, 182, 184, 188(1), 193, 198(58), 202, 203, 204 Pate, B. D., 86(48), 89, 104(48), 142(48), 143(48) Patil, V. J., 123, 124(137), 125(137), l27( 137) Patrick, D. W., 20, 53(19) Paulsen, H., 321 Pav, J. W., 55 Pecina, R., 20, 26, 39(13), 53(13), 54(13) Pedersen, C., 77, 78(28), 84(42), 85, 97(87), 98, 101(94), 102(94), 103, 106(94), 107(107), 108, 109, 131(146), 132, 134, 137, 138, 166(25), 168(107), 169(107) Peer, H. G., 320 Pendergast, D. D., 227 Penglis, A. A. E., 74, 75(10), 76(10), 77(10), 80(10), 118(130), 119, 120, 121(l34), 122(l34), l27( 134), l57( 134) Percival, E. G. V., 288 Perlin, A. S., 94, 163(188), 165 Pernemalm, P.-A., 277, 290, 312, 313, 314 Pettersen, R. C., 33, 52(83), 53(83), 63(83), 64(83), 263 Pettit, B. C., Jr., 51 Phillip, B., 297, 299

348

AUTHOR INDEX

Phillips, G. O., 182 Phillips, L., 75, 77, 78, 79(23, 29), 82(23), 86(23, 24), 87(23, 24), 90(23), 91(23), 93(23), 94(23), 95(23), 160(24), 162(24), 163(24), 164(24) Picq, D., 117(129), 118, 119, 128(129) Pillai, V. N. R., 179 Pincock, J. A., 194 Pirisino, J. F., 23, 25(30), 50(30), 51 Pittet, A. O., 25 Plant, P. J., 198 Plattner, R. D., 191 Pocsik, I., 231 Podolsky, D. K., 45, 46(196) Polacheck, I., 198 Pollock, C. J., 269 Poloskq, J., 292 Polta, J. A., 19 Popoff, T., 276, 279, 280, 282, 289, 290, 294(49), 295(49), 313 Popp-Ginsbach, H., 321 Porsch, B., 19, 24(10), 33(10), 38, 59(10, 143) Porter, W. H., 268 Posner, G. H., 98, 166(89) Post, A,, 261, 267(23) Praznik, W., 39 Preston, J. F., 40, 41(160) Prey, V.,293 Prince, S., 28 Prout, C. K., 129(141), 130(141, 145), 131, 135(141) Pulley, A. O., 206

Q Que, L., Jr., 173

R Rabel, F. M., 38 Radeos, M., 221(96, 97), 222, 225(96) Rajakyla, E., 28, 34 Rajender, S., 225 Rao, G. V., 173 Rao, V. S. R., 206 Rasmussen, J. R., 163, 164(187) Rasmussen, P., 138 Rauh, S., 230, 234(121) Raupp, D. L., 33, 51(85)

Re, A., 95(82), 96, 99(82) Reddy, G. S., 90(65), 92, 93(65), 94(65), 96(65), 100(65), 106(65), 119(65), 120(65), 122(65), 149(65), I50(65), 162(65), 163(65), 164(65), 165(65), 168(65), 17l(65), 175(65) Redmond, J. W., 68 Redmore, D., 284 Rees, D. A., 230 Refn, S., 84(42), 85 Reggiani, M., 233, 245(127) Reichman, U., 110(108), 111, 138(108) Reichstein, T., 276, 288(27) Reilly, P. J., 23, 33, 41 Reinhold, V. N., 56, 57(260), 69, 70 Rendleman, J. A., Jr., 301 RepBSovA, L., 292 Rewicki, D., 315, 319(213) Reynolds, D. L., 35 Reynolds, T. M., 286, 308 Rice, F. A. H., 277 Rice, M. J., 271 Rich, D. H., 199 Richard, S., 204 Richards, G. N., 62(280), 63, 282, 296, 301, 302(151), 303(152, 155). 306 Richardson, A. C., 118(130), 119, 120, 121( I 341, 122(1341, l27(134), l57( 134) Richmond, M. L., 27 Richtzenhein, H., 303 Riddel, F. G., 79 Rideout, D. C., 210 Riehl, T. E., 248 Riley, D. A., 107(105), 108(105), 109 Rinaudo, M., 32, 38, 39, 269 Ripmeester, J. A., 307, 325 Rist, C. E., 309 Ritchie, R. G. S . , 191 Robards, K., 32 Robinson, B. H., 234, 237(142), 238(142), 239(142) Robinson, J., 67 Rocklin, R. D., 30, 65(72) Rodriguez, L. J., 230 Rohrbach, R. P., 230, 234, 236(119) Rojas, R. R., 24, 32(39), 33(39), 41(39), 59(39), 60(39), 64(39) Rolf, D., 271 Romeo, T., 40, 41(160) Root, D. F., 263, 264(29)

AUTHOR INDEX Rosanske, T. W., 239 Rosenbrook, W., 107(105), 108(105), 109 Rosenfelder, G., 56, 68(264), 69(264) Ross, J. B. A., 226 Roth, K., 73 Rubinstein, M., 203 Rundle, R. E., 214, 218 Russell, K. R., 319 Rutar, V., 94, 164(76) Rydholm, S. A., 297

S Sachetto, J.-P., 309 Sadeh, S., 187 Saeman, J. F., 263, 298 Saenger, W., 206, 209, 225, 227, 228, 229, 232(104), 233(104) Sage, U., 321 Saito, R., 209 Sakurai, Y.,289 Salemis, P., 57, 66(267) Salimi, S. L., 35 Samarco, E. C., 51, 63(229) Sammes, P. G., 200 Samuel, J., 116 Samuelson, O., 31, 38, 291, 301, 302, 303 Sand, D. M., 220, 230(86), 240(86) Sandberg, A.-S., 36 Sanger, M. P., 56 Sano, T., 234 Sarel-Imber, M., 144 Sartorelli, A. C., 150(173), 151 Sasaki, M., 234 Sasaki, Y.,209(36), 210 Sato, M., 248 Satoh, J. Y.,196 Satyamurthy, N., 86(55), 87(55), 89, 146(167), 147 Sawada, M., 182 Sawaki, S., 194, 196 Schaaf, E., 215, 217(70) Schaffer, R., 283 Schardinger, F., 211, 212, 215(53), 217(53) Schauer, R., 36, 37(119, 120, 121, 122) Schiller, R. L., 210, 234, 239(139), 242(139), 245(140) Schlabach, T. D., 67 Schlaeger, E. J., 204 Schlenk, H., 220, 230(86), 240(86)

349

Schlenk, W., Jr., 217 Schmidt, J., 39, 54(151) Schmit, A. S., 19, 44(19), 59(19), 62(19) Schofield, P., 198 Schols, H. A., 265 Scholz, N., 36, 37(119) Schroeder, L. R., 300 Schwald, W., 52, 53(245), 298 Schwandt, V. H., 33, 52(83), 53(83), 63(83), 64(83), 263 Schwartz, A., 298 Schwartz, L. M., 221(88, 90,91, 92), 222, 225(90), 239 Schwarzenbach, D., 80, 140(37), 141, 154(178), 155 Schwarzenbach, R., 20, 38 Schweizer, T. F., 262, 263(27), 266(27), 268(27) Schwentner, J., 265 Scobell, H. D., 25, 51, 64(232) Scott, R. W., 275, 276(20) Sebastian, J. F., 223 Seidl, S., 100, 116(91), 166(91), 167(91), 170(91) Seiyama, A., 234, 238(147, 1481, 245( 148) Seki, T., 35 Seldin, D. C., 37, 55(131), 60(131) Selman, S., 291 Selvendran, R. R., 260, 263(20), 264(20) Seng, P. N., 266 Seno, N., 37, 55(131), 60(131) Sephton, H. H., 301 Serebryakov, E. P., 201 Serianni, A. S., 293 Seshadri, R., 28, 69(57e) Severin, T., 321, 322 Seymour, F. R., 191 Shafizadeh, F., 274 Sharma, M., 95(85), 97, 113, 120, 121(85), 122(85), 151, 156, 177 Sharon, N., 254, 256(5), 270(5) Sharp, J. K., 41, 42, 59(165), 60(165) Sharples, A., 298 Shaw, P. E., 51, 65(234), 286, 294, 311, 3 19(59) Sheehan, J. C., 200, 201 Sherblom, A. P.. 46 Sherr, B., 307 Sherrard, E. C., 298

350

AUTHOR INDEX

Shibamoto, T., 317 Shigematsu, H., 313 Shimizu, N., 246 Shimokawa, K., 246 Shoemaker, S. P., 54 Shu, C.-K., 318 Shukla, A. K., 36, 37(119, 120, 121, 122) Shulman, M. L., 121(136), 122 Sidhu, R. S., 158, 177(182) Siegel, B., 208, 226(14) Sihtola, H., 302 Silber, P., 181 Silver, H. K. B., 36 Simkovic, I., 306, 321(174) Sirimanne, P., 19, 29, 32(5), 33, 62(19), 63, 256, 257(12) Sjostrom, E. S., 305 Slavin, J. L., 52, 53(242), 263, 264(33) Slodki, M. E., 39, 60(149), 191 Sloman, K. G., 50 Smale, S. T., 163, 164(187) Smiley, K . L., 39, 60(149) Snyder, L. R., 18 Somawardhana, C. W., 93(77), 94, 96(77), 149(77), 150(77), 151, 165(77), 175(77) Sondey, S. M., 19, 21(8), 22(8), 23(7, 8), 2381, 61(8), 62(8), 71(8) Sonobe, H., 313 Sowden, J. C., 281, 282, 291(42) Speck, J. C., Jr., 281 Spellman, M. W., 20, 57(17) Spiro, M. J., 33 Spotswood, T. M., 239 Squire, A., 33, 34(96), 54(96) Srivastava, H. C., 100 Srivastava, V. K., 100 Stacy, C. I., 296 Stahnke, G., 192 Staines, W., 199 Staros, J. V., 204 Steele, E. M 5 1 Steffen, R., 323 Steiner, P. R., 76, 100. 106(104), 108(104), 109, I15(22), 116(22) Stetten, M. R., 297 Stewart, T. S., 270 Stezowski, J. J., 229 Stikkelman, R. M., 36 Stotz, E. H., 207 Straub, T. S., 223

Strecker, G., 43, 60(179) Street, I. P., 146(170), 147 Stroh, J. G., 70 Stutz, E., 288 Su, T. L., 110(111), 111 Sugii, A., 31 Sugimoto, S., 314, 321(211) Sukumar, S., 74 Sundararajan, P. R., 206 Suortti, T., 326 Suslova, L. M., 201 Suzuki, M., 209(36), 210, 269 Suzuki, S., 30, 31, 33(71), 34(71), 54(71), 56(80), 67, 70(78), 71(78, 80), 262, 264(25), 267(25) Svahn, B. M., 128, 171(140), 172(140) Svensson, S., 251 Swiedler, S. J., 20, 43, 47(16) Symanski, E. V., 33, 61(89), 62(89) Syngg, B. E., 326 Szarek, W. A,, 191 Szejtli, J., 206, 208(6), 209, 220, 223(83)

T Tabushi, I., 206, 233, 235, 244(130), 246 Tafuri, S. T., 163, 164(187) Taguchi, K., 234 Takahashi, K., 209, 210 Takahashi, M., 33, 67(87) Takahashi, T., 196, 296 Takahashi, Y., 87(64), 89, 125(138), 126, 132(138), 135(138), 161(64), 207 Takai, N., 70 Takazano, I., 48, 55(217) Takemoto, H., 68, 268, 270(49) Takenoshita, I., 209 Takeo, K., 217, 221(95), 222 Takeuchi, T., 70 Tamaki, T., 210 Tnnnkn, J , , 325 l'anaka, M., 27 Tanuka. S . , 181. 182 lanaka, T., 181, 182 Tanaka, Y., 48, 55(217) TBnBsescu, I., 188 Tang, P. W., 20, 56(15), 57. 68(15, 272) T a m , C. H., 110(110), 111, 138(110) Tanret, G., 182 Tashima, S., 191

35 I

AUTHOR INDEX Tatum, J . H . , 286, 294, 314, 319(59) Taylor, A. F., 67 Taylor, C., 41 Taylor, N. F., 86(53), 89, 90(53), 92, 93(80), 94, 95(53), 99(53), 104(53), 105(53), l10(109), 1 I I, 112(53), 116, 146(53), 155(53), 156(53) Teng, G., 29 Tesarik, K., 38, 71(135) Tewson, T. J., 99 Thakkar, A. L., 218 Thawait, S ., 62(278), 63 Theander, O., 276, 277, 279, 280, 28 1, 282, 289, 290, 291, 292(43), 293(43), 297, 299, 300, 305(118), 306, 313, 316, 323, 324, 325, 326 Thibault, J.-F., 40 Thiem, J., 265 Thomas, S. R., 86(59), 87(59), 89 Thompson, A., 262, 263(26a), 270 Thoraval, D., 195, 196(65) Tieckelmann, H., 37, 55 Tilden, E . B., 215 Timbie, D. J., 51 Timmell, R. E., 305 Timpa, J. D., 183 Tipson, R. S., 269 Tjioe, T. T., 36 Tjoeng, F.-S., 199 Tokola, R. A,, 35 Tolman, R. L., 104(98), 105, 143(98), 155(98) Tomana, M., 266 Tomasik, P., 274 Tomita, Y.,31, 246 Tong, E. K., 199 Torello, L. A., 260, 267(22) Toshima, N., 209, 210(31) Trainor, G. L., 84(44), 85, 95(44), 96(44), 99(44) Tressl, R., 315 Tronchet, J . M. J., 80, 112, 140(37), 141, 154(178), 155, 169(114) Tropsch, H., 299 Trugo, L. C., 66 Tsao, C. S., 29, 35, 36(66) Tsao, G. T., 21, 25, 34, 39, 53(22), 54(22) Tscherne, R. J . , 21, 30(27) Tsuchiya, T., 125(138), 126, 132(138), 135(138), 180, 191(7)

Tsuji, T., 46 Tsunehisa, S., 46 Tung, C. H., 209 Turco, S. J., 43, 68 Turro, N . J., 209, 235 U

Uekama, K., 210, 249 Ueno, A., 209, 210, 246, 247(169) Uenoyama, S., 209, 210(31) Ukena, J., 203 Umazawa, K., 201 Umezawa, B., 194, 196 Umezawa, S., 180, 191(7) Utamura, T., 247(170b), 248

V Valent, B., 42, 59(165), 60(165) Valentekovic-Horwath, S., 132(147), 133, 146(147), 147(147), 153(147) van Bekkum, H., 292 Van Damme, F., 31 van den Berg, G. R., 248 van den Berg, J. H. M., 68 van den Eijnden, D. H., 33, 42, 43(88, 170), 45, 46, 65(170, 202) Van den Ouweland, G. A. M., 320 Van Der Aalst, M. J. M., 51 van Eikeren, P., 40, 41(154) van Etten, R. L., 223, 244 van Halbeek, H., 42, 43, 46(172), 79 van Hooidonk, C., 222, 227, 248 van Riel, J. A. M., 52 Van Rijn, C. J. S., 85, 86(39), 87(39), I13(39) Varki, A., 36 Varma, R., 265 Varma, R. S., 265 Varvoglis, A. G., 203 Vasella, A., 98, 166(89a) Vegh, L., 191 Veregin, R. P., 219 Verhaar, L. A. T., 23, 29, 34, 50(29), 51, 66(29), 67(29) Vernengo, M. J., 13 Vernin, G., 307 Verzele, M., 21, 31, 58, 61(24) Vestal, M. L., 69

352

AUTHOR INDEX

Villani, R. P., 234, 245(140) Villiers, A., 211 Vliegenthart, J. F. G., 79 Voragen, A. G. J., 29, 33(67), 34(67), 40(67), 41, 54(67), 265 Voyksner, R. D., 69 Voznyi, Y. V., 132(150), 133 Vrfitnq, P., 30, 39(69), 40, 67, 68 Vuorinen, T., 292 W

WagstafTe, P. J., 51 Wakabayashi, T., 181, 182 Waldmann, E., 293 Walker, G. W., 41 Walker, M. E., 194 Wall, R. A., 25 Walters, D. G., 35 Walther, H. J. 69 Wan, C. N., 146(169), 147 Wang, W. T., 57, 69(270) Ward, T. J., 233, 248 Warren, C. D., 19, 44(19), 59(19), 62(19) Warthesen, J. J., 38, 51(145) Watanabe, K. A., 110(108), 111, 138(108) Watanabe, N., 67 Waterman, H. I., 274 Webster, G. H., 299 Wegener, G., 298 Weingarten, G. G., 200 Weiss, A. H., 274 Welch, J. T., 104(101), 105, 128, 171(140), 172(140) Welch, M. J., 99 Wennerblom, A., 302 Wentz, F. E., 52, 53(243) Westerlund, E., 279, 283 Westphal, G., 317 Westwood, J. H., 75, 76, 83(41), 84(41), 85, 86(12), 90(12), 91(12), 92, 93(12), 94, 95(12), 97, 99(67), 105(1I), 114(72), 148(11, 12), 149(84), 151. 155(11) Wetzel, D., 36 Wheals, B. B., 23 Wheaton, R. M., 24 Whistler, R. L., 292, 297, 301, 305, 306 White, A. R., 54 White, C. A., 38 White. P. C.. 23

Whitelaw, M., 32 Whitt, F. R., 296 Wiebe, L., 97(87), 98 Wieland, T., 192, 193 Wieruszeski, J.-M., 43, 45 Wilcheck, M., 204 Williams, D. M., 180, 189(6) Williams, J. M., 20, 56( 1 3 , 57, 68(15) Wills, R. B. H., 65 Wilson, C. W., 51 Wilson, D. C., 326 Wilson, R. M., 200 Wimalasiri, P., 65 Wing, R. E., 182 Winsauer, K., 65 Winzler, R. J., 268 Withers, S. G., 146(170), 147 Wnukowski, M., 51, 67(235) Woelk, H. U., 323 Wojcik, J. F., 226 Wolf, D. D., 269 Wolfe, L. S., 44,45(186), 46(186), 48(186), 64(186) Wolfrom, M. L., 262, 263(26a), 270, 295, 296 Wong, C. H., 90(66), 91(66), 92, 99(66), 109(66), 1 lO(66) Wong, T. C., 94, 164(76) Wood, K. R., 151(176), 152 Wood, R., 25, 30(46) Woodward, R. B., 193, 198(58) Woollard, D. C., 27, 51(57) Wray, V., 75, 77, 78, 79(23), 81, 82(23), 8 W 3 , 241, 87(23, 241, 90(23), 91(23), 93(23), 94(23), 95(23), 160(24), 162(24), 163(24), 164(24) Wright, J. A., 110(109), 111 Wu, A. M., 43 Wyss, P. C., 116, 172(126)

Y Yagi, Y., 248 Yamada, T., 182 Yamaguchi, Y., 35 Yamamoto, M., 234 Yamamoto, Y., 218 Yamazaki, N., 293 Yang, M. T., 53, 54(246), 65(246) Yates, A. J., 260, 267(22) Yeransian, J. A., 50

AUTHOR INDEX Yeung, E. S., 66 Yokokawa, C . , 304 Yokoyama, M. T., 264 Yokoyama, Y., 37, 55(128, 129) Yoruzu, T., 209 Yoshida, K., 293 Yoshida, N., 234 Yosizawa, Z., 55 Young, M . , 29, 36(66)

353 Z

Zaikov, G . E., 251 Zehavi, U . , 179, 180, 181, 182, 184, 187, 188, 193, 198 Zen, S., 191 Zent, J. B . , 307 Zhen, Z., 209 Zygmunt, L. C., 51, 63(228)

