Trends i Synthetic Carbohydrate Chemistry In Trends in Synthetic Carbohydrate Chemistry; Horton, D., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1989. In Trends in Synthetic Carbohydrate Chemistry; Horton, D., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1989. ACS SYMPOSIUM SERIES 386 Trends in Synthetic Carbohydrate Chemistry Derek Horton, EDITOR The Ohio State University Lyn , Eisai Research Institute of Boston, Inc. Glenn J. McGarvey, EDITOR University of Virginia Developed from symposia sponsored by the Divisions of Organic Chemistry and of Carbohydrate Chemistry at the 191st National Meeting of the American Chemical Society, New York, New York, April 13-18, 1986, and the 194th National Meeting of the American Chemical Society, New Orleans, Louisiana, August 30-September 4, 1987 American Chemical Society, Washington, DC 1989 In Trends in Synthetic Carbohydrate Chemistry; Horton, D., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1989. Library of Congress Cataloging-in-Publication Data Trends in synthetic carbohydrate chemistry. Derek Horton, Lynn D. Hawkins, Glenn J. McGarvey, editors. p. cm.—(ACS Symposium Series, 0097-6156; 386). "Developed from a symposium sponsored by the Divisions of Organic Chemistry and of Carbohydrate Chemistry at the 191st National Meeting of the American Chemical Society, New York, New York, April 13-18, 1986, and the 194th National Meeting of the American Chemical Society, New Orleans, Louisiana, August 30-September 4, 1987." Includes bibliographies an ISBN 0-8412-1563-4 1. Carbohydrates—Congresses. I. Horton, Derek, 1932- . II. Hawkins, Lynn D., 1954- . III. McGarvey, Glenn J., 1951- . IV. American Chemical Society. Division of Organic Chemistry. V. American Chemical Society. Division of Carbohydrate Chemistry. VI. American Chemical Society. Meeting (191st: 1986: New York. N.Y.). VII. American Chemical Society. Meeting (194th: 1987: New Orleans, La.) VIII. Series. QD320.T74 1989 547.7'8—dc19 88-39237 CIP Copyright © 1989 American Chemical Society All Rights Reserved. The appearance of the code at the bottom of the first page of each chapter in this volume indicates the copyright owner's consent that reprographic copies of the chapter may be made for personal or internal use or for the personal or internal use of specific clients. This consent is given on the condition, however, that the copier pay the stated per-copy fee through the Copyright Clearance Center, Inc., 27 Congress Street, Salem, MA 01970, for copying beyond that permitted by Sections 107 or 108 of the U.S. Copyright Law. This consent does not extend to copying or transmission by any means—graphic or electronic—for any other purpose, such as for general distribution, for advertising or promotional purposes, tor creating a new collective work, for resale, or for information storage and retrieval systems. The copying fee for each chapter is indicated in the code at the bottom of the first page of the chapter. The citation of trade names and/or names of manufacturers in this publication is not to be construed as an endorsement or as approval by ACS of the commercial products or services referenced herein; nor should the mere reference herein to any drawing, specification, chemical process, or other data be regarded as a license or as a conveyance of any right or permission to the holder, reader, or any other person or corporation, to manufacture, reproduce, use, or sell any patented invention or copyrighted work that may in any way be related thereto. Registered names, trademarks, etc., used in this publication, even without specific indication thereof, are not to be considered unprotected by law. PRINTED IN THE UNITED STATES OF AMERICA In Trends in Synthetic Carbohydrate Chemistry; Horton, D., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1989. ACS Symposium Series M. Joan Comstock, Series Editor 1988 ACS Books Advisory Board Paul S. Anderson Vincent D. McGinniss Merck Sharp & Dohme Research Battelle Columbus Laboratories Laboratories Quin Harvey W. Blanch University of Iowa University of California—Berkeley Malcolm H. Chisholm James C. Randall Indiana University Exxon Chemical Company Alan Elzerman E. Reichmanis Clemson University AT&T Bell Laboratories John W. Finley C. M. Roland Nabisco Brands, Inc. U.S. Naval Research Laboratory Natalie Foster Lehigh University W. D. Shults Oak Ridge National Laboratory Marye Anne Fox The University of Texas—Austin Geoffrey K. Smith Rohm & Haas Co. Roland F. Hirsch U.S. Department of Energy Douglas B. Walters National Institute of G. Wayne Ivie Environmental Health USDA, Agricultural