SUBJECT INDEX A Acetaldehyde, 321 Acetals, protection as, 182-189 Acetic acid cyclodextrin inclusion complexes with, 22 1 liquid chromatography, 53-54 pH of aqueous solutions of, 252 Acetoin formation, 294 from hydrothermolyzed cellulose, 304305 Acetol formation, 293 high-temperature transformation, in alkali conditions, 284 Acetolysis, for cleavage of glycosidic linkages, 269-270 Acetonitrile, cyclodextrin inclusion complexes with, 221 N-Acetyl-9-deoxy-9-fluoroneuraminic acid, I3C-n.m.r. data for, 177 2-Acetyl- 1-ethylpyrrole, formation of, 3 133 14 N-Acet ylglucosamine glycosidic, in glycoproteins, 257 linked to L-asparagine, N-glycosylic linkage, 255 2-Acetyl-3-hydroxyfuran, 320-32 1 2-Acetylpyrrole, formation of, 312313 1-O-Acetyl-2,3,5-tri-O-benzoyl-4-deoxy-4fluoropentofuranose -, a-L-lyxo-, IH-and I9F-n.m.r. data for, 143 -, p - D - r i b , 'H- and "F-n.m.r. data for, 143 a-Acid glycoprotein, oligosaccharides, liquid chromatography separation, 4243 Acid glycosaminoglycans, quantitation of uronic acids in, 258 Acylpyrrole formation, from 3-deoxyhexos-2-ulose, by Strecker degradation, 311-312 Adamantenecarboxylate ion, cyclodextrin inclusion complexes with, 221

Adamantenecarboxylic acid, cyclodextrin inclusion complexes with, 221 Adriamycin analogs, 28 Aldaric acids, analytical high-performance liquid chromatography, 33-35 Aldehydes, protection of, 195-198 Alditols, liquid chromatography, 33 pre-column derivatization procedures, 68 Aldonic acid acid decomposition, 252 analytical high-performance liquid chromatography, 33-34 ultraviolet-absorbances of, 65 Aldopentoses acid decomposition, 252 high-temperature transformation, 275284 Aldose isomerization of, to ketose, with hydride shift, 287 liquid chromatography methods for analysis of, 33 transformations, basic conditions, 28 1 Aldotetroses, high-temperature transformation, 275-284 Aldotrioses, high-temperature transformation, 275-284 Aldulosonic acids, analytical high-performance liquid chromatography, 34 Alduronic acid decarboxylation, 306 high-temperature transformation acidic conditions, 284-291 basic conditions, 291-295 Alginic acid, 307 oligomers, liquid chromatography, 40 D- Allop yranoside -, methyl 6-azido-3,6-dideoxy-3-fluoro-

P-

"C-n.m.r. data for, 171 'H- and I9F-n.m.r. data for, 119 -, methyl 3-deoxy-3-fluorop anorner, IH-and IgF-n.m.r. data for, 90 -, 4,6-O-isopropylidene-p-, 'H- and IyF-n.m.r. data for, 90 -, 6-O-pivaloyl-p-, 'H- and I9F-n.m.r. data for, 90 354

SUBJECT INDEX

355

-, 6-O-trityl-P-, 'H- and I9F-n.m.r. -, 4,6-O-benzylidene-2,3-dideoxy-2fluoro-adata for, 90 -, methyl 3-deoxy-3-fluoro-P-, benzyl 3-azido-, 'H- and 19F-n.m.r. data for, 117 13C-n.m.r.data for, 162 -, 6-O-pivaloyl-P-, T - n . m . r . data -, benzyl 3-benzamido-, 118 -, methyl 3-amino-, 'H- and I9Ffor, 162 Allopyranosyl fluoride n.m.r. data for, 117 -, D-, 3-azido-4,6-O-benzylidene-3-, methyl 3-benzamido-2,3-dideoxy-2deoxy-Pfluoro-aW-n.m.r. data for, 170 -, 4,6-O-benzylidene-, IH- and I9F'H- and 19F-n.m.r. data for, 117 n.m.r. data for, I18 -, 2,3,4,6-tetra-O-acetyl-~-, IH- and -, 4,6-di-O-acetyl-, 'Hand I9F19F-n.m.r. data for, 82 n.m.r. data for, 118 Allose, liquid chromatography methods for -, 4,6-di-O-benzoyl-, 'H- and I9Fanalysis of, 33 n.m.r. data for, 118 Alpha-I-acid glycoprotein, hydrolysis, with -, methyl 4-O-benzoyl-6-bromo-2,3,6trifluoroacetic acid, 268 trideoxy-2-fluoro-aAlternative chair conformation, 7 -, 3-benzamido-, 'H- and 19F-n.m.r. D-Altropyranoside data for, 123 -, 3-amino-2,3-dideoxy-2-fluoro-a-, -, 3-(trifluoroacetamido)-, 'H- and derivatives I9F-n.rn.r. data for, 123 'H- and I9F-n.rn.r.data for, 117-1 18 -, methyl 4,6-O-benzylidene-2,3-diN-containing, synthetic precursors, deoxy-2-fluoro-a'H- and I9F-n.m.r. data for, 117-, 3-(diallylamino)-, 'H- and I9FI I8 n.m.r. data for, 118 -, 3-amino-2,3,6-trideoxy-2-fluoro-6-, 3-(trifluoroacetamido)-, 'H- and halogeno-a-, derivatives '9F-n.m.r. data for, 118 IH- and I9F-n.m.r. data for, 123 -, methyl 2,3,6-trideoxy-2-fluoro-aN-containing synthetic precursors, 'H-, 3-(trifluoroacetamido)and '9F-n.m.r. data for, 123 I3C-n.m.r. data for, 170 -, benzyl 3-benzamido-2,3,6-trideoxy-2IH- and I9F-n.m.r. data for, 124 fluoro-a-, 'H- and 19F-n.m.r. data -, 3-aminofor, 123 I3C-n.m.r. data for, 170 -, benzyl 2,3-dideoxy-2-fluoro-aIH- and I9F-n.m.r. data for, 123 -, 3-azido-6-O-(methylsulfonyl)-, IH-, 3-benzamido-4-0-benzoyland I9F-n.m.r. data for, 118 13C-n.m.r. data for, 171 -, 3-benzamido-, IH- and I9F-n.m.r. 'Hand 19F-n.m.r. data for, data for, 118 124 -, 3-benzamido-6-O-mesyI-, 'H- and -, 3-benzamido-4-O-benzoyl-6I9F-n.m.r. data for, 118 bromo-, I3C-n.m.r. data for, 170 -, 3-benzamido-6-O-tosyI-, 'H- and I9F-n.m.r. data for, 118 D-Altropyranosyl fluoride, 2,3,4,6-tetra-O-, benzyl 2-fluoro-a-, 3-benzamidoacetyl2,3,6-trideoxy-, I3C-n.m.r.data for, a anomer, 13C-n.m.r.data for, 160 170 p anomer, V-n.m.r. data for, 160 -, benzyl 2-fluoro-2,3,6-trideoxy-6-iodo-Altrose, liquid chromatography methods afor analysis of, 33 -, 3-azido-, 'H- and 19F-n.m.r. data Amadori compounds for, 123 2,3-enolization in weak acids, 320 -, 3-benzamido-, 'H- and 19F-n.m.r. formation of, 307-308 data for, 123 Amadori rearrangement, 3 11

356

SUBJECT INDEX

formation of 3-deoxyhexo-2-dose by way of, 311 mechanism of, 308-309 Amides, protection as, 194 4-(Amidosulfonylmethyl)-6-methoxy-2-(4methylphenyl)quinoline, photodecomposition of, 194 Amines, catalytic effect, on formation of products from Maillard reaction, 318321 Amino acids, catalytic effect, on formation of products from Maillard reaction, 318-321 2-Aminobenzoic acid, cyclodextrin inclusion complexes with, 222-224 4-Aminobenzoic acid, cyclodextrin inclusion complexes with, 222-224 . p-Aminobenzoic hydrazide, for enhancing detectability of carbohydrates, 67 Amino compounds, carbohydrate transformation in presence of, 307-323 Amino-containing sugars, Onodera's work on, 3 Aminodeoxyhexofuranoses, fluorinated, IH-and I9F-n.m.r. data for, 127128 Aminodeoxyhexofuranosides, fluorinated, IH-and 19F-n.m.r. data for, 127-128 Aminodeoxyhexopyranosyl fluorides 'H- and 19F-n.m.r. data for, 117 N-containing, synthetic precursors, IHand 19F-n.m.r. data for, 117 Aminodeoxypentopymosides, fluorinated, IH-and 19F-n.m.r. data for, 128 Aminodideoxy-3(or 4)-flUOrO sugars IH- and I9F-n.m.r. data for, 118 N-containing synthetic precursors, IHand 19F-n.m.r. data for, 119 Aminodideox y-6-fluoro sugars, IH-and 19F-n.m.r. data for, 120-122 Amino sugars amino groups of, protection of, 192194 difluorinated, 'H- and 19F-n.m.r.data for, 157 fluorinated, W-n.m.r. data for, 170 fluorinated unsaturated, 'H-and I9Fn.m.r. data for, 126-127 N-containing, synthetic precursors, I T n.m.r. data for, 170

Amino-2,3,6-trideoxy-2-fluorohexopyranoses, IH-and 19F-n.m.r.data for, 125-126 3-Amino-2,3,6-trideoxy-2-fluoro-hexopyranoside derivatives 'H-and I9F-n.m.r. data for, 123-125 N-containing synthetic precursors, IHand I9F-n.m.r. data for, 123-125 Amino-2,3,6-trideoxy-2-fluorohexopyranosides, IH- and 19F-n.m.r. data for, 125-126 Amino-2,3,6-trideoxy-2-fluorohexopyranosyl halides, 'H-and I9F-n.m.r. data for, 125-126 Amobarbital, cyclodextrin inclusion complexes with, 223, 224 Amylopectin, 295 high-temperature transformation of, 296297 Amylose, 295 alkaline hydrothermolysis of, 296 Anabaena flosaquue, extracellular polysaccharide, hydrolysis of, 253, 260 Anhydro-4-O-benzyl-3-deoxy-3-fluoro-~Daltropyranose, 2-O-acetyl-l,6-, 'H- and I9F-n.m.r. data for, 114 2,5-Anhydro-l-deoxy-l, 1-difluoro-Dhexitol -, arubino-, IH-and 19F-n.m.r.data for, 151 -, ribo-, IH-and 19F-n.m.r. data for, 152 -, 3,4,6-tri-O-acetyl-, IH- and I9Fn.m.r. data for, 152 1,5-Anhydro-6-deoxy-6-fluoro-~-uru binohex-1-enitol -, 3,4-di-O-acetyl-l ,Zdideoxy-, 'H- and I9F-n.m.r. data for, 113 -, 4-O-benzyl-3-deoxy-, IH-and I9Fn.m.r. data for, 113 -, 3,4-di-O-benzyl-, IH- and I9F-n.m.r. data for, 113 Anhydro-3-deoxy-3-fluoro-P-~-idopyranose, 2,4-di-O-acetyl-l,6-, IH-and 19F-n.m.r. data for, 114 1,6-Anhydr0-2,4-dideoxy-2-fluoro-P-~erythro-hexopyranos-3-ulose,'H-and 19F-n.m.r. data for, 114 Anhydroglucose, liquid chromatography, 53-54

SUBJECT INDEX

357

Anhydrohexofuranose derivatives, diArabinopyranose fluorinated, 'H- and I9F-n.m.r. data -, D-,1,3,4-tri-O-acetyl-2-deoxy-2for, 151-152 fluoro-pAnhydrohexopyranose derivatives, diW-n.m.r. data for, 167 fluorinated, IH-and I9F-n.m.r. data IH-and 19F-n.m.r.data for, 104 for, 151-152 -, 3-deoxy-3-fluoro-p-, IH-and I9F1,5-Anhydrohexopyranose derivatives, n.m.r. data for, 105 fluorinated, IH-and 19F-n.m.r. data D- Arabinopyranoside -, methyl 4-0-allyl-2-amino-2,3-difor, 113 I ,6-Anhydrohexopyranose derivatives, deoxy-3-fluoro-p-, IH-and I9Ffluorinated, IH- and 19F-n.m.r. data n.m.r. data for, 128 for, 114 -, trifluoromethyl 3,4-di-O-acetyl-P-, 3,dAnhydrohexose derivatives, fluoriIH-and I9F-n.m.r. data for, 104 nated, IH-and I9F-n.m.r. data for, L-Arabinopyranoside, methyl 4-deoxy-4I I5 fluoroAnilinium perchlorate, cyclodextrin inclua anomer sion complexes with, 222, 224 Wn .m .r. data for, 168 'H- and 19F-n.m.r. data for, 106 Anno, K., 9 P anomer 2-Anthracenesulfonate, inclusion complex 13C-n.m.r.data for, 168 with gamma cyclodextrin, 210 IH- and I9F-n.m.r. data for, 106 D-Apiose, 14 Arabinitol, liquid chromatography methods D-Arabinopyranosyl fluoride -, 3,4-O-acetoxonium-2-O-methyl-, IHfor analysis of, 33 and 19F-n.m.r.data for, 101 o-Arabinofuranoside IH-, 1,2-di-O-acetyl-5-O-benzoyl-2-deoxy- -, 3,4-O-benzoxonium-2-O-methyl-, and I9F-n.m.r. data for, 101 2-fluoro-3-0-formyl-, 3(or 4)-O-benzoyl-2-O-methyl-p-,'Ha anomer, IH- and 19F-n.m.r. data for, and 19F-n.m.r.data for, 102 141 -, 2-deoxyp anomer, IH- and I9F-n.m.r. data for, -, 2-bromo-p-, 'H-and 19F-n.m.r. 142 data for, 135 -, methyl 2,5-di-O-benzoyl-3-deoxy-3-, 3,4-di-O-acetyl-2-bromo-a-, 'Hfluoro-a-, IH- and I9F-n.m.r. data and 19F-n.m.r. data for, 135 for, 112 -, 3,4-di-O-acetyl-2-iodo-a-,IH-and -, methyl 2-deoxy-2-fluoro-a19F-n.m.r. data for, 135 -, 5-O-benzyl-, IH-and I9F-n.m.r. -, 3,4-di-O-acetyl-2-deoxy-2-fluoro-~-, data for, 11 1 IH-and I9F-n.m.r. data for, 155 -, 3,5-di-O-benzyl-, IH-and I9Fn.m.r. data for, 111 -, 3,4-di-O-acetyl-2-O-methyl-p-, 'HIH-and I9F-n.m.r. data for, 11 1 and I9F-n.m.r. data for, 101 Arabinofuranosyl fluoride -, 3,4-di-O-benzoyl-2-O-methyl-, IHand I9F-n.m.r. data for, 101-102 -, 3,5-di-O-benzoyl-2-0-methyl-, I3C-, 2,3,4-tri-O-acetyl-, IH- and I9Fand I9F-n.m.r. data for, 106 -, 2,3,5-tri-O-benzoyl-a-~-,n.m.r. data n.m.r. data for, 101 for, 106, 168 -, 2,3,4-tri-O-acetyl-P-, W-n.m.r. data for, 161 -, 2,3,5-tri-O-benzyl-, 'H- and I9Fn.m.r. data for, 107 -, 2,3,4-tri-O-benzoyl-a-, 'H- and I9F-, 2,3,5-tri-O-benzyl-a-~-, T-n.m.r. n.m.r. data for, 101 data for, 168 Arabinose -, 2,3,5-tri-O-benzyl-P-~-, I3C-n.m.r. -, D-, high-temperature transformation, acidic conditions, 216-211 data for, 168

SUBJECT INDEX

358

determination of enantiomeric form, 66 -, L-, in plant cell-wall hydrolyzates, liquid chromatography analysis, 55 liquid chromatography of, 33, 52-53 Aryl glycosides, photoinduced cleavage of, 182-183 Ascorbic acids -, L-, decarboxylation of, in acid solution, 289-290 liquid chromatography, 35-36 ultraviolet absorbances of, 65 Aspidosperma australe, 13 5-Azido-4-(hydroxymethyl)-1methoxynaphthalene esters, photocyclization of, 201 6-Azido-4-O-benzoyl-2,3,6-trideoxy-2fluoro-D-ribo-hexopyranosyl halide a bromide, IH- and 19F-n.m.r. data for, 126 chloride, 'H- and I9F-n.m.r. data for, 125 a iodide, 'H- and '9F-n.m.r. data for, 126 2-(2-Azidophenyl)ethyl alcohol, 200 2-(2-Azidophenyl)ethyl esters, photocyclization of. 201

B Bacillus macerans, 2 12, 215-2 17 cyclodextrin transglycosylase, 207 Bacteria, thermophilic, 21 I Bacterial polysaccharides complex, structural and sequence analysis of, 57 extracellular, liquid chromatography fractionation, 49 Benzoate ion, cyclodextrin inclusion complexes with, 221 Benzoic acid, cyclodextrin inclusion complexes with, 221, 223, 224 Benzoin, esters of, photocyclization of, 20 1 Benzoquinones, formation, 294 Benzoylacetic acid, cyclodextrin inclusion complexes with, 223, 224 Benzoyl-phenylmethanol (benzoin) esters, as protecting group, 200-201 I-(Benzylamin0)-l -deoxy-~-rhreo-2-hexulose, 320 I -(Benzylamino)- I-deoxy-~-nrabino-2hexulosuronic acid, 320

Benzyl ethers, photochemical cleavage of, in presence of bromine, 182-183 Benzyl glycosides, preparative liquid chromatography, 60 Biomass-conversion processes, carbohydrates in, analysis of, 52-54 Biomass materials, polysaccharides in, 306 Blood-group gl ycoproteins, oligosaccharides, liquid chromatography separation, 43 a-Bromo-2-nitrobenzyl polymer, 199 Browning, 307, 324 Bufadienolides, 13 Bufo, 13 Butanedione, 321 formation of 2,5-dimethylhydroquinone from, 294-295 from hydrothermolyzed cellulose, 304305 I-Butanol, cyclodextrin inclusion complexes with, 222-224 2-rert-Butylanthraquinone, for enhancing detectability of carbohydrates, 67 5-Butylbarbituric acid, cyclodextrin inclusion complexes with, 223, 224 5-Butyl-2-thiobarbituric acid, cyclodextrin inclusion complexes with, 223, 224 C

Carbohydrate anomers, separation of, 7071 Carbohydrate photochemistry, 180 Carbohydrate polymers, compositional analysis of, 54-57 Carbohydrates N-reacetylation, after methanolysis, 256 separation on cation-exchange columns, mechanisms, 26 sequence. liquid chromatography methods for determining, 57-58 structure, liquid chromatography methods for determining, 57-58 Carbonyl-amine reaction, formation of N substituted aldosylamine by, 308 Carbonyl derivatives, photosensitive protecting groups, 195-202 Carboxylic acids free, photochemical release of, from a 2-

SUBJECT INDEX

359

nitrobenzyl-substituted poly(viny1 oligosaccharides, liquid chromatography alcohol), I99 separation, 42-43 protection of, 198-202 sialylated oligosaccharides, fractionaK-Carrageenan, oligomers, liquid chromation, 46 tography, 40 Chemical processes, carbohydrate transCartilage, glycosaminoglycans, analysis, 56 formation in, 323-326 Catechol, 295 Chitin as enzyme inhibitor, 326 hydrolyses, neutral, N-acetylated anaCathepsin, isolation of carbohydrates logs from, liquid chromatography, from, on analytical-scale columns, 60 41 Cathepsin-B, glycopeptides, liquid chromaoligosaccharides, liquid chromatography, tography separation, 48 39-40 Cathepsin-D, glycopeptides, liquid chroma- 3-Chlorobenzoylacetic acid, cyclodextrin tography separation, 48 inclusion complexes with, 223, 224 Cellobiose 6-Chloro-5,6-dideoxy-5,6-difluoro1,2-0alkaline degradation, product pattern, isoprop ylidene-3-0-meth yl-a-D-xylo302 hex-5-enofuranose hydrolysis of, 299 -, isomer, 13C-n.m.r.data for, 176 liquid chromatography methods for -, (2)isomer, I3C-n.m.r. data for, 176 analysis of, 33 3-Chlorophenyl acetate, cyclodextrin Cellobiouronic acid, hydrolysis of, 299 inclusion complexes with, 223, 224 Cellobiulose, liquid chromatography methChondroitin, disaccharides, liquid chromaods for analysis of, 33 tography, 37 Cello-oligosaccharides, liquid chromatogra- Chondroitin sulfate phy, 39 composition, analysis, 55 peak-area analyses, 64 oligosaccharides from, sulfation patpreparative, 60 terns, 49 Cellulases, mode of action, analysis of, 54 structural and sequence analysis of, 57 Cellulose Chondroitin 6-sulfate, conformational acid-catalyzed hydrolysis of, mechanism inversion, 7 of, 298-299 "C-n. m. r. spectroscopy acid hydrolysis of, 297-298 chemical shifts, 77 alkaline degradation of, products, 304 "C-r~.m.r.-~~F coupling constants, 77-78 alkaline peeling of, 301-303 'J ( I T , I9F),77-78 high-temperature transformation of, 2J ( I T , I9F), 78 alkaline conditions, 300-305 ("C, I9F),78 hydrothermolysis of, 299-300 4J ( I T , I9F),78 liquid chromatography analysis, 39 Coformycin analogs, 28 non-fermentable oligosaccharides, liquid Copper bis(phenanthroline), for enhancing chromatography methods for, 52 detectability of carbohydrates, 67 stopping reaction involving, 302-303 Corn syrup, oligosaccharides, liquid chrostructure, 297 matography analysis, 39 Cellulosic materials, yellowing of, by Cotton fibers, liquid chromatography aging, 324-325 analysis, 52 Cellulosine, 21 1 Crystalline dextrins, 211-213 Ceruloplasmin Cuprammonium, for enhancing detectabilglycopeptides, liquid chromatography ity of carbohydrates, 67 separation, 48 Curacin, 14 isolation of carbohydrates from, on o-Curacose, 14 analytical-scale columns, 60 Curamycin, 14

(a

360

SUBJECT INDEX

Curamycose, 14 Cyanoacetamide, for enhancing detectability of carbohydrates, 67 3-Cyanophenol, cyclodextrin inclusion complexes with, 221 4-Cyanophenol, cyclodextrin inclusion complexes with, 221 3-Cyanophenolate ion, cyclodextrin inclusion complexes with, 221 4-Cyanophenolate ion, cyclodextrin inclusion complexes with, 221 Cyclic acetals, as photosensitive protecting groups, 195 Cyclic adenosine monophosphate, 2nitrobenzyl and 6-nitroveratryl esters of, irradiation of, 204 Cyclic guanosine monophosphate, 2nitrobenzyl and 6-nitroveratryl esters of, irradiation of, 204 Cyclobarbital, cyclodextrin inclusion complexes with, 223, 224 Cyclodextrin alpha, 206 chemical synthesis of, 207 conformational change of, during complex-formation, 230-23 1 dipole moment, 232 D-glucosyl units, 228 inclusion-complexes, enthalpy-entropy compensation for, 224 strained, high-energy conformation, 228 beta, 206 chemical structure, 207 inclusion-complexes, enthalpy-entropy compensation for, 224 numbering of atoms of, 207 partially methylated, 245 branched, 246 I F c.p.-m.a.s. studies of, 231 cavity, water of, 227-228 chiral discrimination by, 247-249 covalent capping of, 247 2,6-di-O-methyl derivative, 245 discovery of, 211-213 enthalpy of association, 228 facilitation of association of molecules through presence of, 210 formation of, from starch, 215-217 further research in, 249

gamma, 206 modified, 245-246 space regulation of cavity by a p pended naphthalene moiety, 246 substitution with two naphthyl groups, 246-247 D-glucosyl residues, 214 liquid chromatography separation, 44-45 modified catalytic properties, 244-247 c h i d selectivity of, 249 complexing ability, 245 molecules, covalent linking of two, 245 periodate oxidation of, 214-215 physical properties of, 208 properties, 206 reactions capable of catalysis by, c h i d selectivity, 248-249 reactions catalyzed, 244 separation, 207 structural and sequence analysis of, 57 structure of, determination of, 213-215 -, tri-0-methyl-a-, 245 ultrasonic-relaxation techniques for, 230 Cyclodextrin inclusion complexes, 205-250 acid-base titration, 220 advantage of, 208 with azo dyes, 235, 239 with biphenyl compounds, 239 with cinnamates, 239 circular dichroism, 219-220 complex-formation detection of, 219-220 enthalpy-entropy compensation, 221225 favorable entropy change in, 233 hydrophobic interactions in, 233 kinetics of, 234-244 in nonaqueous solvents, 226 solvation changes on complexation, 225-226 standard-enthalpy change accompanying, 220-223 standard-entropy change, 220-223 standard free-energy decrease associated with, 220 thermodynamics of, 220-234 conformational change, 236, 238-239 cross-polarization, magic-angle-spinning, 13C-n.m.r. spectroscopy, 219

36I

SUBJECT INDEX crystal structure analyses, 232-233 with Crystal Violet, 241 with cyanine dyes, 244 discovery of, 217 electric-field pulse relaxation, 234 fluorescence, 219 formation of, 210-211 kinetics, 237-238 IH-nuclear magnetic resonance spectroscopy, 218 hydrophobic interactions, 226-227 with inorganic anions, 235-236 isoequilibrium, 221-225 with long-chain fatty acids, 240 with Methyl Orange, 242-244 nuclear magnetic resonance, 220 one-host-one guest complex-formation,

235-239 one host-two guests complexation, 209-

210,240-243 mechanisms, 21I with Methyl Orange, 245 with organic dyes, 235,240-242 phosphorescence decay, 235 properties, 217-218 with Pyronine Y,240 with Roccellin, 244 Saenger's theory of formation, 229 single-step, binding mechanism, 237 solubility, 220 stability, 208-209 dependence on polarizability of guest molecule, 232 stopped-flow kinetic studies, 234,237-

238 temperature, 225 temperature-jump relaxation kinetic studies, 234,237-238,240 with Tropaeolin, 242,244 two-dimensional, nuclear Overhauser effect experiment on, 218-219 two hosts-one guest complex formation,

239-240 two hosts-two guests complex-formation, 242-244 two-step mechanism, 238-239 ultrasonic absorption relaxation, 234 ultraviolet-visible absorption, 219 van der Waals forces in, 231-233 X-ray crystallography, 218

Cyclodextrin transglycosylase, 207-208 Cyclohexanecarboxylic acid, cyclodextrin inclusion complexes with, 221 Cyclohexanol, cyclodextrin inclusion complexes with, 222-224 Cyclomaltoheptaose, 206 Cyclomaltohexaose, 206 Cyclomaltohexaose inclusion complexes, standard formation enthalpies and entropies of, 221-223 Cyclomalto-octaose, 206 Cyclomalto-oligosaccharides.See also C yclodextrins branched, 246 liquid chromatography separation, 44-45 Cyclopentenones, formation, 294 Cyclosophoroses liquid chromatography separation, 44-45 preparative liquid chromatography, 60 L-Cysteine, and a-dicarbonyl compounds, reaction between, 318 DL-Cysteine, with D-galactose, products from, 317-318 D

Dansylhydrazones, liquid chromatography, pre-column derivatization procedures,

68,68 1-Deoxy-1-(dibenzylamino)-~-arabino-2hexulosuronic acid, 320 3-Deoxy-3-C-(mono or di)fluoromethyleneD-hexo(or pento)furanoses, 'H-and 19F-n.m.r. data for, 140-141 6-Deoxy-6,6-d~uorogalactopyranose -, 1,2:3,4-di-O-isopropylidene-a-~-, 'Hand 19F-n.m.r. data for, 151 -, 1,2,3,4-tetra-O-acetyI-~-, IH-and 19F-n.m.r. data for, 150-151 2-Deoxy-2,2-difluoro-~-ara bino-hexopyranose a anomer, 'Hand I9F-n.m.r. data for,

149 p anomer, IH-and 19F-n.m.r. data for, 149 2-Deoxy-2-fluoro-~-arab~nofuranose -, l-O-acetyl-5-0-benzoyl-3-O-formyla-,IH- and 19F-n.m.r. data for, 110 -, 5-0-benzyl-, IH-and I9F-n.m.r. data for, 110

362

-,

SUBJECT INDEX

3-Deoxy-a-~-erythro-hex-2-enopyranosyl 1,3-di-O-acetyl-5-O-benzoyl-a-, 'Hfluoride and I9F-n.m.r. data for, I10 -, 2,4,6-tri-O-acetyl-, 'H- and I9F-, 1,3-di-O-acetyl-5-O-benzyl-, 'H- and n.m.r. data for, 134 I9F-n.m.r. data for, I10 -, 2,4,6-tri-O-benzoyl-, 'H- and I9F-, 1,3-di-O-benzoyl-5-O-benzyl-, 'Hand I9F-n.m.r. data for, 110 n.m.r. data for, 134 4-Deoxy-~-glycero-2,3-hexodiulose, 292 -, Sphosphate, sodium salt, 'H- and 6-Deoxyhexopyranose derivatives, fluori19F-n.m.r. data for, 109 nated, 'H- and '9F-n.m.r. data for, -, 1,3,5-tri-O-benzoyl-(y-, 'H- and I9F132-133 n.m.r. data for, 110 -, 1,3,5-tri-O-benzyl-c-, 'H- and I9F3-Deoxy-~-erythro-hexosulose, 292 3-Deoxy-~-erythro-hexos-2-ulose, forman.m.r. data for, 110 2-Deoxy-2-fluoro-a-~-arabinofuranosyl tion, 310-311 bromide 3-Deoxyhexos-2-ulose, formation of, 3 11 -, 3-O-acetyl-5-O-benzoyl-, 'H- and 6-Deoxylglucose, liquid chromatography I9F-n.m.r. data for, 138 methods for analysis of, 33 -, 3,5-di-O-benzoyl-, 'H- and I9F-n.m.r. Deoxy-2-octulosonic acids, liquid chromadata for, 138 tography, 36-37 5-Deoxy-5-fluoro-a-~-g~ucofuranurono-6,3Deoxypentofuranose derivatives, fluorilactone, 1,2-O-isopropylidene-, I3Cnated, 'H- and I9F-n.m.r. data for, 138 n.m.r. data for, 170 2-Deoxypentopyranosy1 fluorides, 'H- and Deoxyfluorohexofuranoses, "C-n.m.r. data 19F-n.m.r. data for, 137 Deoxy sugars for, 165-167 acid decomposition, 252 2-Deoxy-2-fluorohexopyranosyl fluorides, 'H- and I9F-n.m.r. data for, 146-147 Liquid chromatography, 31, 33 3(or 4, or 6)-Deoxy-3(or 4, or 6)-fluorohex- Dermatan sulfate, composition, analysis, 55 opyranosyl fluorides, IH- and I9FDeulofeu, Venancio n.m.r. data for, 148-149 5-Deoxy-5-fluoro-p-~-idofuranurono-6,3- academic career, 12 awards and honors, 14 lactone -, 1,2-O-benzylidenebook, 13 Doctoral Thesis, 11 I3C-n.m.r. data for, 170 at E. R. Squibb & Sons, 12, 14 IH- and 19F-n.m.r. data for, 116 editorial work, 14 'H- and 19F-n.m.r. data for, 116 education, 11 -, 1,2-O-isopropylidene"C-n.m.r. data for, 170 family, 11 publications, 13 'H- and I9F-n.m.r. data for, 116 research, 11-13 5-Deoxy-5-fluoro- 1,2-O-isopropylidene-a~-g~ucofuranurono-6,3-lactone, 'HDextrans branching patterns of, 41 and 19F-n.m.r.data for, 116 3-Deox y-3-fluoroxylop yranose liquid chromatography analysis, 39 'H- and '9F-n.m.r. data for, 105 3,6-Dideoxy-3,6-difluoro-P-~-allopyrano-, 1,2,4-tri-O-acetyl-~-,IH- and I9Fside n.m.r. data for, 105 -, methyl 2-Deoxy-2-halogenohexopyranosyl fluoI3C-n.m.r. data for, 175 rides, 'H- and I9F-n,m.r. data for, 'H- and 19F-n.m.r. data for, 149 I 129 -, methyl 2,4-di-O-benzoyl-, IH- and I9F-n.m.r. data for, 149 2-Deoxy-2-halogenopentopyranosylfluorides, 'H- and I9F-n.m.r. data for, -, p-nitrophenyl, 'H- and 19F-n.m.r. data for. 150 135- 137

SUBJECT INDEX

363

formation of pyranones from, 280 -, phenyl formation of substituted acetophenones I3C-n.m.r. data for, 175 from, 280 IH-and I9F-n.m.r. data for, 150 high-temperature transformation, in 1,6-Dideoxy- 1,6-difluoro-2,3:4,6-di-Oalkali conditions, 284 isopropylidenegalactitol,'H- and I9Freaction of, with amino acids, 321 n.m.r. data for, 159 I ,6-Dideoxy-l,6-difluoro-galactito1, IH-and 2,3-Dihydroxyacetophenone,290 1,2-DihydroxyacroIein. See Triose-reducI9F-n.m.r. data for, 158 tone Dideoxydifluorohexopyranoses, 'H- and 3,8-Dihydroxy-2-methylchromone, formaI9F-n.m.r. data for, 149-151 tion, 290-291 Dideoxydifluorohexopyranosides, 'H- and 6,7-Dihydroxyphthalide, 290 I9F-n.m.r. data for, 149-151 Diisopropyl phosphorofluoridate, cyclodex5,6-Dideoxy-6,6-difluoro1,2-O-isopropylitrin inclusion complexes with, 222, dene-a-D-xylo-hex-Senofuranose 224 -, 3-O-benzyl-, I3C-n.m.r. data for, 175 -, 3-O-methyl-, 13C-n.m.r.data for, 176 Diketosamines, mechanism for cleavage of, 309-311 2,3-Dideoxy-2-fluoro-hexopyranosides, IH3,5-Dimethoxy-a,a-dimethylbenzyloxycarand 19F-n.m.r. data for, 131-132 bony1 groups, photochemical removal 2,6-Dideoxy-2-fluorohexopyranosyl fluoof, 192 rides, IH- and I9F-n.m.r. data for, 153 3,4-Dideoxy-~-g~ycero-hex-3-enopyranosyl3,5-Dimethoxybenzyloxycarbonylgroup, photochemical removal of, 192 fluoride 2.5-Dimethyl-I ,4-benzenediol, from hy-, 6-O-acetyl-2-ulose, 'H- and I9Fdrothermolyzed cellulose, 304-305 n.m.r. data for, 134 2,5-Dimethylbenzoquinone -, 6-O-benzoyl-2-ulose, IH-and 19Fformation, 294 n.m.r. data for, 134 from hydrothermolyzed cellulose, 3045,6-Dideoxy- 1,2-O-isopropylidenehex-5305 enofuranose photo6-chloro-5,6-difluoro-3-O-methyI-a-3,4,3',4'-Dimethylenedioxybenzoin, cyclization of, 201 D-xylo-,'H- and 19F-n.m.r. data for, N,N-Dimethylhydrazones, 197 154 -, 6,6-difluoro-3-O-methyl-a-D-ribo-, photosensitized decomposition of, in presence of oxygen, 198 IH- and 19F-n.m.r. data for, 154 -, 6,6-difluoro-3-0-methyl-f3-~-xylo-, 2.2-Dimethyl- I-propanol, cyclodextrin inclusion complexes with, 222-224 IH- and I9F-n.m.r. data for, 154 -, 6,6-difluoro-3-O-methyl-a-~-xyb,Dimethylthiocarbamates, photochemical cleavage, 189- 190 IH-and 19F-n.m.r. data for, 154 6-O-(Dimethylthiocarbonyl)-1,2:3,4-di-0Difluorinated hex-5-enofuranoses, IH- and isopropylidene-a-D-gdactopyranose, 19F-n.m.r. data for, 154 photochemical cleavage of, 190 Dihydropyrrolopyrazine, formation of, 3 14 2,4-Dihydroxy-2-(hydroxymethyl)butanoic 2,4-Dinitrobenzenesulfenicesters photolysis of esters, 200 acid, 305 as protecting groups for carboxyl Dihydroxyacetone, 321 groups, 200 formation of aromatics from, in acid 3.5-Dinitrophenyl phosphoric esters, phosolution, 279-280 tohydrolysis, 203 formation of benzofuran from, 280 Diols, protection of, 188-189 formation of hydroxydimethylpyranoI ,4-Dioxane, cyclodextrin inclusion compyrandiones from, 280 plexes with, 222, 224 formation of 3-hydroxy-6-methyl-4H1,2-Diphenylethylene dithioacetals, 196 pyran-4-one from, 280

-.

364

SUBJECT INDEX

photochemical decomposition of, in presence of oxygen, 197 Disaccharides in dairy products, liquid chromatography separation, 52 ionic, high-performance liquid chromatography, 33-37 large-scale preparative liquid chromatography, 62 neutral, analytical high-performance liquid chromatography, 32 preparative liquid chromatography, 60 sulfated, liquid chromatography, 37 Doisy, E.A., 12

Europium salts, for enhancing detectability of carbohydrates, 67

F Fagara COCO, 13 y-Fagarine, 13 Fast-atom-bombardment ionization, 70 Fermentation, 323 Fetuin hydrolysis. with trifluoroacetic acid,

268 methanolysis, 258 sialylated oligosaccharides, fractionation, 46 E Fibronectin oligosaccharides, liquid chromatography Endo-glucanases, mode of action, analysis separation, 42-43 of, 54 sialylated oligosaccharides, fractionaEnones, formation of, 326 tion, 46 Enzymic hydrolysis, of glycosidic linkages, Flip-flop hydrogen bond, 228 270-271 3-F~uoro-~-g~ucofuroses, 3-C-branched, D-Erythrose, 321 IH- and 19F-n.m.r. data for, 138-140 formation of aromatics from, 277-278 I9F-n.m.r. spectroscopy formation of y-pyranone from, 277-278 19F-chemicalshifts, 78-80 high-temperature transformation of, in I9F-I9F coupling, 80 alkali solution, 283 Food processing, color-stopping reaction Escasany, Irene, 12 in, 324-325 Esters, protection as, 189-191 Foods Ethanol carbohydrates in cyclodextrin inclusion complexes with, analysis of, 50-52 222, 224 soluble, liquid chromatography methfermentation sources, 326 ods for, 51 Ethers, protection as, 181-182 discoloration of, 324-325 5-Ethylbarbituric acid, cyclodextrin incluFormaldehyde, 321 sion complexes with, 223, 224 Formic acid, 296 Ethylenediamine, for enhancing detectabilcyclodextrin inclusion complexes with, ity of carbohydrates, 67 221 Ethylene dithioacetals, 196 liquid chromatography, 53-54 1 -Ethyl-2-formyl-5-methylpy1role, formaFormolysis, for cleavage of glycosidic tion of, 313-314 linkages, 269-270 3-Ethyl-2-hydroxycyclopent-2-en-l-one, 2-Formyl-5-(hydroxymethyl)-l-methylpyrformation, 294 role, 314 3-Ethylphenyl acetate, cyclodextrin incluformation of, 312-314 sion complexes with, 223, 224 2-Formyl-5-(hydroxymethyl)pyrrole-1 Ethyl 2,3,6-trideoxy-6-fluoro-ci-~-erythroacetic acid, formation of, 312-314 hexopyranoside 6,[2-Formyl-5-(hydroxymethyl)pyrrol-l-, 4-O-acetyl-, 'H- and 19F-n.m.r. data yllnorleucine, formation of, 314 for, 135 2-Formyl-5-methylpyrrole-l-acetic acid, -, 4-O-benzyl-, 'H- and I9F-n.m.r. data formation of, 312-314 for, 135 2H,5H-6-Formyl-3-oxopyrrolo[ 1 ,2-a]pyra-