Research Service Michael R. Ladisch Wendy A. Warr Purdue University Imperial Chemical Industries In Trends in Synthetic Carbohydrate Chemistry; Horton, D., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1989. Foreword The ACS SYMPOSIUM SERIES was founded in 1974 to provide a medium for publishin format of the Serie IN CHEMISTRY SERIES except that, in order to save time, the papers are not typeset but are reproduced as they are submitted by the authors in camera-ready form. Papers are reviewed under the supervision of the Editors with the assistance of the Series Advisory Board and are selected to maintain the integrity of the symposia; however, verbatim reproductions of previously pub­ lished papers are not accepted. Both reviews and reports of research are acceptable, because symposia may embrace both types of presentation. In Trends in Synthetic Carbohydrate Chemistry; Horton, D., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1989. Preface CARBOHYDRATES, CHIRAL ORGANIC MOLECULES found naturally or obtained by synthetic transformations, currently comprise a quarter of a million or so known compounds. The rich structural diversity of this group and the multifaceted importance of carbohydrates in biochemistry, medicinal chemistry, microbiology, technology, and many other areas have long challenged synthetic chemists toward a multitude of objectives. The potential of sugars as starting points for highly efficient, stereochemically designed syntheses of noncarbohydrate targets is now increasingly recognize hydrates also serve as excellen stereochemical influence and control of chemical transformations in multifunctional, three-dimensional matrices. Trends in Synthetic Carbohydrate Chemistry is divided into two sections, each of which may be further subdivided into three themes. The first section, "Synthetic Transformations in Carbohydrate Chemistry", surveys a variety of synthetic methodologies useful for transformation of natural saccharides into desired target molecules. The initial three chapters focus on functional-group transformations and protective-group strategy, with special emphasis on aminodeoxy, deoxyfluoro, and deoxynitro sugars and cyclitols, as well as the formation and cleavage of cyclic acetals. Examples of applications to specific synthetic aims are given in Chapters 4-6, including the synthesis of bicyclic nucleosides, the Wittig approach to long-chain sugars, and the transformation of sugar precursors into chiral pyrrolidine alkaloids. The last three chapters of the first section address the ever-significant problem of high-yielding, stereoselective glycosidic coupling procedures, first from the standpoint of basic methodology, next in glycosylations directed toward antibiotics containing deoxy sugars, and finally in the notable applications that have provided practical syntheses of cyclodextrins and complex oligo­ saccharides. The second section of the book, entitled "Total Synthesis of Carbohydrates", focuses on strategies for the generation of monomeric carbohydrates, with major emphasis on the use of nonchiral, acyclic precursors. The contributors do not "reinvent the wheel" by providing tedious synthetic access to abundant natural sugars. Rather, they show xi In Trends in Synthetic Carbohydrate Chemistry; Horton, D., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1989. the potential of synthetic design for controlled access to molecules containing multiple chiral centers that are not readily accessible from natural precursors. Chapters 10-13 illustrate from a variety of viewpoints the great utility of Diels-Alder reactions for the direct and indirect formation of chirally functionalized tetrahydropyrans and tetrahydrofurans. Chapters 14-16 address the aldol reaction and its control, the use of boron and tin enolates, and the use of chiral auxiliaries in the stereocontrolled formation of carbon-carbon bonds generating new chiral centers. Finally, the last two chapters describe the harnessing of enzymes as synthetic tools for chiral precursors and target products, both by use of isolated enzymes and by reactions brought about by living cultures of microorganisms. Trends in Synthetic Carbohydrate Chemistry offers the reader a wealth of contemporary ideas for the construction of complex natural molecules and their analogs, from conceptualization to practical realization. The rich legacy of the carbohydrate literature in conjunction with newer concepts in general organi provides some of the most exciting challenges for today's chemist. As the molecular basis of biological concepts opens up new vistas of