SUBJECT INDEX

365

zin-4-acetic acid, formation of, 312D-Fructose 314 and L-alanine, products from, 319 D-Fructans, hydrolysis, 269 alkaline degradation of, 292 D-Fructofuranose base-degraded solution, products, 294 -, 6-0-benzoyl- I-deoxy-l-fluoro-2,3-0in food, liquid chromatography separaisopropylidene-p-, IH-and I9Ftion, 52 n.m.r. data for, 144 formation of 2-(2-hydroxyacetyl)furan -, 6-deoxy-6-fluoro-2,3-O-isopropylifrom, 286-287 dene- 1-0-p-tolylsulfonyl-pheated neutral solutions of, antimicrobial 13C-n.m.r.data for, 174 activity formed in, 326 IH- and I9F-n.m.r. data for, 145 phenols from, 290 -, I,6-dideoxy-l,6-difluoro-2,3-0thermolysis of, in acid solution, prodisopropylidene-pucts, 286 13C-n.m.r. data for, 174 Fucose, liquid chromatography methods IH- and 19F-n.m.r. data for, 145 for analysis of, 33 D-Fructofuranoside D-Fucose, 4-O-methyl-. See D-Curacose -, methyl l-deoxy-l-fluoroFukumi, H., 6 a anomer, 13C-n.m.r.data for, 174 2-Furaldehyde p anomer, l3C-n.m.r. data for, 174 -, 5-(hydroxymethy1)-,323 -, 3,4,6-tri-O-benzoyl-p-, 13C-n.m.r. formation of, 318 data for, 174 from pentoses, 275-276 -, methyl 3,4-di-O-acetyl-l,6-dideoxy- liquid chromatography, 53-54 1,bdifluorotechnical importance, 323 a anomer, IH- and 19F-n.m.r. data for, D-Furanose 145 -, 3-deoxy-3-C-(difluoromethylene)-1,2p anomer, 'H- and I9F-n.m.r. data for, O-isopropylidene-a145 -, ribo-hexo-, IH- and 19F-n.m.r. data -, methyl 1,6-dideoxy-l ,6-difluorofor, 141 a anomer, 13C-n.m.r. data for, 174 -, erythro-pentodialdo-1,4-furanose, p anomer, W-n.m.r. data for, 174 IH- and I9F-n.m.r. data for, 141 -, methyl 3,4,6-tri-O-benzoyl-l-deoxy- Furans I-fluorofrom carbohydrates, 323 a anomer, IH- and 19F-n.m.r. data for, formation of, 326 145 Furfurylidene-P-pyranone p anomer, IH-and 19F-n.m.r. data for, chromophoric, 322 145 formation of, in presence of methanol, Fructo-oligosaccharides, liquid chromatog322-323 raphy, 39 2-Furoic acid, conversion of, into methyl D-Fructopyranose 5-nitro-2-furoate, 289 -, 4-deoxy-4-fluoro-pN-(2-Furoylmethyl)-~-alanine, 3 19 W-n.m.r. data for, 173 2-(2-Furylidene)-4-hydroxy-5-methyl-3(2iY)IH- and I9F-n.m.r. data for, 144 furanone, 322 -, 1-deoxy-l-fluoro-2,3:4,5-di-O-isopropylideneW-n.m.r. data for, 173 IH- and 19F-n.m.r. data for, 144 G Fructose large-scale preparative liquid chromatog- Galactitol, liquid chromatography methods for analysis of, 33 raphy, 62 liquid chromatography methods for l-yl)-4-thiazolidinecarboxy2-(~-Galactitoltic acid, diastereomers, 317-318 analysis of, 33

366

SUBJECT INDEX

f3 anomer, IH- and 19F-n.m.r. data for, D-Galactofuranose 95 -, I-O-acetyl-2,3,5,6-tetra-O-benzoyl-4-, 1,2:3,4-di-O-isopropylidene-a-, IHfluoro-p-, I3C-n.m.r. data for, 172 and lyF-n.m.r. data for, 95 -, 3-deoxy-3-fluoro- 1,2:5,6-di-O-isopro-, 1,2:3,4-di-O-isopropylidene-6-Opylidene-a-, 'H- and 19F-n.m.r. data [(methylthio)thiocarbonyl]-a-, phofor, 99 tochemical cleavage of, 190 D-(;alactofuranosyl fluoride -, I ,2:3,4-di-O-isopropylidene-6-O-, 2,3,5,6-tetra-O-acetyl-, 'H- and I9Fnitro-a-, photolysis of, 191 n.m.r. data for, 97 -, I ,2:3,4-di-O-isopropylidene-6-O-p-, 2,3,5,6-tetra-O-benzoyl-a-, IH- and l9F-n.m.r. data for, 97 tolylsulfonyl-a-, photolysis of, 191 -, 1,2,4,6-tetra-O-acetyl-3-deoxy-3L-Galactofuranosyl fluoride fluoro-, 3,6-dideoxy-pa anomer, I3C-n.m.r. data for, 162 -, 3-azido-5-O-benzoyl-2-O-benzyl-, p anomer, "C-n.m.r. data for, 162 'H- and 19F-n.m.r. data for, 127 top yranose -, 3-azido-5-O-benzoyl-2-O-methyl-,~-Galac -, 2,6-dideoxy-2-fluoro'H- and I9F-n.m.r. data for, 127 a anomer, IH- and I9F-n.m.r. data for, -, 5-O-benzoyl-2-O-benzyl-3-(triI32 fluoroacetamido)-, IH- and I9Ff3 anomer, IH- and 19F-n.m.r. data for, n.m.r. data for, 128 I32 -, 5-O-benzoyl-2-O-methyl-3-(tri-, 1,3,4-tri-O-acetyl-p-, 'H- and I9Ffluoroacetamido)-, 'H- and I9Fn.m.r. data for, 132 n.m.r. data for, 128 -, 2,3,6-trideoxy-2-fluoroGalactoglucomannans, 305 -, 1-0-acetyl-4-0-benzoyl-2-fluoro-3Galactonic acids, analytical high-perfor(trifluoroacetamido)-p-, 'H- and mance liquid chromatography, 34 I9F-n.m.r. data for, 124 D-Galactop yranose -, 3-amino-, 'H- and '9F-n.m.r. data -, 2-acetamido-l,3,4-tri-O-acetyl-2,6for, 124 dideoxy-6-fluoro-, IH- and 19F-n.m.r. D-Galactop yranoside data for, 120 -, benzyl 3,4,6-tri-O-benzyl-2-deoxy-2-, 2-deoxy-2-fluorofluoro-p-, "C-n.m.r. data for, 161 a anomer, 'Hand 19F-n.m.r. data for, -, 2-deoxy-2-fluoro85 -, methyl p-, 'H- and "F-n.m.r. data p anomer, 'H- and I9F-n.m.r. data for, for, 86 85 -, methyl 3,4-O-isopropylidene-6-0-, 1,3,4,6-tetra-O-acetyl-, IH- and trityl-p-, IH- and IyF-n.m.r. data I9F-n.m.r. data for, 85-86 for, 86 -, 3-deoxy-3-fluoro-, 1,2,4,6-tetra-O-, trifluoromethyl 3,4,6-tri-O-acetyIacetyl-, 'Hand 19F-n.m.r. data for, a-, 'H- and I9F-n.m.r. data for, 86 90 -, 3-deoxy-3-fluoro-, methyl 2,4-di-O-, 4-deoxy-4-fluoroa anomer, I3C-n.m.r. data for, 163 benzoyl-6-O-(bromoacetyl), IH- and 19F-n.m.r. data for, 90 p anomer, I3C-n.m.r. data for, 163 -, 1,2,3,6-tetra-O-acetyl-p-, IH-and -, 4,6-dideoxy-4,6-difluoro'9F-n.m.r. data for, 92 -, methyl, 'H- and '9F-n.m.r. data -, I ,3,4,6-tetra-O-acetyl-2-deoxy-2for, 150 -, phenyl a-,'H- and I9F-n.m.r. data fluoro-a-, 13C-n.m.r. data for, 161 -, 6-deoxy-6-fluorofor, 150 -, methyl 2-acetamido-2,4,6-trideoxya anomer, 'H- and I9F-n.m.r. data for, 95 4.6-difluoro-a-

SUBJECT INDEX

-,

3-O-acetyl-, IH- and I9F-n.m.r. data for, 157 IH- and 19F-n.m.r. data for, 157 -, methyl 2-benzamido-2,4,6-trideoxy4,6-difluoro-a-, 3-O-acetyl-, 'H- and I9F-n.m.r. data for, 157 -, 3-O-benzyl-, IH- and 19F-n.m.r. data for, 157 -, methyl 2-deoxy-2-fluorop anomer, 13C-n.m.r.data for, 161 -, 3,4,6-tri-O-acetyl-p-, I3C-n.m.r. data for, 161 -, methyl 3-deoxy-3-fluorop anomer, 13C-n.m.r.data for, 162

367

-, 2-acetamido-, IH- and I9F-n.m.r. data for, 120 -, 2-acetamido-3,4-di-O-acetyl-, IHand I9F-n.m.r. data for, 120 -, 2-benzamido-, IH- and I9F-n.m.r. data for, 120 -, 2-benzamido-4-O-benzoyl-3-0benzyl-, 'H- and 19F-n.rn.r. data for, 121 -, 2-benzamido-3-O-benzyl-, 'H- and I9F-n.m.r. data for, 121 -, 3,4-di-O-acetyl-2-benzamido-, 'Hand I9F-n.m.r. data for, 120 L-Galactopyranoside -, benzyl 2,3,6-trideoxy-2-fluoro-p-, 2,4-di-O-benzoyl-6-O-(bromoace-, 3-amino-, 'H- and I9F-n.m.r. data ty1)-, I3C-n.m.r.data for, 162-163 for, 124 -, 2,4,6-tri-O-acetyl-P-, "C-n.m.r. -, 3-benzamidodata for, 162 13C-n.m.r.data for, 171 -, methyl 4-deoxy-4-fluoroIH- and I9F-n.m.r. data for, 124 a anomer, 13C-n.m.r.data for, 163 -, 4-O-benzoyl-3-(trifluoroace(3 anomer, I3C-n.m.r. data for, 163 tamido)-, 6-O-benzoyl-2,3-di-O-benzyl-p-, I3C-n.m.r. data for, 171 IH- and 19F-n.m.r. data for, 93 'H- and I9F-n.m.r. data for, 124 -, 2,3-di-O-benzyl-p-, I3C-n.m.r.data -, 3-(trifluoroacetamido)-,'H- and for, 164 I9F-n.m.r. data for, 124 -, 2,3-di-O-benzyl-6-O-trityl-p-, I3C-, methyl 6-deoxy-2,3-di-O-p-~-galacton.m.r. data for, 164 pyranosyl-a-, synthesis of, utiliza-, 2,3-di-O-trityl-P-, IH- and I9Ftion of 2-nitrobenzylidene protecting n.m.r. data for, 93 group in, 188-189 -, 2,3,6-tri-O-acetyl-, I3C-n.m.r.data -, methyl 2,3,6-trideoxy-2-fluoro-pfor, 164 -, 3-amino-, I3C-n.m.r.data for, 171 -, 2,3,6-tri-O-acetyl-u-, 'H- and 19F-, 3-benzarnido-4-O-benzoyl-, I3Cn.m.r. data for, 93 n.m.r. data for, 171 -, 2,3,6-tn-O-benzoyl-p-, IH- and -, 3-(trifluoroacetamido)-,I3C-n.m.r. 19F-n.m.r. data for, 93 data for, 171 -, methyl 6-deoxy-6-fluoro-, methyl 2,3,6-trideoxy-2-fluoroa anomer, 'H- and I9F-n.m.r. data for, -, 3-amino-p-, IH- and 19F-n.rn.r. 95 data for, 124 P anomer, 13C-n.m.r. data for, 164 -, 3-benzamido-p-, 'H- and I9F-, 1,2,3,4-tetra-O-acetyI-a-, IH- and n.m.r. data for, 125 I9F-n.m.r. data for, 95 -, 3-benzamido-4-O-benzoyl-p-, IH-, 2,3,4-tri-O-acetyl-P-, I3C-n.m.r. and 19F-n.m.r. data for, 125 data for, 164 -, 3-(trifluoroacetamido)-, 'H- and -, 2,3,4-tri-O-acetyl-a-, IH- and I9F19F-n.m.r. data for, 125 n.m.r. data for, 95 -, trifluoromethyl 3,4-di-O-acetyl-2,6-, methyl 4,6-dideoxy-4,6-difluorodideoxy-a-, 'H- and I9F-n.m.r. Q anomer, I3C-n.m.r.data for, 175 data for, 132 p anomer, I3C-n.m.r.data for, 175 L-Galactopyranos yl bromide, 4-0-benzoyl-, methyl 2,6-dideoxy-6-fluoro-a2,3,6-trideoxy-2-fluoro-3-(trifluoroacet-

368

SUBJECT INDEX

Gasification, 273-274, 323 amido)-a-, IH- and I9F-n.m.r. data for, 125 Gentiobiose, liquid chromatography methods for analysis of, 33 D-Galactopyranosyl chloride, methyl 2,4Glucans, cyclic, 60 di-O-benzoyl-6-0-(bromoacety1)-3Glucitol, liquid chromatography methods deoxy-3-fluoro-a-, W-n.m.r. data for, for analysis of, 33 172 D-Glucofuranose Galactopyranosyl fluoride -, 1-0-acetyl-2,3,5,6-tetra-O-benzoyl-4-, 2-deoxy-2-fluoro-~fluoro-p-, W-n.m.r. data for, 172 a anomer, IH- and I9F-n.m.r. data for, -, 3,6-anhydro-5-deoxy-5-fluoro1,2-0I46 -, 3,4,6-tri-O-acetyl-, 'H- and t9Fisopropylidene-a-, IH- and I9Fn.m.r. data for, 115 n.m.r. data for, 146 -, 3,6-anhydro-5-deoxy-5,6,6-trifluoro-, 2,6-dideoxy-2-fluoro-~a anomer, IH- and I9F-n.m.r. data for, 1,2-0-isopropylideneI3C-n.m.r. data for, 177 153 -, 3,4-di-O-acetyl-, 'H- and 19FIH- and I9F-n.m.r. data for, 158 n.m.r. data for, 153 -, 3,6-anhydro-6,6-difluoro-, 2,3,4,6-tetra-O-acetyI-~-, I ,2-0-benzylidene-a-, IH- and I9Fa anomer, 13C-n.m.r.data for, 160 n.m.r. data for, 152 p anomer, Wn.m.r. data for, 160 -, 1,2-0-isopropylidene-a-, IH- and 'H- and 19F-n.m.r. data for, 82 19F-n.m.r.data for, 152 -, 2,3,6-tri-0-acetyl-4-deoxy-4-fluoro-D- -, 3,6-anhydro-6,6-difluoro-aa anomer, IH- and I9F-n.m.r. data for, -, 1,2-0-benzylidene-, Wn.m.r. 148 data for, 175 p anomer, IH- and 19F-n.m.r.data for, -, 1,2-0-isopropylidene-, "C-n.m.r. 148 data for, 175 -, 3,4,6-tri-O-acetyl-2-deoxy-~-, 3-deoxy-3-fluoro-, 2-bromo-, IH- and f9F-n.m.r.data -, 3-C-(acetoxymethyl)-I ,2-0-isoprofor, 129 pylidene-a-, IH- and i9F-n.m.r. -, 2-iodo-, IH- and I9F-n.m.r. data data for, 138 for, 129 -, 6-0-benzoyl- 1,2-0-isopropylidene-, 3,4,6-trideoxy-3,4,6-trifluoro-a-~a-,IH- and I9F-n.m.r. data for, I3C-n.m.r. data for, 177 I39 'H- and I9F-n.m.r. data for, 158 -, 3-C-[1,2-di(hydroxyethyl)]-1,2:5,6Galactose di-0-isopropylidene-a-, IH- and -, DI9F-n.m.r. data for, 139 in plant cell-wall hydrolyzates -, 1,2:5,6-di-O-isopropylidene-a-, IHand I9F-n.m.r. data for, 99, 138, liquid chromatography analysis, 55 139 determination of enantiomeric form, 66 liquid chromatography, 33, 52-53 -, 1,2:5,6-di-O-isopropylidene-3deoxy-3-fluoro-a-, I3C-n.m,r. data D-GalaCtOSe diethyl dithioacetal, photofor, 166 chemical decomposition of, 197 Galacturonic acid -, 1,2:5,6-di-O-isopropylidene-3-Cacid hydrolysis of, correction factors, (methoxycarbony1)-a-, IH- and 254 19F-n.m.r.data for, 140 -, D-, 3-C-(ethoxyallyl)-1,2-0-isopropyliin mosses, 324 dene-a-, IH- and I9F-n.m.r. data phenols from, 290 for, 139 treated with trifluoroacetic acid. recover3-C-[(ethoxycarbonyl)(formylies of, 261-262 imino)methyl]-1,2:5,6-di-0-

-.

SUBJECT INDEX

369

and I9F-, 2,5-di-O-benzoyl-p-, 'H- and I9Fisopropylidene-a-, 'Hn.m.r. data for, 139 n.m.r. data for, I16 Glucoisosaccharinic acid -, 3-C-[ethoxy(ethoxycarbonyl)(formylamino)methyl]-l,2:5,6-di-O- formation of, 292 structure, 291 isopropylidene-a-, IH- and 19FGlucometasaccharinic acid, structure, 291 n.m.r. data for, 139 -, 3-C-(hydroxymethyl)-1,2:5,6-di-O- -, D-,formation of, 292, 303 D-Gluconic acid isopropylidene-a-, 'H- and I9Fanalytical high-performance liquid chron.m.r. data for, 139 matography, 34 -, 1,2-O-isopropylidene-a-, 3-deoxy-3-fluoro-, 'Hand I9F-n.m.r. 5,6-carbonate, 'H- and I9F-n.m.r. data for, 116 data for, 99 Gluco-oligosaccharides, a-(I+4)-linked, 'H- and 19F-n.m.r.data for, 99, 139 -, I ,2-O-isopropylidene-3-C-(methox- liquid chromatography analysis, 3840 yally1)-a-, IH- and 19F-n.m.r.data D-GlUCOpyranOSe for, 139 -, 2-acetamido-2,6-dideoxy-6-flu0r0-, 5,6-phenylboronate, IH- and I9Fa anomer, IH- and 19F-n.m.r. data for, n.m.r. data for, 99 121 -, 5-deoxy-5-fluoro-, 1,3,4-tri-O-acetyl-, 'H- and I9Fa anomer, I3C-n.m.r. data for, 166 n.m.r. data for, 121 p anomer, I3C-n.m.r. data for, 166 -, 3-0-acetyl- 1,6-anhydro-2,4-dideoxy-, 1,2-O-isopropylidene-a-, ITn.m.r. data for, 167 P-, 2-acetamido-4-fluoro-, 'H- and I9F-, 6-deoxy-6-fluoron.m.r. data for, 114 -, 3,5-O-benzylidene-1,2-O-isopropy-, 4-acetamido-2-fluoro-, 'H- and I9Flidene-a-, IH-and I9F-n.m.r. data for, 100 n.m.r. data for, 114 2,4-difluoro-P-, 'H- and 19F-n.m.r. data -, 1,2:5,6-di-O-isopropylidene-a-, IHfor, 151 and I9F-n.m.r. data for, 100 -, 1,2:3,5-di-O-methylidene-a-, IH-, 1,6-anhydro-2-deoxy-2-fluoro-pand I9F-n.m.r. data for, 100 -, 3-O-acetyl-4-O-benzyI-,IH- and -, 1,2-O-isopropylidene-a-, IH- and 19F-n.m.r. data for, 114 19F-n.m.r.data for, 100 -, 3,4-di-O-acetyl-, 'H- and I9F-, 1,2-O-isopropylidene-5-O-benzyln.m.r. data for, I14 a-,'H- and 19F-n.m.r.data for, -, 3,4-di-O-benzyl-, 'H- and 19F100 n.m.r. data for, I14 D-Glucofuranosyl fluoride -, 1,5-anhydro-2-deoxy-2-fluoro1-C-, 2,3,5,6-tetra-O-acetylmethyl-a-, 3,4,6-tri-O-acetyl-, 'H13C-n.m.r. data for, 165 and 19F-n.m.r. data for, 113 IH-and I9F-n.m.r. data for, 97 -, 2-deoxy-2-fluoro-, 2,3,5,6-tetra-O-benzoyl-, 'H- and I9Fa anomer n.m.r. data for, 97 I3C-n.m.r. data for, 162 -, 3,5,6-tri-U-acetyl-2-O-rnethyl-, I3C'H-and I9F-n.m.r. data for, 86 n.m.r. data for, 166 p anomer -, 2,5,6-tri-O-acety1-3-O-methyl-, 13C"C-n.m.r. data for, 162 n.m.r. data for, 166 'H- and I9F-n.m.r. data for, 86 (D-Glucofuranosyl fluoride)urono-6,3-, 1,3,4,6-tetra-O-acetyl-, 'H- and lactone I9F-n.m.r. data for, 86 -, 2,5-di-O-acetyl-p-, 'H- and I9F-n.m.r. -, 1,3,4,6-tetra-O-acetyl-a-, 'H-and data for, 116 IgF-n.m.r. data for, 162

370

SUBJECT INDEX

-, 3-deoxy-3-fluoroa anomer 4hu-n.r. data for, 163 'H- and 19F-n.m.r. data for, 90 p anomer Wn.m.r. data for, 163 IH- and I9F-n.m.r. data for, 91 -, 6-phosphate, IH- and 19F-n.m.r. data for, 91 -, 1,2,4,6-tetra-O-acetyl-, 'H-and I9F-n.m.r. data for, 91 -, 4-deoxy-4-fluoroa anomer 13C-n.m.r.data for, 164 IH- and I9F-n.m.r. data for, 93 p anomer W-n.m.r. data for, 164 IH- and I9F-n.m.r. data for, 93 -, 1,2,3,6-tetra-O-acetyl-p-, 'H- and I9F-n.m.r. data for, 93 -, 6-deoxy-6-fluoroa anomer I3C-n.m.r. data for, 164 IH- and 19F-n.m.r. data for, 95 p anomer I3C-n.m.r. data for, 164 IH- and I9F-n.m.r. data for, 95 -, 1,2,3,4-tetra-O-acetyl-, IH- and 19F-n.m.r. data for, 95 L-Glucopyranose -, 2,6-dideoxy-2-fluoroa anomer, IH- and I9F-n.m.r. data for, 132 p anomer, IH- and 19F-n.m.r.data for, 132 -, 1,3,4-tri-O-acetyl-, 'H- and I9Fn.m.r. data for, 133 n-Glucopyranoside -, 2-acetamido-2,6-dideoxy-6-fluoro-a-, benzyl 3,4-di-O-acetyl-, IH- and 19F-n.m.r. data for, 121 -, methyl 3,4-di-O-acetyl-, 'H-and I9F-n.m.r. data for, 121 -, methyl 3,4-di-O-methyl-, IH- and 19F-n.m.r.data for, 121 -, 4,6-O-benzylidene-2,3-dideoxy-3fluoro-u-, benzyl 2-acetamido, 'H- and I9Fn.m.r. data for, 119 -, benzyl 2-azidoW-n.m.r. data for, 171

IH- and I9F-n.m.r. data for, I19 -, benzyl 2-benzamido-, T-n.m.r. data for, 171 -, methyl 2-benzamido-, IH- and I9Fn.m.r. data for, 119 -, 2-deoxy-2-fluoro-, methyl 4,6-di-O-acetyl-3-O-benzylp-, IH- and I9F-n.m.r. data for, 86 -, methyl 3-O-acetyl-4,6-O-benzylidene-p-, IH- and 19F-n.m.r. data for, 87 -, methyl 3-O-benzyl-4,6-O-benzylidene-P-, IH- and I9F-n.m.r. data for, 87 -, methyl 4,6-0-benzylidene-3-0methyl-p-, IH- and 19F-n.m.r. data for, 87 -, phenyl 3,4,6-tri-O-acetyl-p-, IHand I9F-n.m.r. data for, 87 -, trifluoromethyl 3,4,6-tri-O-acetyla-,IH- and I9F-n.m.r. data for, 87 -, 3-deoxy-3-fluoro-, benzyl p-, IH- and 19F-n.m.r. data for, 91 -, benzyl 2,4,6-tri-O-acetyl-p-, 'Hand I9F-n.m.r. data for, 91 -, methyl 2-O-acetyl-4,6-O-benzylidene-p-, IH- and I9F-n.m.r. data for, 91 -, 6-deoxy-6-fluoro-, methyl, 'H- and 19F-n.m.r. data for, 96 -, p-nitrophenyl p-, IH- and 19Fn.m.r. data for, 96 -, phenyl, IH- and I9F-n.m.r. data for, 96 -, methyl 2,3,4-tri-O-benzyl-a-, 'Hand I9F-n.m.r. data for, 96 -, methyl 2-acetamido-3-U-acetyl-2,4,6trideoxy-4,6-difluoro-a-,IH- and I9F-n.m.r. data for, 157 -, methyl 4-azido-4,6-dideoxy-6-fluoroa-,I3C-n.m.r. data for, 171 -, methyl 2-benzamido-2,6-dideoxy-6fluoro-a-, 3-O-benzyl-, IH- and IgF-n.m.r. data for, 122 -, 3-O-benzyl-4-O-mesyl-, IH- and 19F-n.m.r. data for, 122 -, 3,4-di-O-acetyl-, IH- and I9Fn.m.r. data for, 121

SUBJECT INDEX

37 1

-, methyl 2-benzamido-2,4,6-tndeoxy-, 3,4,6-tri-O-acetyl-, IH- and I9F4,6-difluoro-an.m.r. data for, 117 -, 3-O-acetyl-, 'H- and 19F-n.m.r. -, 2-deoxy-2-fluorodata for, 157 Q anomer, 'H- and 19F-n.m.r.data for, -, 3-O-benzyl-, 'H- and 19F-n.m.r. 146 data for, 157 -, 3,4,6-tri-O-acetyl-, IH- and I9F-, p-nitrophenyl 6-deoxy-6-fluoro-, l3Cn.m.r. data for, 146 n.m.r. data for, 165 -, 3-deoxy-3-fluoro-, 2,3,6-tri-O-acetyl-, -, methyl 4-deoxy-4-fluoroIH- and I9F-n.m.r. data for, 148 -, 6-0-acetyl-2,3-di-O-methyl-a-, 'H-, 4-deoxy-4-fluoro-, 2,3,6-tri-O-acetyl-, and I9F-n.m.r. data for, 94 IH- and 19F-n.m.r. data for, 148 Q anomer, 'H- and I9F-n.m.r. data for, -, 6-deoxy-6-fluoro-, 2,3,4-tri-O-acetyl-, 93 IH- and 19F-n.m.r. data for, 148149 -, 2,3-di-O-methyl-a-, IH- and I9F-, 2,3-di-O-acetyl-4,6-0-benzylidene-, n.m.r. data for, 94 -, 2,3,6-tri-O-acetyl-a-, IH- and I9F'H- and 19F-n.m.r. data for, 82 -, 2,3-di-O-benzoy1-4,6-di-O-methyl-, n.m.r. data for, 93 IH- and 19F-n.m.r. data for, 83-, 2,3,6-tri-O-benzoyl-a-, 'H- and 84 I9F-n.m.r. data for, 94 -, methyl 6-deoxy-6-fluoro-, 2,3,4,6-tetra-O-acetyla anomer, 13C-n.m.r.data for, 165 I3C-n.m.r. data for, 160 f3 anomer, 13C-n.m.r.data for, 165 'H- and 19F-n.m.r. data for, 82 -, methyl 3,6-di-O-acetyl-2,4-dideoxy-, 2,3,4,6-tetra-O-benzoyI-, IH- and I9F4-flU01-0-an.m.r. data for, 83 -, 2-acetamido-, 'H- and 19F-n.m.r. -, 2,3,4,6-tetra-O-benzyl-a-, IH- and I9F-n.m.r. data for, 84 data for, 119 -, 2-benzamido-, IH- and 19F-n.m.r. -, 2,3,4,6-tetra-O-methyl-, IH- and I9Fdata for, 119 n.m.r. data for, 84 -, methyl 4,6-dideoxyd-fluoro-a-, 3,4,6-tri-O-acetyl-2-deoxy-, 4-amino-, 'H- and 19F-n.m.r.data -, 2-bromo-, IH- and I9F-n.m.r. data for, 122 for, 129 -, 4-azido-, IH- and 19F-n.m.r. data -, 2-chloro-, 'H- and I9F-n.m.r. data for, 122 for, 129 -, phenyl p-, photoinduced, electron-, 2-iodo-, IH- and I9F-n.m.r. data transfer reaction of, with 1,4-difor, 129-130 cyanonaphthalene, 184-185 -, 3,4,6-tri-O-acetyl-2-0-methyl-, phenyl 6-deoxy-6-fluoroI3C-n.m.r. data for, 160 a anomer, I3C-n.m.r. data for, 165 IH and 19F-n.m.r.data for, 83 p anomer, 13C-n.m.r.data for, 165 -, 2,4,6-tri-O-acetyl-3-0-methyl-, I3CL-Glucopyranoside, trifluoromethyl 3,4-din.m.r. data for, 160 0-acetyl-a-, 'H-and 19F-n.m.r.data -, 3,4,6-tri-O-benzoyl-2-0-methyl-, IHfor, 133 and 19F-n.m.r. data for, 83 D-Glucopyranosyl fluoride -, 2,4,6-tn-O-benzoyl-3-O-methyl-, IHQ anomer and 19F-n.m.r. data for, 83 13C-n.m.r. data for, 160 L-Glucopyranosyl fluoride 'H- and I9F-n.m.r. data for, 82 -, 3,4-di-O-acetyl-2,6-dideoxy-2-fluorof3 anomer a-,IH- and 19F-n.rn.r. data for, 153 13C-n.m.r. data for, 160 'H-and I9F-n.m.r. data for, 82 -, 2,3,4-tri-O-acetyI-6-deoxy-c~-, I3Cn.m.r. data for, 172 -, 2-acetamido-2-deoxy-pp-D-Glucopyranosyl polymer, catalyzed by IH- and 19F-n.m.r. data for, 117

372

SUBJECT INDEX

p-D-galactosyltransferase, incorporation of D-galactose into, 187 Glucosaccharinic acid -, a-D-, formation, 292-293 structure, 291 Glucose liquid chromatography methods for analysis of, 33 liquid chromatography separation, 52-53 D-Glucose alkaline degradation of, 292 with L-asparaghe, pyrazines formed from, 316-317 degradation products of, 296 in food, liquid chromatography separation, 52 formation of S-(hydroxymethyl)-2-furaldehyde from, 284-285 formation of Amadori compounds from, 307-308 heated neutral solutions of, antimicrobial activity formed in, 326 Maillard reaction between glycine and, 309 phenols from, 290, 295 with L-phenylalanine, products obtained from, 317 in plant cell-wall hydrolyzates, liquid chromatography analysis, 55 reaction of with glycine, pyrazines formed, 315316 with methylamine in dilute acetic acid, 3 14 D-Glucose oligosaccharides, a-( 1-4)linked, liquid chromatography analysis, 37-40 Glucosiduronase -, p-, isolation of carbohydrates from, on analytical-scale columns, 60 -, p-D-, oligosaccharides, liquid chromatography separation, 42-43 D-Glucuronic acid, phenols from, 290 Glycans, complex, glycoprotein-derived, reversed-phase chromatography, 4344 Glyceraldehyde, 321 dehydrated to pyruvaldehyde, acidic conditions, 278-279 high-temperature transformation, in alkali conditions, 284

Glycocalicin, sialylated oligosaccharides, fractionation, 46 GIycoconjugates acid hydrolysis of, 265-269 methanolysis, 258-259 neutral and amino monosaccharides of, measurement of, 268 nondialyzable, by hydrochloric acid, 267 Glycolipids, hydrolysis with hydrochloric acid, 266 GIycopeptides N-acylated, liquid chromatography separation, 48 complex, ionic, liquid chromatography, 45-49 liquid chromatography separation, 4748 methylated, liquid chromatography separation, 48 prechromatographic purification of, 20 preparative liquid chromatography, 60 sialylated, liquid chromatography separation, 48 Glycoprotein carbohydrates, compositional analysis of, 56 glycosylation site(@, 47-48 hydrolysis of with hydrochloric acid, 267 with ion-exchange resin in acid form, 268-269 methanolysis, 257 for analysis of carbohydrates in, 258 structure, liquid chromatography analysis, 46-47 Glycosaminoglycans, 7 composition, analysis, 55 isolation of carbohydrates from, on analytical-scale columns, 60 GIycosaminoglycuronans oligosaccharides, liquid chromatography separation, 48 sulfated oligosaccharides, chromatographic separation of, 49 Glycosidases, 270 Glycoside linkages, methanolysis, 259 Glycosides large-scale preparative liquid chromatogw h y , 62

SUBJECT INDEX liquid chromatography, pre-column derivatization procedures, 68 photosensitive protecting groups, 182187 preparative liquid chromatography, 60 Glycosidic linkages, 250 acetolysis, 252, 269-270 with activating group at p-position, cleavage, 255 cleavage, 250-25 1 liberation of N- and 0-linked carbohydrate chains, 255-256 enzymic hydrolysis, 270-271 formolysis, 252, 269-270 hydrolysis correction factors, 254 internal standard, 254 liberation of neutral monosaccharides during, 252-253 recoveries from, 255 methanolysis, 252 deamination prior to, 256 recoveries from, 255 reductive cleavage, 271 synthesis, 250 total hydrolysis with acid, 259-269 Glycosylation sites isolation, 47-48 separation of, 47-48 N-Glycosylic linkage, cleavage, 255 Glycuronans decarboxylation, 306 high-temperature transformation of, 305307 hydrolysis, 265 in marine algae, 307 Guanosine derivatives, diastereoisomeric, 28 Guaran, hydrolysis, 265 Guatambuine, 13 o-Gulopyranoside, benzyl 2-acetamido-3O-acetyl-2,4-dideoxy-4-fluoro-6-0trityl-a-, 'H- and 19F-n.m.r. data for, 119 Gums, hydrolysis of, 263, 265

H Hayashi, H., 7 Hemicellulose, 300 hardwood, 305

373

high-temperature transformation of, 305307 non-fermentable oligosaccharides, liquid chromatography methods for, 52 polysaccharides, 305 softwood, 305 Heparin isolation of carbohydrates from, on large-scale columns, 62 structural and sequence analysis of, 49, 57 sulfated disaccharides, liquid chromatography, 37 Heparin sulfate, composition, analysis, 55

Heptonic acids, D-glyCerO-D-gUlO-, analytical high-performance liquid chromatography, 34 5-Heptylbarbituric acid, cyclodextrin inclusion complexes with, 223, 224 Hexa-O-p-D-glucopyranosyl-D-glucitols isomeric, liquid chromatography separation, 41-42 preparative liquid chromatography, 60 2,4-Hexanedione, formation of, 318 1-Hexanol, cyclodextrin inclusion complexes with, 222-224 D-nrubino-Hex- 1-enitol, 1,2-dideoxy-I , 1-

difluoro-3,4:5,6-di-O-isopropylidene-, IH- and 19F-n.m.r. data for, 159

~-ery?hro-Hex-5-enofuranose,3,5,6-trideoxy-6,6-difluoro-l,2-O-isopropylidene-a']C-n.m.r. data for, 176 'H- and 19F-n.m.r. data for, 154 ~-lyxo-Hex-5-enofuranose,5 ,6-dideoxy-6,6difluoro-1,2-O-isopropylidene-3-0methyl-p-, Y h . m . r . data for, 176 ~-ribo-Hex-5-enofuranose,5 ,6-dideoxy6,ddifluoro- I ,2-O-isopropylidene-Omethyl-a-, lIC-n.m.r. data for, 176 ~-xy~o-Hex-5-enofuranose, 1,2-o-isopropylidene-5,6-dideoxy-6,6-difluoro-3-0methyl-a-, IH- and 19F-n.m.r. data for, 154 ~-ribo-Hex-5-enofuranoside,methyl 5,6dideoxy-6,6-difluoro-2,3-O-isopropylidene-a-

374

SUBJECT I N D E X

IT-n.m.r. data for, 176 -, xylo-, IH- and I9F-n.m.r. data IH- and 19F-n.m.r. data for, 154 for, 141 -, 3-deoxy-3-C-(fluoromethylene)Hex-2(or 3)-enopyranose derivatives, fluorinated, IH- and I9F-n.m.r. data 1,2:5,6)-di-O-isopropylidene-afor, 134 -, ribo-, 'H- and I9F-n.m.r. data ~-erylhro-Hex-2-enopyranoside,2,3,6for, 140 -, xylo-, 'H- and '9F-n.m.r. data trideoxy-6-fluoro-afor, 140 -, ethyl 4-0-acetyl-, IH- and 19F-n.m.r. -, 2-deoxy-2-fluoro-, 'H- and 19F-n.m.r. data for, 134 data for, 99 -, methyl 4-0-acetyl-, IH- and I9F-, 3-deoxy-3-fluoro-, IH- and 19F-n.m.r. n.m.r. data for, 134 data for, 99 ~-threo-Hex-4-enopyranoside,methyl 3benzamido-2,3,4,6-tetradeoxy-2-fluoro- -, 5-deoxy-5-fluoro-, 'H- and 19F-n.m.r. data for, 100 a-,IH-and 19F-n.m.r. data for, -, 6-deoxy-6-fluoro-, IH- and I9F-n.m.r. 127 data for, 100 ~-threo-Hex-4-enopyranoside,methyl 2benzamido-3-0-benzyl-2,4,6-trideoxy- -, D,L-ribo-, 3-acetamid0-2,3,5,6-tetradeoxy-S6-fluoro-p-, 'H- and I9F-n.m.r. data for, 127 fluoro-p-, "C-n.m.r. data for, ~-arabinp-Hex-5-enopyranoside 171 -, methyl 3-benzamido-4-0-benzoyl-, 3-acetamido-2,3,5,6-tetradeoxy;52,3,6-trideoxy-2-fluoro-(~-,I3C-n.m.r. fluoro- 1-044 nitrobenzoy1)-u,pdata for, 171 IH- and 19F-n.m.r.data for, 128 -, 2,3,6-trideoxy-2-fluoro-2-a-, methyl 3-acetamido-2,3,5,6-tetra-, benzyl 3-azido-, 'H- and 19F-n.m.r. deoxy-5-fluoro-p-, IH- and I9Fdata for, 126 n.m.r. data for, 128 -, benzyl 3-benzamido-, IH- and I9F- Hexofuranosides n.rn.r. data for, 127 -, 6-deoxy-6-fluoro-, 'H- and I9F-n.m.r. -, methyl 3-benzamido-, IH- and I9Fdata for, 100 n.m.r. data for, 127 -, 5-deoxy-5-fluoro-, IH- and I9F-n.m.r. -, methyl 3-benzamido-4-0-benzoyl-, data for, 100 'H- and I9F-n.m.r. data for, 127 -, methyl 3-acetamido-2,3,5,6-tetra-, methyl 4-0-benzoyl-3-trifluoroacedeoxy-5-fluoro-~,~-ribotamido-, IH- and I9F-n.m.r. data a anomer, W-n.rn.r. data for, 171 for, 127 p anomer, "C-n.m.r. data for, 128, Hexobarbital, cyclodextrin inclusion com172 plexes with, 223, 224 D-xylo-Hexo-l,4-furanos-5-ulose, S(S)-S-CHexodiulosonic acid, 2,5-D-lhreO-, 34 acetoxy-3,5-0-benzylidene-6-deoxy-6Hexofuranoses fluoro-l,2-O-isopropylidene-ar-, IHDand 19F-n.m.r. data for, 143 -, 1-0-acetyl-2,3,5,6-tetra-O-benzoyl-Hexofuranosyl fluorides 4-deoxy-4-fluoro-p13C-n.m.r.data for, 165-167 'H- and I9F-n.m.r. data for, 97-98 -, galacto-, 'H-and I9F-n.rn.r. data for, 143 Hexop yranose -, gluco-, 'H- and I9F-n.m.r. data -, 6-azido-4-0-benzoyl-2,3,6-trideoxy-2for, 143 fluoro-D-ribo-, 3-deoxy-3-C-(difluoromethylene)(Y anomer, IH- and I9F-n.m.r. data for, 1,2:5,6-di-O-isopropylidene-a126 -, ribo-, 'H- and 19F-n.m.r. data p anomer, 'H- and 19F-n.m.r. data for, for, 141 126

SUBJECT I N D E X -, 2-deoxy-2-fluoro-, 'H- and 19F-n.m.r.