understanding, the synthetic chemist is presented with unique opportunities for exercising creative talent toward significant objectives of ever-increasing complexity. Emulation of the virtuosity of nature in synthesis provides an ever-present challenge for the chemist. We hope that the efforts of those who have created this book will bring broader awareness of the role of carbohydrates in modern synthetic work and stimulate others in the pursuit of great intellectual satisfaction and worthy objectives for their creative efforts in the laboratory. This book is an international collaborative effort, with authors from Canada, France, the Federal Republic of Germany, Great Britain, Italy, Japan, Sweden, Switzerland, and the United States. It is not possible to cover all aspects of this subject in a single volume, but the contributions here are broadly representative of innovative work in the field. The order of the chapters is developed from the relationship of the topics and is not necessarily related to the sequence of contributions at the two symposia from which much of the initial material was derived. Acknowledgments The editors deeply appreciate the excellent work of the contributing authors that has made this book possible. We also thank the many other colleagues in the field who have given of their time to review the chapters and offer constructive criticism. Excellent support by the American Chemical Society Divisions of Carbohydrate Chemistry and xii In Trends in Synthetic Carbohydrate Chemistry; Horton, D., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1989. Organic Chemistry helped to make possible the original ACS symposia that provided the impetus for this book. Additional support for the symposia came from Burroughs Wellcome Company, Ciba-Geigy, ICI Americas, The Upjohn Company, Merck & Company, Sandoz Research Institute, SmithKline Beckman, Syntex Research, and Warner Lambert Company. The support and patience of Joan Comstock and Robin Giroux of the ACS Books Department is recognized. We particularly appreciate the fine support and consultation of David C. Baker at all stages of the development of this book. DEREK HORTON Department of Chemistry The Ohio State University Columbus, OH 43210 LYNN D. HAWKINS Eisai Research Institute of Boston, Inc. Lexington, MA 02173 September 3, 1988 xiii In Trends in Synthetic Carbohydrate Chemistry; Horton, D., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1989. Chapter 1 New Synthetic Methods Emphasizing Deoxyfluoro Sugars and Protective-Group Strategy Walter A. Szarek Department of Chemistry, Queen's University, Kingston, Ontario K7L 3N6, Canada The selective introduction of fluorine is of continuing interest not onl but also becaus change in biological activity. The fluoride-ion dis­ placement of carbohydrate trifluoromethanesulfonates using tris(dimethylamino)sulfonium difluorotrimethylsilicate (TASF) provides a convenient route to deoxyfluoro sugars. Partially protected mono­ saccharides, having the anomeric hydroxyl underiva­ tized, react with pyridinium poly(hydrogen fluoride) to yield the corresponding glycosyl fluorides. Two new developments in protective-group strategy are also described. These are (i) a method for the selective silylation of primary hydroxyl groups in carbohydrates involving the use of N-trimethylsilyl- or N-tert- butyldimethylsilyl-phthalimide and (ii) a method for acetal cleavage in carbohydrate derivatives using the simple reagent system, iodine in methanol. The search for new methods of synthesis of halogenated carbohydrates continues to be an active area of investigation. The compounds are of utility as synthetic intermediates, and many of them are of intrinsic value in biochemistry and pharmacology. In the present Chapter methods for the synthesis of deoxyfluoro sugars and glycosyl fluorides are discussed. Because of the polyfunctional nature of carbohydrates, protective-group strategy plays an important role in synthetic methodology involving this class of compounds. In the present Chapter, results are described from a study of the utility of N- trimethylsilyl- and N-tert-butyldimethylsilyl-phthalimide for the selective silylation of primary hydroxyl groups in carbohydrates. Also described, is a new, facile method for cleavage of acetals and dithioacetals in carbohydrate derivatives; the method involves treatment of the derivatives with a dilute solution of iodine in methanol. 0097-6156/89/0386-0002$06.00/0 c 1989 American Chemical Society In Trends in Synthetic Carbohydrate Chemistry; Horton, D., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1989.