375

-, 2-deoxy-~-/yxodata for, 85-89 -, 3,6-di-O-benzoyl-a-, 'H- and IyF-, 3-deoxy-3-fluoro-, 'H- and 19F-n.m.r. n.m.r. data for, 131 data for, 90-92 -, 4,6-di-O-benzoyl-a-, 'H- and I9F-, 4-deoxy-4-fluoro-, IH- and i9F-n.m.r. n.m.r. data for, 131 data for, 92-94 -, 3,4,6-tri-O-benzoyl-a-, 'H- and -, 6-deoxy-6-fluoro-, IH- and I9F-n.m.r. 19F-n.m.r. data for, 131 data for, 95-96 13C-n.m.r. data for, 160-161 Hexopyranoside derivatives, fluorinated, 'H- and '9F-n.m.r. data for, 82-85 'H- and '9F-n.m.r.data for, 135 Hexosamines, liquid chromatography, preHexopyranosides column derivatization procedures, 68 -, D-riboHexose -, methyl 6-azido-4-O-benzoyl-2,3,6- -, 2-acetamido-2-deoxy-, liquid chrotrideoxy-2-fluoro-p-, IH- and I9Fmatography methods for analysis of, n.m.r. data for, 126 33 -, methyl 4-O-benzoyl-6-bromo-2,3,6- -, D-, 2-acetamido-2-deoxy-, 31 trideoxy-2-fluoro-P-, 'H- and IyF-, 2-deoxy-urubino-, liquid chromatogn.m.r. data for, 135 raphy methods for analysis of, 33 -, methyl 4,5-O-benzylidene-2-deoxy- -, 4-O-(dichloroisoeverninyl)-2,63-C-[(ethoxycarbonyl)- (fluorodideoxy-D-urubino-. See Curacin me thyl)]-(~-~-ribo-hexopyranoside high-temperature transformation ( R ) isomer, "C-n.m.r. data for, 172 acidic conditions, 284-291 ( S ) isomer, I3C-n.m.r. data for, 172 basic conditions, 291-295 -, 2-deoxy-2-fluoro-, 'H- and IyF-n.m.r. saccharinic acids formed from, 291 data for, 85-89 L-nrubino-Hexo- 1 ,5-pyranos-5-ulose, 5(R)-, 3-deoxy-3-fluoro-, 'H- and I9F-n.m.r. 5-C-acetoxy-6-deoxy-6-fluoro-1,2:3,4data for, 90-92 di-0-isopropylidene-(3-,'H- and I9F-, 4-deoxy-4-fluoro-, 'H- and IyF-n.m.r. n.m.r. data for, 142 data for, 92-94 D-lyxo-5-Hexosulopyranuronic acid, in -, 6-deoxy-6-fluoro-, 'H- and iyF-n.m.r. mosses, 323-324 data for, 95-96 1,3,-dideoxy-l-fluoro-3~-xy~o-4-Hexulose, Hexopyranosid-2-dose iodo- 1,2:5,6-di-O-isopropylidene-a-, -, ~-ribo-3-keto,reductic acid forma'H- and I9F-n.m.r. data for, 159 tion from, 289 Hexulosonic acid -, methyl P-D-urubino-, reductic acid -, ~-urubino-2-,analytical high-perforformation from, 289 mance liquid chromatography, 34 D-ribo-Hexo-pyranos-3-ulose hydrate, 1,6-, D-XylO-5-, analytical high-perforanhydro-2,4,-dideoxy-2,4-difluoro-P-, mance liquid chromatography, 34 'H- and 19F-n.m.r. data for, 151 -, ~-xylo-2-,analytical high-perforHexopyranosyl fluorides mance liquid chromatography, 34 -, 2-deoxy-, 'H- and i9F-n.m.r. data Hexuronic acids for, 131-132 decarboxylation, acidic conditions, 288-, 2-deoxy-~-urubino289 -, 3,4,6-tri-O-acetylformation of 2-furaldehyde from, 289 (Y anomer, 'H- and I9F-n.m.r. data ultraviolet-absorbances of, 65 for, 131 5-Hexylbarbituric acid, cyclodextrin inclup anomer, IH- and I9F-n.m.r. data sion complexes with, 223, 224 for, 131 5-Hexyl-2-thiobarbituric acid, cyclodextrin -, 3,4,6-tri-O-benzoyl-a-, 'H- and inclusion complexes with, 223, 224 "F-n.m.r. data for, 131 Heyns rearrangement, 308

376

SUBJECT I N D E X

High-mannose oligosaccharides, sizefractionation of, 62 High-performance affinity chromatography,

18 High-performance liquid chromatography,

17-72 alkylated (reversed-phase) silica gels,

27-30 amine-modified silica gels, 23 aminopropyl-bonded phase columns, maintenance of, 24 aminopropyl-bonded silica gels, for preparative purposes, 59 analytical separation, 32-49 anion-exchange resins and silica gels, 30 automated fraction-collectors, 23 bonded-phase silica cartridges, 19 Cls-bonded silica columns, for preparative purposes, 59 boronic acid substituted silica gel, 31 cartridge-type filtration-units, 20 cation-exchange resin columns, 24-27 applications, 26 calcium-form, 26-27,50-52 hydrogen-form, 25-26,50 lead-form, 26,50-51 maintenance, 27 for preparative purposes, 59 silver-form, 26,50 Cls-bonded silica-gel columns, 28-29 column design, 21 column ovens, 22 column-packing equipment, 21-22 data systems, 22-23 degassing instruments, 19 detectors, 22 diol-modified silica gel, 31 equipment for preserving column-life,

19-20 filters, 20 fittings, 20 guard columns, 19 injectors, 20-21 instrumentation, 18-23 ion-exchange resins, 31 in plastic cartridges, 19 mini-columns, 19-20 phenyl-bonded phase, 28 post-column reaction-modules, 22 pre-columns, 19,27

preparative, solvent-delivery system, 19 refractive-index detectors, 18 reversed-phase columns, 24,29 reversed-phase silica-gel phases, 28 silica saturator columns, 19 solvent-delivery systems, 18-19 stationary phases, 23-31 switching valves, 20 Hirano, S., 4,6,7 Hirase, Susumu, 1, 9 Histocompatability antigens, oligosaccharides, liquid chromatography separation, 43 ‘H-N.m.r. spectroscopy, 59 chemical shifts, 75 geminal coupling, 2J (IH, 19F),75 IH-l9F coupling constants, 75-77 long-range coupling 4J, (IH,I9F),76-77 long-range coupling sJ, (IH, I9F), 76-77 long-range coupling 6J, (IH, I9F),77 structural-reporter-group concept, 79 vicinal coupling, 3J (IH, I9F), 75-76 Houssay, B., 12 Human cerebral-cortex ganglioside, hydrochloric acid hydrolysis, 267 Humus formation, carbohydrate transformation in, 323-326 Hyaluronate oligosaccharides, liquid chromatography separation, 48-49 Hyaluronic acid composition, analysis, 55 structural and sequence analysis of, 57 Hydrazones, as photosensitive protecting groups, 195 Hydrochloric acid hydrolysis of glycoconjugates with, 266 hydrolysis of polysaccharides with, recoveries of monosaccharides after, 260-261 pH of aqueous solutions of, 252 Hydrocinnamic acid, cyclodextrin inclusion complexes with, 222,224 Hydrolysis, for cleavage of glycosidic linkages, 252 Hydroxide ion, cyclodextrin inclusion complexes with, 221 2-Hydroxy-6-(hydroxymethyI)-3(2H,6H)pyranone, 323 3-Hydroxy-6-(hydroxymethyl)-2-methylchromone, 290

SUBJECT I N D E X

377

L-Idofuranose 2-(2-Hydroxyacetyl)furan, 3 18 -, 3,6-anhydro-5-deoxy-5-fluoroformation, 285-287 -, 1,2-di-O-acetyl-, IH- and I9F4-Hydroxybenzoate ion, cyclodextrin n.m.r. data for, 115 inclusion complexes with, 221 -, 1,2-O-isopropylidene-p-, 'H- and 2-Hydroxybenzoic acid, cyclodextrin 19F-n.m.r.data for, 115 inclusion complexes with, 223, 224 -, 3,6-anhydro-5-deoxy-5,6,6-trifluoro3-Hydroxybenzoic acid, cyclodextrin 1,2-O-isopropylidene-pinclusion complexes with, 221 Y-n.m.r. data for, 177 4-H ydroxybenzoic acid, cyclodextrin IH- and 19F-n.m.r. data for, 158 inclusion complexes with, 221, 223, -, 3,6-anhydro-6,6-difluoro-I ,2-0224 I-Hydroxy-2-butanone, formation, 294 isopropylidene-p"C-n.m.r. data for, 175 3-Hydroxy-2-butanone, 321 4-Hydroxy-2-butanone, formation, 294 IH- and I9F-n.m.r. data for, 152 2-Hydroxy-3,5-dimethylcyclopent-2-en1-, 5-deoxy-5-fluoroone, formation, 294 a anomer, %-n.m.r. data for, 167 4-Hydroxy-2,5-dimethyl-3(2H)-furanone, p anomer, I3C-n.m.r. data for, 167 formation, 294, 318 -, I ,2-O-isopropylidene-p-, 13CHydroxyl groups, photosensitive protectn.m.r. data for, 167 ing groups, 180-191 5-deoxy-5-fluoro-1,2-O-isopropylidene2-Hydroxy-5-methylcyclopent-2-en-I-one, p-, IH- and 19F-n.m.r. data for, 100 formation, 294 L-Idofuranosyl fluoride, 2-0-acetyl-3,65-(Hydroxymethyl)-2-furaldehyde,296, anhydro-5-0-benzoyla anomer, IH-and 19F-n.m.r. data for, 318 115 effect on color formation, under sulfatepulping conditions, 325 p anomer, IH- and '9F-n.m.r. data for, formation of, 284-285, 287 115 from Amadori compounds, 319-320 L-Idopyranose, 3-deoxy-3-fluoroa anomer, IH- and I9F-n.m.r. data for, liquid chromatography, 53-54 4-Hydroxy-5-methyl-3(2H)-furanone, 3 18 91 p anomer, IH- and I9F-n.m.r. data for, formation, 290-291, 321 from Amadori compound and its 2,391 enolization, 320 IgD 3-Hydroxy-2-methyl-4H-pyran-4-one, 320isolation of carbohydrates from, on analytical-scale columns, 60 32 1 Hydroxy-L-proline, and D-glucose or Loligosaccharides, liquid chromatography separation, 42-43 rhamnose, high-temperature transformation of, 315 sialylated oligosaccharides, fractionation, 46 I-Hydroxy-2-propanone, 32 1 I-Hydroxy-2-propanone, formation, 293 IgM isolation of carbohydrates from, on analytical-scale columns, 60 oligosaccharides, liquid chromatography I separation, 42-43 Ilex paraguariensis, 13 D-Idofuranose Immunoglobulins -, 3-deoxy-3-fluoroglycopeptides, liquid chromatography a anomer, IH- and I9F-n.m.r. data for, separation, 48 99 hydrolysis with hydrochloric acid, p anomer, IH- and 19F-n.m.r. data for, 99 266

378

SUBJECT I N D E X

Inclusion complexes, 205-206 Indolines, formation of, 317 2-(Indolin-l-yl)- I-phenylpropanoic acid, 317 Inoue, Yoshiyuki, 3 Insulin, I 1 Inulins, hydrolysis, 269 Iodide ion, cyclodextrin inclusion complexes with, 221 Iseki, N., 9 Isomaltol. See 2-Acetyl-3-hydroxyfuran Isomalto-oligosaccharides, preparative liquid chromatography, 60 Isomaltose liquid chromatography methods for analysis of, 33 synthesis of, on light-sensitive, solid support, 184, 186 Isomaltotriose, liquid chromatography separation, 41 2',3'-O-Isopropylideneadenosine5'-phosphate, synthesis of, 203 Isopropylidene-a-D-glucofuranose -, I-0-acetyl-3-0-benzyl-2-deoxy-2fluoro-5,6-0-, IH- and I9F-n.m.r. data for, 99 -, S-deoxy-S-fluoro-I,2-0-, IH- and I9Fn.m.r. data for, 100 2',3'-O-lsopropylideneuridine5'-phosphate, synthesis of, 203 Isovaleraldehyde, formed from L-leucine, 311

K Karasawa, I., 3 Kashimura, N., 6, 7 Keratin fibers, hydrolysis of, with hydrochloric acid, 267 Ketofuranose derivatives, mono- and difluorinated "C-n.m.r. data for, 174 IH- and I9F-n.m.r. data for, 144-145 Ketones, protection of, 195-198 Ketopyranose derivatives, fluorinated, IHand I9F-n.m.r. data for, 144 Ketopyranoses, fluorinated, 13C-n.m.r. data for, 173 Ketose disaccharides, large-scale preparative liquid chromatography, 62

Ketoses, liquid chromatography methods for analysis of, 33 Kitaoka, S.,3-4 Kojibiose, liquid chromatography methods for analysis of, 33 Komano, T., 4, 6, 7

L Lactones fluorinated I3C-n.m.r. data for, 170 IH- and IgF-n.m.r. data for, 116 ultraviolet-absorbances of, 65 Lactose in food, liquid chromatography separation, 52 liquid chromatography methods for analysis of, 33 Lactulose, liquid chromatography methods for analysis of, 33 Laminarabiose, liquid chromatography methods for analysis of, 33 D-Laudanine, 13 Leucrose, liquid chromatography methods for analysis of, 33 Levans, hydrolysis, 269 Levulinic acid, 296 Licopodium sururus, 13 Lignin, source of humus, 323 Lignocellulosic materials fermentation products, 326 polysaccharides in, 306 Lipopolysaccharides, bacterial, methanolysis, 258-259 Liquefaction, 273-274, 323 Liquid chromatography, 17-18 accuracy, 63-64 combined techniques, 69-70, 72 detectability, 63-69 direct-detection methods, 65-66 electrochemical detectors, 65 flame-ionization detectors, 65-66 future trends in, 71-72 mass detectors, 65-66 polarimetric detectors, 66 post-column derivatization methods, 6668 pre-column derivatization methods, 6869

379

SUBJECT INDEX

preparative, 58-63, 71-72 in analytical-scale equipment, 59-61 general aspects of, 58-59 in large-scale equipment, 61-63 sample recovery from columns, 59 refractive index detection, 64-65 stationary phases, 71 triple-pulsed amperometry on platinum or gold electrodes, 65 ultraviolet detectors, 65 Liquid chromatography-mass spectrometry, 69-70 Liquid chromatography-n.m.r. spectrosCOPY,69-70 Lobry de Bruyn-Alberda van Ekenstein transformation, 281 Of D-glUCOSe, 303 Lysosomal-storage disorders, urine in liquid chromatography, 44 sialylated oligosaccharides, liquid chromatography analysis, 45-46 L-Lyxofuranose, I-O-acetyl-2,3,5-tri-Obenzoyl-4-fluoro-a-, W-n.m.r. data for, 172 D-LyXOfUranOSyl fluoride -, 2,3-acetoxonium-5-O-acetyl-p-, IHand I9F-n.m.r. data for, 107 -, 2,3-benzoxonium-5-0-benzoyl-a-, 'H-and 19F-n.m.r. data for, 107 -, 5-O-benzoyl-2,3-benzoxonium-a-, W-n.m.r. data for, 168 -, 2,3,5-tri-O-acetyl-, 'H-and I9Fn.m.r. data for, 107 -, 2,3,5-tri-O-benzoylI3C-n.m.r. data for, 168-169 IH-and I9F-n.m.r. data for, 107 D-Ly XOpyranOSe, 1,3,4-tri-O-acetyl-2deoxy-2-fluoro-a-, 'H- and I9F-n.m.r. data for, 104 D-Lyxopyranoside, trifluoromethyl 3,4-di0-acetyl-p-, IH- and 19F-n.m.r. data for, 104 D-LyXOpy~anOSylfluoride

-, 3,4-di-O-acetyl-2-deoxy-, 2-bromo-, IH-and I9F-n.m.r. data for, 135 -, 2-iodo-, 'Hand I9F-n.m.r. data for, 136 -, 2,3,4-tri-0-acetyl-ar-,'H-and I9Fn.m.r. data for, 102

-, 2,3,4-tri-O-benzoyl-a-, IH-and I9Fn.m.r. data for, 102

M Maillard reaction, 311, 318 chromophoric products, 322 at elevated temperatures, 307 factors affecting, 307 non-nitrogenous products, 3 18-321 products of, 320 inhibition of bacterial growth by, 326 Maltol. See 3-Hydroxy-2-methyl-4H-pyran4-one Malto-oligosaccharides linear, preparative liquid chromatography, 60 liquid chromatography large-scale preparative, 61-63 peak-area analyses, 64 Maltose in food, liquid chromatography separation, 52 liquid chromatography methods for analysis of, 33 6-O-a-Maltotriosylcyclomaltoheptaose, 246 Maltulose, liquid chromatography methods for analysis of, 33 L-Mandelic acid, cyclodextrin inclusion complexes with, 222, 224 Mannitol -, D-, 3,4-O-benzylidene-1,6-dideoxy-1,6difluoro-2,5-O-methylene-, 'Hand I9F-n.m.r. data for, 159 -, 1,6-dideoxy-I,6-difluoro-2,5-0methylene-, 'H-and I9F-n.m.r. data for, 159 -, 1,2,4,5,6-penta-O-acetyl-3-deoxy3-fluoro-, 'Hand I9F-n.m.r. data for, 159 liquid chromatography methods for analysis of, 33 D-Mannofuranosyl fluoride -, 2,3:5,6-di-O-acetoxonium-, 'H- and I9F-n.m.r. data for, 98 -, 2,3:5,6-di-O-benzoxonium-, 'H-and I9F-n.m.r. data for, 98

380

SUBJECT INDEX

p anomer, 'H- and 19F-n.m.r. data for, -, 2,3:5,6-di-O-isopropylidene133 13C-n.m.r. data for, 166 -, I ,3,4-tri-O-acetyl-a-, IH- and I9FIH- and 19F-n.m.r. data for, 98 n.m.r. data for, 133 -, 2,3,5,6-tetra-O-acetylD-Mannopyranose, hydrochloride I3C-n.m.r. data for, 166 -, 2-amino-2,6-dideoxy-6-fluoroIH- and I9F-n.m.r. data for, 98 a anomer, IH- and 19F-n.m.r. data for, -, 2,3,5,6-tetra-0-benzoyl-a-, 'H- and 122 I9F-n.m.l'. data for, 98 p anomer, 'H- and IgF-n.m.r. data for, -, 3,5,6-tri-O-acetyl-2-O-methyI-~-, "C122 n.m.r. data for, 166 D-Mannop yranoside Mannonic acids, analytical high-perfor-, methyl 2-deoxy-2-fluoromance liquid chromatography, 34 -, 3-0-acetyl-4,6-0-benzylidene-p-, D-Mannop yranose 'H- and I9F-n.m.r. data for, 88 -, 2-acetamido-2,6-dideoxy-6-fluoroIH- and I9F-n.m.r. data for, 122 -, 3-0-benzoyl-4,6-0-benzylidene-, 'H- and 19F-n.m.r. data for, 88 -, 1,3,4-tri-O-acetyl-, IH- and I9F-, 3-0-benzyl-4,6-0-benzylidene-p-, n.m.r. data for, 122 'H- and I9F-n.m.r. data for, 88 -, 1,6-anhydro-3-deoxy-3-fluoro-p-, 2,4-di-O-acetyl-, IH- and 19F-, 4,6-O-benzylidene-P-, IH- and 19Fn.m.r. data for, 114 n.m.r. data for, 88 IH-and I9F-n.m.r. data for, 114 -, 4,6-di-O-acetyl-3-0-methyl-p-, IH-, 2-deoxy-2-fluoroand I9F-n.m.r. data for, 88 a anomer -, 3,4,6-tri-O-acetyl-P-, IH- and I9F"C-n.m.r. data for, 162 n.m.r. data for, 88 IH- and I9F-n.m.r. data for, 87 -, methyl 6-deoxy-6-fluorop anomer a anomer, IH- and 19F-n.m.r. data for, I3C-n.m.r. data for, 162 96 IH- and I9F-n.m.r. data for, 87 13C-n.m.r. data for, 165 -, 1,2,4,6-tetra-O-acetyl-a-, IH- and -, 2,3-di-O-methyl-, "C-n.m.r. data I9F-n.m.r. data for, 92 for, 165 -, 1,3,4,6-tetra-O-acetyl-p-, I3C-, 2,3-di-O-methyl-a-, 'H- and I9Fn.m.r. data for, 162 n.m.r. data for, 96 -, 1,3,4,6-tetra-O-acetyl-, IH- and -, 2,3-O-isopropylidene-, "C-n. m.r. data for, 165 19F-n.m.r. data for, 87 -, 1,4,6-tri-O-acetyI-3-O-methyl-, 'H-, 2,3-O-isopropylidene-a-, IH- and and I9F-n.m.r. data for, 87-88 "F-n.m.r. data for, 96 -, trifluoromethyl 3,4,6-tri-O-acetyI-2-, 3-deoxy-3-fluorodeoxy-2-fluoro-p-, IH- and I9Fa anomer n.m.r. data for, 88 IT-n.m.r. data for, 163 L-Mannopyranoside, trifluoromethyl 3,4-diIH- and I9F-n.m.r. data for, 92 O-acetyl-2,6-dideoxy-p-, IH- and I9Fp anomer n.m.r. data for, 133 IT-n.m.r. data for, 163 D-Mannopyranosyl fluoride IH- and I9F-n.m.r. data for, 92 -, 2-O-benzoyl-4,6-di-O-methyl-a-, 'H-, 4-deoxy-4-fluoroand I9F-n.m.r. data for, 85 a anomer, I3C-n.m.r. data for, 164 -, 3-0-benzoyl-4,6-di-0-methyl-p-, IHp anomer, I3C-n.m.r. data for, 164 and 19F-n.m.r. data for, 85 L-Mannopyranose -, 2-deoxy-2-fluoro-, 2,6-dideoxy-2-fluorop anomer, 'H- and I9F-n.m.r. data for, a anomer, 'H- and 19F-n.m.r. data for, 146 133

SUBJECT INDEX -, 3,4,6-tri-O-acetyl-, IH- and I9F-

38 1

liquid chromatography, pre-column derivatization procedures, 68 n.m.r. data for, 147 -, 2,3-di-O-benzoyl-4,6-di-O-methyl-, Methyl (5-acetamido-4,7 8,9-tetra-O-acetyl3,5-dideoxy-2-nonulosyl fluoride)onate 'H- and I9F-n.m.r. data for, 84-85 -, 2,3,4,6-tetra-O-acetyl-, a-D-glyCerO-a-D-gUlUCtO-, 13C-n.m.r. data for, 177 I3C-n.m.r. data for, 161 IH- and 19F-n.m.r. data for, 84 -, a-D-glyCerO-p-D-gUlUCtO-, I3C-n.m.r. data for, 177 -, 2,3,4,6-tetra-O-benzoyl-a-, IH- and I9F-n.m.r. data for, 84 Methyl (methyl 4-deoxy-4-fluoro-a-~-, 3,4,6-tri-O-acety1-2-deoxyglucopyranosid)uronate, IH-and 19Fn.rn.r. data for, 116 -, 2-bromo-, IH- and 19F-n.m.r. data Methylation technique, 214 for, 130 5-Methylbarbituric acid, cyclodextrin -, 2-chloro-, 'H- and 19F-n.m.r.data inclusion complexes with, 223, 224 for, 130 2-Methylbenzofuran-5,6-diol, 290 -, 2-iodo-, IH- and I9F-n.m.r. data 3-Methylbenzoic acid, cyclodextrin inclufor, 130 sion complexes with, 222, 224 -, 2,4,6-tri-O-acetyl-3-U-methyl-a-, I3C2-Methylbenzoquinone, formation, 294 n.m.r. data for, 161 -, 3,4,6-tri-O-acetyl-2-O-methyl-a- 4-Methylbenzoylacetic acid, cyclodextrin inclusion complexes with, 223, 224 I3C-n.m.r. data for, 161 Methyl [benzyl2-(benzyloxycarbonyl) IH- and 19F-n.m.r. data for, 84 amino-2,3,4-trideoxy-5-fluoro-a-~L-Mannopyranosyl fluoride erythro-hex-3-enopyranosid]uronate -, 3,4-di-O-acetyl-2,6-dideoxy-2-fluoroW-n.m.r. data for, 172 p-, 'H- and I9F-n.m.r. data for, 153 IH- and 19F-n.rn.r.data for, 116 -, 2,3,4-tri-O-acetyl-6-deoxy-aMethyl 5-deoxy-5,5-difluoro-~-ribofurano13C-n.m.r. data for, 173 side IH-and I9F-n.m.r. data for, 132 -, 3-O-benzyl-a-, 'H- and I9F-n.m.r. Mannose data for, 156 D-, 2,3-O-isopropylidene-p-, IH-and I9Falkaline degradation of, 292 n.m.r. data for, 156 -, 2,6-di-O-methyl-. See Curamycose Methyl 3-deoxy-3-fluoro-a-~-gulopyranoin plant cell-wall hydrolyzates, liquid side, IH- and 19F-n.m.r. data for, chromatography analysis, 55 91 determination of enantiomeric form, 66 Methyl 2-deoxy-2-fluoro-P-~-ribo-hexopyliquid chromatography, 33, 52-53 ranoside, 4,6-0-benzylidene-3-deoxy-, Marenzi, A.D., 13 Marini-Bettolo, G., 13 IH- and 19F-n.m.r. data for, 132 Methyl 5-deoxy-5-fluoro-~-ribofuranoside Mass spectrometers, 69 -, 2,3-di-O-acetyl-, 'H- and 19F-n.m.r. Masuda, F., 6, 7 data for, 112 Mate, 13, 14 -, 2,3-O-isopropylidene-, 'H- and 19FMatsushima, Y.,9 n.m.r. data for, 112-113 Melanoidin, formation, 307 l-deoxyMelibiose, liquid chromatography methods 2,2'-O-Methylenebis(3-O-benzoyl1-fluoro-L-glycerol),IH- and 19F-n.m.r. for analysis of, 33 data for, 158 Mephrobarbital, cyclodextrin inclusion Z,Z'-O-Methylenebis(1-deoxy-l-fluoro-~complexes with, 223, 224 glycerol), IH-and 19F-n.m.r. data for, Methanesulfonates, photolysis of, 191 158 4-Methoxyphenacyl, photocleavage of, 4-O-Methyl-~-glucuronicacid, 306 201-202 2-C-Methylglyceric acid, 303 N-(p-Methoxypheny1)glycosylamines,

-

3

382

SUBJECT I N D E X

Methyl glycosides, 29 high-performance liquid chromatography of, 256 perbenzoylation of, 256 preparative liquid chromatography, 60 Methylglyoxal, liquid chromatography, 5354 Methyl rnaltosides, large-scale preparative liquid chromatography, 62 3-Methyl-2-(2-oxopropyl)thiophene,formation of, 318 a-Methylphenacyl, photocleavage of, 201202 2-Methyl-2-propano1,cyclodextrin inclusion complexes with, 222, 224 2-Methyl-3-propanoylthiophene, formation of, 318 2-Methylpyrazine, formation of, 317 2-Methyl-3-pyridino1,formation of, 312, 313 6-Methyl-3-pyridin01,3 12 5-Methylpyrrole-2-carboxaldehyde,formation of, 312 Milk, human complex, neutral oligosaccharides, liquid chromatography, 44 oligosaccharides, preparative liquid chromatography, 60 sialylated oligosaccharides, liquid chromatography analysis, 45-46 Misaki, A., 9 Miyazaki, N., 6 Moffatt, J.G., 6 Monosaccharides absolute or relative decomposition of, 259 acid hydrolysis, losses, 259 acyclic, IH- and I9F-n.m.r. data for, 158- 159 branched, I3CC-n.m.r. data for, 172-173 deoxy fluorinated, 13C-n.m.r.data for, 172- I73 fluorinated, n.m.r. spectroscopy of, 73178 fluorinated branched, 'H- and IgF-n.m.r. data for, 142-143 formation of phenolic compounds from, 295 high-performance liquid chromatography, 31

ionic, high-performance liquid chromatography, 33-37 large-scale preparative liquid chromatography, 62 methanolysis, 257-258 neutral, analytical high-performance liquid chromatography, 32-33 partially methylated, structural and sequence analysis of, 57 preparative liquid chromatography, 60 pyruvated, of bacterial origin, studied using methanolysis, 259 structural and sequence analysis of, 57 tri- and tetra-fluorinated I3C-n.m.r. data for, 177 IH-and 19F-n.m.r.data for, 158 Mosses, formation of humus from, 323324 Much hydrolysis, by hydrochloric acid, 266267 isolation of carbohydrates from, on analytical-scale columns, 60 methanolysis, 258 oligosaccharides, liquid chromatography separation, 42-43 sialylated oligosaccharides, fractionation. 46

N Neuraminic acid derivatives, fluorinated, I3C-n.m.r. data for, 177 Neuraminic acids hydrolysis, 254 liquid chromatography, 36-37 Neutral sugars, hydrolysis of, 262-263 Nigerose, liquid chromatography methods for analysis of, 33 Nitroanilides, as protecting groups for carboxylic acids, 202 2-Nitrobenylidene derivatives, photochemical cleavage of, 188 2-Nitrobenzaldehyde, photoinduced oxidation-reduction of, 181 3-Nitrobenzoic acid, cyclodextrin inclusion complexes with, 221 4-Nitrobenzoic acid, cyclodextrin inclusion complexes with, 221

SUBJECT INDEX 2-Nitrobenzyl, photochemical cleavage of, I93 P3-1-(2-Nitrobenzyl)adenosine 5’-triphosphate, 204 2-Nitrobenzylcarbonates, photochemical cleavage of, 190-191 2-Nitrobenzyl esters, photochemical cleavage of, 198 2-Nitrobenzyl ethers, 181-182 photochemical cleavage, 18I - I83 proposed mechanism for, 183 2-Nitrobenzyl glycosides photochemical cleavage of, 183 proposed mechanism for, 183 2-Nitrobenzyl group, for protection of carboxylic acids, 198 2-Nitrobenzylidene derivatives in protection of diols, 188 utilized in syntheses leading to trisaccharides of biological significance, 189 2-Nitrobenzyloxycarbonyl group, photochemical cleavage of, 193 2-Nitrobenzyl phosphoric esters, in nucleotide synthesis, 203 2-Nitrophenol, cyclodextrin inclusion complexes with, 222-224 3-Nitropheno1, cyclodextrin inclusion complexes with, 221 4-Nitrophenol, cyclodextrin inclusion complexes with, 221 3-Nitrophenolate ion, cyclodextrin inclusion complexes with, 221 4-Nitrophenolate ion, cyclodextrin inclusion complexes with, 221, 223, 224 3-Nitrophenyl esters, photosolvolysis of, 203 P3-l-(2-Nitrophenylethyl)adenosine5’triphosphate, 204 (2-Nitrophenyl)ethylenedioxy acetals, 195 removal of, by strong base, proposed mechanism for, 196 (2-Nitropheny1)ethylene glycol, 195 (p-Nitrophenyl)hydrazones, liquid chromatography, pre-column derivatization procedures, 68 3-Nitrophenyloxycarbonyl, 193 6-Nitroveratryl p-D-ghcopyranoside, photochemical cleavage of, 184-185

383

6-Nitroveratrylox ycarbonyl group, photochemical cleavage of, 193 6-Nitroveratryl urethans, photochemical cleavage of, 193 Nuclear magnetic resonance spectroscopy advantages of, 73-74 comparison of relevant parameters of different nuclei, 74 of fluorinated monosaccharides, 74 other nuclei, 80 two-dimensional techniques, 74 Nucleoside antibiotics, diastereoisomeric pyrimidine, 28 Nucleoside derivatives, high-performance liquid chromatography, 28 Nucleosides isomeric 2’-deoxy-C-, 28 synthesis of, 6

0 Ochiai, H., 4 Ocotea puberula, 13 Ocotein, 13 Oligoglycosiduronic acids, liquid chromatography, 40-41 Oligosaccharides N-acetylated or deoxy sugar-containing, 29 acidic, animal-derived, large-scale preparative liquid chromatography, 62 chitin-derived, 29 cleavage of glycosidic linkages, 252 complex determining sequence of glycosyl residues in, 58 preparative liquid chromatography, 60 complex (and cyclic), neutral, liquid chromatography, 41-45 complex, ionic, liquid chromatography, 45-49 containing 2-acetamido-2-deoxyhexose units, ultraviolet-absorbances of, 65 cyclic, liquid chromatography separation, 44-45 gl ycoprotein-derived liquid chromatography, 42-43 structural.and sequence analysis of, 57 glycosaminoglycan-derived, liquid chro-

384

SUBJECT INDEX

matography, pre-column derivatization procedures, 68 from glycosaminoglycans, ultravioletabsorbances of, 65 high-mannose, preparative liquid chromatography, 60 hyaluronic acid-derived, liquid chromatography separation, 48 ionic, of animal origin, preparative liquid chromatography, 60 linear, structural and sequence analysis of, 57 liquid chromatography, peak-area analyses, 64 microbial, preparative liquid chromatography, 60 neutral of animal origin, preparative liquid chromatography, 60,62 structural and sequence analysis of, 57 peralkylated, prechromatographic purification of,20 phosphorylated fractionation, 46 preparative liquid chromatography, 60 plant-derived large-scale preparative liquid chromatography, 62 liquid chromatography, 41 sialic acid-containing large-scale preparative liquid chromatography, 62 preparative liquid chromatography, 60 sialylated liquid chromatography separation, 4546 ultraviolet-absorbances of, 65 simple, ionic, liquid chromatography separation of, 40-41 simple, neutral, liquid chromatography analysis, 37-40 simple and complex, liquid chromatography , pre-column derivatization procedures, 68 starch-derived, 29 sulfated preparative liquid chromatography, 60 uronic acid-containing, large-scale preparative liquid chromatography, 62

synthesis of, combined organic-enzymic approach, 184-187 Olivacine, 13 Ombuin, 13 Onodera, Akifumi, 9 Onodera, Fumi, 9 Onodera, Koji, 9 Onodera, Konoshin accomplishments, 4-5 awards and honors, 8-9 baccalaureate graduation thesis, 3 childhood, 2 climbing in Himalayas, 5 editorial work, 8 family, 1-9 fields of research, 6 founder of Japanese Society of Carbohydrate Research, 9 interest in mountain climbing, 2 investigation of synthetic procedure for nucleosides, 6 W.D. thesis, 3 scientific research, 3-4, 5-8 study of biochemistry, 2-3 as teacher, 5 work for Agricultural Chemical Society, 8 work for Biochemical Society of Japan, 8 work habits, 5 work in Laboratory of Biological Chemistry, 3 Onodera, Mizuyo, 9 Onodera, Yukari, 3, 9 Orosomucoid glycopeptides, liquid chromatography separation, 48 isolation of carbohydrates from, on analytical-scale columns, 60 sialylated oligosaccharides, fractionation, 46 Ovalbumin glycopeptides, liquid chromatography separation, 48 hydrolysis, with trifluoroacetic acid, 268 isolation of carbohydrates from, on analytical-scale columns, 60 oligosaccharides, liquid chromatography separation, 42-43

SUBJECT INDEX

sialylated oligosaccharides, fractionation, 46 Ovarian-cyst glycoproteins, oligosaccharides from, liquid chromatography separation, 42-43, 60 Ovomucoid glycopeptides, liquid chromatography separation, 48 isolation of carbohydrates from on analytical-scale columns, 60 on large-scale columns, 62 oligosaccharides, liquid chromatography separation, 43 sialylated oligosaccharides, fractionation, 46

385

-, 5-deoxy-5-fluoro-o-, 'H- and 19Fn.m.r. data for, 112-1 13 L-threo-Pento-1,4-furanos-4-ulose, 4-0acetyl-5-deoxy-5-fluoro-1,2-0-isopropylidene-3-O-tosyl-P-, 'H- and I9Fn.m.r. data for, 143 Pentofuranosides -, 2-deoxy-2-fluoro-, 'H- and I9F-n.m.r. data for, 109-1 I I -, 3-deoxy-3-fluoro-~-,IH- and I9Fn.m.r. data for, I12 -, 5-deoxy-5-fluoro-~-,'H- and I9Fn.m.r. data for, 112-113 Pentofuranosyl fluorides -, 3,5-di-O-benzoyl-2-bromo-2-deoxy-~-, a-D-urubino-, 'H- and I9F-n.m.r. P data for, 138 -, p-D-Xylo-, 'H- and I9F-n.m.r. data Palatinose, liquid chromatography methods for, I38 'H- and 19F-n.m.r. data for, for analysis of, 33 106- I09 Panose, liquid chromatography separation, Pentopyranose derivatives, fluorinated 41 I3C-n.m.r. data for, 167-168 Pectic acid, oligomers, liquid chromatograC(or 0)-branched, IH- and 19F-n.m.r. phy, 40 Pectin, 306, 326 data for, 141-142 Pentopyranoses acid hydrolysis of, correction factors, 254 -, 2-deoxy-2-fluoro-, 'H- and I9F-n.m.r. galacturonic acid units of, hydrolysis data for, 104-105 losses, 261-262 -, 3-deoxy-3-fluoro-, 'H- and 19F-n.m.r. non-fermentable oligosaccharides, liquid data for, 105-106 -, 4-deoxy-4-fluoro-, IH- and I9F-n.m.r. chromatography methods for, 52 2,4-Pentanedione, for enhancing detectabildata for, 105-106 Pentopyranoside ity of carbohydrates, 67 I-Pentanol, cyclodextrin inclusion com-, 2-deoxy-2-fluoro-, 'H- and 19F-n.m.r. plexes with, 222-224 data for, 104-105 Pentobarbital, cyclodextrin inclusion com-, 3-deoxy-3-fluoro-, IH- and 19F-n.m.r. plexes with, 223, 224 data for, 105-106 D-xylo-Pentodialdo-l,Cfuranose -, 4-deoxy-4-fluoro-, IH- and I9F-n.m.r. -, 3-deoxy-3-fluoro-I ,2-0-isopropylidata for, 105-106 dene-a-, n.m.r. data for, 169 -, methyl 2-amino-2,3,4-trideoxy-3-, 1,2-0-isopropylidene-3-deoxy-3fluoro-threofluoro-a-, IH- and 19F-n.m.r.data -, a - ~ - 'H, and 19F-n.m.r. data for, for, 112 128 Pentofuranose derivatives, fluorinated, I3C-, p-D-, IH- and 19F-n.m.r. data for, n.m.r. data for, 168-169 128 Pentofuranoses L-eryrhro-Pentopyranoside -, 2-deoxy-2-fluoro-, 'H- and I9F-n.m.r. -, methyl 2-deoxy-2,2-difluoro-3,4-0data for, 109-1 11 isopropylidene-p-, IH- and 19F-, 3-deoxy-3-fluoro-~-,'H- and I9Fn.m.r. data for, 156 n.m.r. data for, I12 -, methyl 4-deoxy-4,4-difluoro-2,3-0-

386

SUBJECT INDEX

isopropylidene-p-, IH- and I9Fn.m.r. data for, 156 Pentopyranosyl fluorides

Phenylisocyanates, liquid Chromatography, pre-column derivatization procedures, 68 -, 3,4-di-O-benzoyl-2-deoxy-~-erythro-Phosphoric esters, protection of, 202-203 a anomer, 'Hand I9F-n.m.r. data for, Phosphorus pentaoxide, oxidation and 137 polymerization of sugars with, 6 p anomer, IH-and I9F-n.m.r. data for, Phytolncca dioica, 13 137 Pinus elliotti. See Slash pine IH-and t9F-n.m.r. data for, 101-103 Plant cell-wall materials, hydrolysis, 264 Pentose Plant cell-walls -, 2-deoxy-erythro-, liquid chromatogcomplex, acidic oligosaccharides from, raphy methods for analysis of, 33 fractional liquid chromatography difluorinated, IH-and I9F-n.m.r. data methods, 49 for, 155 liquid chromatography analysis, 52 Pentose dehydration, mechanism of, 275 Plant cell-wall sugars, preparative liquid Pentulose, erythro-2-, liquid chromatograchromatography, 60 phy methods for analysis of, 33 Plant fiber, liquid chromatography analy5-Pentylbarbituric acid, cyclodextrin inclusis, 52 sion complexes with, 223, 224 Plant oligosaccharides, preparative liquid 5-Pentyl-2-thiobarbituric acid, cyclodextrin chromatography, 60 inclusion complexes with, 223, 224 Plant polysaccharides Perbenzoates, liquid chromatography, precomplex, structural and sequence analycolumn derivatization procedures, 68 sis of, 57 Perbenzoylated sugars, prechromatomonosaccharide composition of gas-liquid chromatography analysis, graphic purification of, 20 Per-p-bromobenzoates, liquid chromatogra54 liquid chromatography separations, phy, pre-column derivatization proce54-55 dures, 68 Pogonopus tubulosus, 13 Perchlorate ion, cyclodextrin inclusion Poly(galactur0nic acid) lyases, mode of complexes with, 221 action, analysis of, 54 Perchloric acid, cyclodextrin inclusion complexes with, 222, 224 Polysaccharide-degradingenzymes, mode of action, liquid chromatography Periodate, for enhancing detectability of carbohydrates, 67 analysis, 53-54 Polysaccharide hydrolyzates, isolation of, Pernaphthoates, liquid chromatography, pre-column derivatization procedures, on large-scale columns, 62 68 Poly saccharides 1-Phenethylindoline, 3 17 complex, determining sequence of glycoPhenobarbital, cyclodextrin inclusion syl residues in, 58 complexes with, 223, 224 glycosidic linkages, cleavages of, 251Phenol, cyclodextrin inclusion complexes 272 with, 222-224 high-temperature transformation of, 295Phenolics 307 from carbohydrates, 323 mono- and di-saccharides enzymically formation of, 326 released from, structural and seL-Phenylalanine, cyclodextrin inclusion quence analysis of, 57 complexes with, 222, 224 reductive-cleavage, 27 1 Phenyl glycosides, cleavage, photosensiPolysaccharide side-chains, structural and tized by 1,4-dicyanonaphthalene, 184 sequence analysis of, 57 3-Phenylindoline, 3 17 Polyuronic acids, hydrolysis of, 263

SUBJECT INDEX Propanoic acid, cyclodextrin inclusion complexes with, 221 2-Propanol, cyclodextrin inclusion complexes with, 222, 224 5-Propyl-2-thiobarbituric acid, cyclodextrin inclusion complexes with, 223, 224 Protecting groups light-sensitive, 180 modifier, 180 photochemical removal of, 179-180 photosensitive, application to biological models, 203-204 Proteodermatan sulfate, hydrolysis, with trifluoroacetic acid, 268 Pseudocellobiouronic acid, hydrolysis of, 299 Pseudocidamine, racemic, 13 Pseudocorydine, 13 Psicose -, D-, alkaline degradation of, 292 liquid chromatography methods for analysis of, 33 Pyranoses -, 2(or 3)-deoxy-2(or 3)-fluorohexo-, I3C-n.m.r. data for, 161-163 -, 4(or 6)-deoxy-4(or 6)-fluorohexo-, I3C-n.m.r. data for, 163-165 Pyranosides -, 2(or 3)-deoxy-2(or 3)-fluorohexo-, 13C-n.m.r. data for, 161-163 -, 4(or 6)-deoxy-4(or 6)-fluorohexo-, W-n.m.r. data for, 163-165 Pyrazine alkylated, formation of, 315 formation, pathways of, 317 Pyridine, cyclodextrin inclusion complexes with, 222, 224 Pyrocatechol, 290 Pyrogallol, 290 Pyrolysis, 273-274 Pyruvaldehyde, 321 formation, 293 R

Reducing sugars, 214 Reductic acid effect on color formation, under sulfatepulping conditions, 325 formation of, 288

387

as product after acid exposure of Dxylose, 276 Reichstein, T., 13 Rhamnogalacturonan 11, oligosaccharides, liquid chromatography fractionation, 49 Rhamnose determination of enantiomeric form, 66 liquid chromatography methods for analysis of, 33 liquid chromatography separation, 53 L-Rhamnose and ethylamine, reaction between, 313 in plant cell-wall hydrolyzates, liquid chromatography analysis, 55 Ribitol, liquid chromatography methods for analysis of, 33 D-Ribofuranose -, 1-O-acetyl-5-O-(methoxymethyl)-a-, IH- and I9F-n.m.r. data for, 111 -, I-0-acetyl-2-deoxy-2-fluoro-5-0(methoxymethy1)-a-, 13C-n.m.r.data for, 169 -, I-0-acetyl-2,3,5-tri-O-benzoyl-4&oxy-4-fluoro-p-, 13C-n.m.r. data for, 172 -, 5-deoxy-5-fluoro-, IH-and I9F-n.m.r. data for, 112 D-Ribofuranosyl fluoride -, 2,3-acetoxonium-5-O-acetyl-p-, Wn.m.r. data for, 169 -, 2-O-acetyl-3,5-di-O-benzoyl-p-, IHand I9F-n.m.r. data for, 108 -, 3-O-acetyl-2,5-di-O-benzoyl-p-, IHand 19F-n.m.r.data for, 108 -, 5-0-acetyl-2,3-di-O-benzoyI-p-, 'Hand 19F-n.m.r. data for, 108 -, 2,3,5-tri-O-acetyl-, IH-and I9Fn.m.r. data for, 107 -, 2,3,5-tri-O-benzoylI3C-n.m.r. data for, 169 'H- and I9F-n.m.r. data for, 108 Ribonic acids, analytical high-performance liquid chromatography, 34 D-Ribop yranose -, 2-deoxy-2-fluoroa$-, 'Hand 19F-n.m.r.data for, 104 -, 1,3,4-tri-O-acetyl-, IH- and I9Fn.m.r. data for, 104 -, 1,3,4-tri-O-acetyl-2-deoxy-2-fluoro-

388

SUBJECT I N D E X

Slime-mold gl ycoprotein, oligosaccharides, liquid chromatography separation, 4243 Ribonuclease B, glycopeptides, liquid Sodium perchlorate, cyclodextrin inclusion chromatography separation, 48 complexes with, 222, 224 Ribonucleic acid ligase, bacteriophage T4Solanum glaucophyllum, 14 induced, Escherichia coli, 182 Sophorose, liquid chromatography methRibo-oligonucleotides, synthesis of, 181 ods for analysis of, 33 D-Ribopyranosyl fluoride -, 3,4-di-O-acetyl-2-deoxy-2-bromo-, Sorbopyranose -, DIH- and 19F-n.m.r.data for, 136 -, 4-deoxy-4-fluoro-a-, I3C-n.m .r. -, 3,4-di-O-acetyl-2-deoxy-2-fluoro-a-, data for, 173 'H- and I9F-n.m.r. data for, 155 -, 4-deoxy-4-fluoro-1,2-O-isopropyli-, 2,3,4-tri-O-acetyl-, 'H- and I9Fand I9F-n.m.r. data dene-p-, 'Hn.m.r. data for, 102 for, 144 -, 2,3,4-tri-O-acetyl-2-Buoro-p-, IH-, L-, 5-deoxy-S-fluoro-a-, W-n.m.r. and I9F-n.m.r. data for, 143 data for, 173 -, 2,3,4-tri-O-benzoyl-, IH- and I9FSorbose, liquid chromatography methods n.m.r. data for, 102 for analysis of, 33 D-Ribose, 1,3,4-tri-O-benzoyl-p-, 'H- and Sordelli, A., 11 IgF-n.m.r. data for, 104 Starch, 295 S acid hydrolysis of, 296 screw model of, 215 Saccharides Stoppani, A.O.M., 13 from glycoproteins, liquid chromatograStrecker degradation, 311-312, 315, 317 phy separation, 56-57 Streptomyces curacoi, 14 monomeric, high-temperature transforN-Substituted aldosylamine mation of, 275-295 conversion, into l-amino-l-deoxy-2acidic conditions, 275-280 ketose, 308-309 basic conditions, 281-284 formation of, 308 Saccharinic acid, formation, 281-282, 291 Sucrose Saeman hydrolysis, 263-264 in food, liquid chromatography separaSalivary glycoproteins, hydrolysis, with tion, 52 trifluoroacetic acid, 268 liquefaction, 294 Saurine, 13 phenols from, 295 Sauroxine, 13 Sucrose derivatives, 0-methylated, largeSchardinger dextrins. See Cyclodextrins scale preparative liquid chromatograSchima liukiuensis, 3 phy, 62 Sialic acids Sugar acids, fluorinated high-performance liquid chromatogra'lC-n.m.r. data for, 170 'H- and '9F-n.m.r. data for, 116 phy, 31 hydrolysis, 254, 270 Sugar anomers, separation of, 70 liquid chromatography, pre-column Sugar nucleotides, conformations of, 7 derivatization procedures, 68 Sugar phosphates, liquid chromatography separation of, 36 methanolysis, 254 ultraviolet-absorbances of, 65 Sugars determination of enantiomeric form, 66 Sialyllactose, methanolysis, 258 Simple sugars, liquid chromatography, premutarotation rates of, determination, 71 column derivatization procedures, 68 Slash pine, hemicellulose fraction of, 306 pyranose anomers, separation, 70-71 a anomer, '3C-n.m.r. data for, 167

p anomer, 13C-n.m.r.data for, 168

SUBJECT INDEX Sulfite pulping, color-stopping reaction in, 324-325 Sulfuric acid hydrolysis of glycoconjugates with, 266 hydrolysis of polysaccharides with, monosaccharide recoveries after, 259-260 pH of aqueous solutions of, 252 Suzuki, Bunsuke, 2-3

T D-Tagatopyranose, 4-deoxy-4-fluoro-1,2-0isopropylidene-p-, I3C-n.m.r. data for, 173 Tagatose, liquid chromatography methods for analysis of, 33 D-Talofuranosyl fluoride, 2,3,5,6-tetra-Obenzoyl-a-, 'Hand 19F-n.m.r. data for, 98 D-Tdopyranose -, 2-deoxy-2-fluoroa anomer, 'H- and 19F-n.m.r.data for, 88-89 p anomer, 'H-and I9F-n.m.r. data for, 89 D-Talopyranoside -, 2-deoxy-2-fluoro-, trifluoromethyl 3,4,6-tri-O-acetyl-P-, IH-and I9Fn.m.r. data for, 89 -, methyl 4-deoxy-4-fluoro-a"C-n.m.r. data for, 164 'H- and 19F-n.m.r. data for, 94 -, 6-O-trityl-a-, IH- and I9F-n.m.r. data for, 94 -, methyl 4,6-dideoxy-4,6-dilluoro-aW-n.m.r. data for, 175 'Hand 19F-n.m.r. data for, I50 -, 2,3-0-isopropylidene-a-, 'H- and 19F-n.m.r. data for, 150 -, methyl 4,6-dideoxy-4-fluoro-a-, 6-amino-, 'H-and I9F-n.m.r. data for, 120 -, 6-azido-, IH- and 19F-n.m.r. data for, 119 D-Talopyranosyl fluoride -, 2,3,4,6-tetra-O-acetyl-a-, W-n.m.r. data for, 161

-, 3,4,6-tri-O-acetyl-2-deoxy-

389

-, 2-bromo-a-, IH-and 19F-n.m.r. data for, 130 -, 2-iodo-a-, 'H-and I9F-n.m.r. data for, 130 -, 3,4,6-tri-O-acetyl-2-deoxy-2-fluoro-p, 'H- and 19F-n.m.r. data for, 147 1,3,4,6-Tetra-O-acetyl-~-fructofuranosyl fluoride a anomer I3C-n.m.r. data for, 174 IH- and I9F-n.m.r. data for, 144 p anomer T-n.m.r. data for, 174 IH- and 19F-n.m.r. data for, 144 2,3,6,7-Tetrahydro-7-methylcyclopent[b]azepin-8(lti)-one, 3 15 2,3,2',3'-Tetramethoxybenzoin,photocyclization of, 201 Tetrazolium Blue, for enhancing detectability of carbohydrates, 67 Thin-layer chromatography, 28 Thioacetals, as photosensitive protecting groups, 195 Thiocyanate ion, cyclodextrin inclusion complexes with, 221 Thiopental, cyclodextrin inclusion complexes with, 223, 224 Thiophenes, formation of, 318 Thiophenobarbital, cyclodextrin inclusion complexes with, 223, 224 Thyroglobulin, sialylated oligosaccharides, fractionation, 46 p-Toluenesulfonates, photolysis of, 191 Trehaiose, liquid chromatography methods for analysis of, 33 Trifluoroacetic acid hydrolysis of glycoconjugates with, 267268 hydrolysis of polysaccharides with, monosaccharide recoveries after, 261-263 pH of aqueous solutions of, 252 Trimethylacetic acid, cyclodextrin inclusion complexes with, 221 2,3,5-Trimethylbenzoquinone,formation, 294 3,4,5-Trimethylphenyl acetate, cyclodextrin inclusion complexes with, 223, 224

390

SUBJECT I N D E X

Triose-reductone, formation, 294 L-Tryptophan, cyclodextrin inclusion complexes with, 222, 224 Tubulosine, 13 Tumor-cell antigens, glycopeptides, liquid chromatography separation, 48 Tumor-cell glycoproteins, sialylated oligosaccharides, fractionation, 46 Tumor cells, oligosaccharides, liquid chromatography separation, 42-43 Turanose, liquid chromatography methods for analysis of, 33 L-Tyrosine, cyclodextrin inclusion complexes with, 222, 224

-, (4-O-methyl)-~-glucurono)-,model compounds related to, alkaline degradation, 306 Xylanases, mode of action, analysis of, 54 Xylans liquid chromatography analysis, 39 oligosaccharides, 305 wood, alkaline-degradation products of, 305 Xylitol, liquid chromatography methods for analysis of, 33 Xylobiose, liquid chromatography methods for analysis of, 33 D-Xylofuranose -, 3-C-(acetoxymethyl)-3-deoxy-3U fluoro-, 5-0-acetyl- 1,2-O-isopropylideneUmezawa, S., 9 a-,IH- and IgF-n.m.r. data for, Urethans, protection as, 192-194 142 Urinary glycoconjugates, hydrolysis, 262 -, 1,2,5-tri-O-acetyl-, 'H- and I9FUronic acid n.m.r. data for, 142 acid decomposition, 252 -, 3-O-benzyI-5-deoxy-5-fluoro-1,2-Oliquid chromatography isopropylidene-a-, 'H- and 19Fanalytical, 33-34 n.m.r. data for, 113 large-scale preparative, 62 -, 3-deoxy-3-fluoro- 1,2-O-isopropylipre-column derivatization procedures, dene-a68 -, 3-C-(ethoxyallyl)-, 'H- and I9Fmethanolysis of, 257-258 n.m.r. data for, 142 -, 3-C-(hydroxymethyl)-, 'H- and V I9F-n.m.r. data for, 142 -, 3,5-dideoxy-3,5-difluoro-l,2-0Virus glycoproteins isopropylidene-a-, IH-and lyFglycopeptides, liquid chromatography n.m.r. data for, 156 separation, 48 -, 1,2-O-isopropylidene-3-deoxy-3isolation of, on analytical-scale columns, fluoro-5-O-p-tolylsulfonyl-a60 'H- and lyF-n.m.r. data for, 112 D-Xylofuranoside W -, methyl 3-O-benzoyl-5-O-benzyl-2deoxy-2-fluoro-p-, 'H- and 19FWieland, H., 12 n.m.r. data for, 11 I Wolfrom, M.L., 4 -, methyl 2,5-di-O-benzoyl-3-deoxy-3Wood pulps, liquid chromatography analyfluoro-a-, 'H- and I9F-n.m.r. data sis, 52 for, 112 Woody materials, hydrolysis of, 263-264 D-Xylofuranosyl fluoride X -, 3,5-acetoxonium-2-0-methyl-p-, IHand 19F-n.m.r. data for, 109 Xanthates, photochemical cleavage of, 190 -, 3,5-benzoxonium-2-O-methyl-p-, 'HD-Xyh and I9F-n.m.r. data for, 109 -, ~-arabino-(4-O-methyl-~-glucurono)-, -, 3,5-di-O-benzoyl-2-O-methyl-, 'H306 and I9F-n.m.r. data for, 109

391

SUBJECT I N D E X

-, 2,3,5-tri-O-acetyl-, IH- and I9Fn.m.r. data for, 108 -, 2,3,5-tri-O-benzoyl-a-, I3C-n.rn.r. data for, 169 -, 2,3,5-tri-O-benzoyl-P-, IH- and I9Fn.m.r. data for, 109 Xyloisosaccharinic acid, 305 Xylo-oligosaccharides, preparative liquid chromatography, 60 D-Xylopyranose, 1,3,4-tri-O-acetyl-2deoxy-2-fluoro-aI3C-n.m.r. data for, 167, 168 'H- and I9F-n.m.r. data for, 104 D-Xylopyranoside -, benzyl 3-deoxy-3-fluoro-P-, IH- and I9F-n.m.r. data for, 106 -, trifluoromethyl 3,4-di-O-acetyl-a-, IH- and I9F-n.m.r. data for, 105 2-O-~-Xylopyranosyl-~-arabinose, 305 D-Xylopyranosyl fluoride -, 2-deoxy-2-fluoro-, P anomer, 'H-and 19F-n.m.r. data for, 155 -, 3,4-di-O-acetyl-2-deoxy-, 2-bromo-, 'H- and I9F-n.m.r. data for, 136 -, 2-iodo-, IH- and 19F-n.m.r.data for, 137 -, 2,3,4-tri-O-acetyl-, IH- and I9Fn.m.r. data for, 102-103 -, 2,3,4-tri-O-benzoyI-, IH- and I9Fn.m.r. data for, 103

-, 3,4-di-O-acetyl-2-deoxy-2-fluoro-a-, 'H- and 19F-n.m.r.data for, 155

-, 2,4-di-O-acetyl-3-deoxy-3-fluoro-p-,

'H-and I9F-n.m.r. data for, 155 -, 3,4-di-O-benzoyl-2-O-methyl-, 'Hand 19F-n.m.r. data for, 103 -, 2,3,4-tri-O-acetyla anomer, I3C-n.m.r. data for, 167 p anomer, l3C-n.m.r. data for, 167 Xylose, liquid chromatography, 33, 52-53 D-Xylose formation of a- and P-xylometasaccharinic acids from, in base, 281282 formation of 2-furaldehyde from, 275276 formation of saccharinic acids from, 281-282 high-temperature transformation acidic conditions, 276-277 basic conditions, 281-283 in plant cell-wall hydrolyzates, liquid chromatography analysis, 55 Y Yajima, T., 6 Yamada, Yukari, 3 Yamakawa, T., 9 Yoshimura, Juji, 1, 9 Yoshizawa, Z., 9

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