Recent Progress in the Chemical Synthesis of Antibiotics

807 Pages·1990·17.47 MB·English

by  Kuniaki Tatsuta (auth.)

Gabor Lukacs . Masaji Ohno
(Ed.)
Recent Progress in
the Chemical Synthesis
of Antibiotics
With 170 Illustrations
Springer-Verlag
Berlin Heidelberg NewY ork London Paris
Tokyo Hong Kong Barcelona
Dr. G. Lukacs
Directeur de Recherche C.N.R.S.
Institut de Chimie des
Substances Naturelles du C.N.R.S.
Avenue de la Terrasse
F-91198 Gif-sur-Yvette Cedex, France
Prof. Dr. M. Ohno
University of Tokyo
7-3-1 Hongo, Bunkyo-ku
Tokyo 113, Japan
ISBN-13: 978-3-642-75619-1 e-ISBN-13: 978-3-642-75617-7
001: 10.1007/978-3-642-75617-7
Library of Congress Cataloging-in-Publication Data
Recent progress in the chemical synthesis of antibiotics/
Gabor Lukacs, Masaji Ohno (ed.).
Includes index.
ISBN-13: 978-3-642-75619-1 (U.S.)
1. Antibiotics - Synthesis. 2. Pharmaceutical chemistry.
3. Organic compounds - Synthesis. I. Lukacs, Gabor, 1937-
II. Ohno, Masaji, 1930-
[DNLM: 1. Antibiotics - chemical synthesis. QV 350 R2958]
RS431.A6R43 1990
615'.329 - dc20
DNLMjDLC
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fall under the prosecution act of the German Copyright Law.
© Springer-Verlag Berlin Heidelberg 1990
Softcover reprint of the hardcover 1st edition 1990
The use of registered names, trademarks, etc. in this publication does not imply, even in the absence
of a specific statement, that such names are exempt from the relevant protective laws and regulations
and therefore free for general use.
2151/3020-543210 Printed on acid-free paper.
Foreword
The use of antibiotics in the treatment by antibacterial and antifungal chemo
therapy, has become standard practice since the end of World War Two and has
had an enormous impact on healthcare throughout the world. Compounds
belonging to this class have also reached an important place in the medical
treatment of human cancer. Although, the discovery of most of these agents
came from more or less sophisticated screening programs of soil microrganisms,
many of the important antibiotics used today in clinical practice are derived
from the original biosynthetic products by the application of often novel and
generally elaborated chemical synthetic methodologies. In fact the antibiotics
have represented (and still represent) for a generation of organic chemists an
endless source of molecular structures whose varied assemblage of carbon atom
backbones and chemical functions was beyond any possibility of imagination.
Perhaps a similar repertoire of chemotypes was formerly offered by the natural
products, namely the alkaloids, the terpenes, the vitamins and hormones as well
as the pigments of the animal and plant kingdoms, albeit the chemical arrange
ments of the antibiotic molecules appeared much more surprising and diverse to
the admiring eyes of cultivated organic chemists.
The idea of this book, certainly a landmark in the field, came during the
Symposium of EUCHEM on Chemical Synthesis of Antibiotics, that was held at
Aussois in Savoy, France (May 2-6, 1988), the initiative being taken by Gabor
Lukacs to whom Masaji Ohno readily associated as a co-editor. However,
contributors are not only those who attended the symposium, and the content of
the book goes far beyond the program of the Aussois conference. This meeting
has spawned a series of conferences, the second one of which will be held in
Japan later this year whereas a third symposium will take place in Germany in
1992.
In planning the book, the Editors sought major researchers involved in the
chemical synthesis or manipulation of antibiotics in order to provide a compre
hensive view of the chemistry of these agents. Each chapter gives an account
of work done by a single research group, central issues being the synthetic
strategies and the novelty of the chemical reactions without however forgetting
the pharmacological significance of the targets.
vi Foreword
The first five chapters are concerned with the macrolides. The subjects range
from the older well-established antibacterial agents belonging to this structural
type to the newer antiparasitic drugs such as the avermectins and the milbemy
cins, and include the ansamycins and the polyenes. The depsipeptides of the
pristinamycin family are the subject of the sixth chapter. Subsequently we go
through the updating chapter on the quinolones to the one describing brilliant
chemistry on actinobolin and bactinobolin, another example of the opportun
ities that the antibiotics offer to the "maestri" of the contemporary art of
synthetic organic chemistry. Then follow the chapters on major drugs such as
the nucleosides and lincomycin, and the one on the rationally designed antican
cer agents based on the bleomycin mechanism of action. Here we have an
illuminating example of the new approach, based on molecular engineering,
aimed at improving the affinity for the receptor site. Four other families of
antibiotics are dealt with in chapters 12 through 15, namely the mitomycins, the
polyethers, the anthracyclines and related antibiotics, all contributions being
presented by well known experts in the fields. Finally the last five chapters, all
concerned with the brightest (since the fundamental contribution of E.B. Chain)
stars of the antibiotic firmament, the beta lactams. These outstanding chemicals
are presented in their diversity embracing a wide range of creative efforts and
elegant synthetic complexity. Small molecules are more beautiful in this case?
Not necessarily so. These final chapters do not need any comment, they must be
read.
I trust that this book will provide an up-to-date account of the chemistry of
most important antibiotics. It is hoped that the readers will be stimulated to
explore further this synthetic field that, even in these times in which so great
attention is paid by the medicinal chemists to exciting issues like molecular
recognition and computer aided drug design, still proves intellectually fulfilling
and is endowed with industrial priority.
June, 1990 Federico Arcamone
Table of Contents
Total Synthesis of Macrolide Antibiotics
K. Tatsuta . ................. . 1
Structural Modification of Macrolide Antibiotics
H. Kirst . ............ . 39
Av ermectins and Milbemycins
T. Blizzard, M. Fisher, H. Mrozik, T. Shih .. 65
Ansamacrolides
M. Isobe . .... 103
Polyene Macrolides: Stereostructural Elucidation and Synthetic Studies
of a Few Members
J.-M. Beau ..................................... 135
The Chemistry of Pristinamycins
J.-M. Paris, J.-e. Barriere, e. Smith, P.-E. Bost. 183
Recent Advances in the Chemistry of Quinolones
D. Bouzard ...................... . 249
Actinobolin and Bactobolin: Chemical Aspects and Syntheses
B. Fraser-Reid, J.e. Lopez ..................... . 285
Nucleosides: Potential Drugs for AIDS Therapy
F. De las Heras, M.-J. Camarasa, J.-M. Fiandor . . .......... 321
Total Synthesis of Lincomycin and Related Chemistry
A. Golebiowski, J. Jurczak ................ . 365
Synthetic Study on Man-Made BleQmycins Based on the Anticancer
Mechanism of Natural Bleomycins
M. Ohno, M. Otsuka. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 387
Synthesis of Mitomycins
W.A. Remers, B. Iyengar 415
viii Table of Contents
Total Synthesis of Polyether Antibiotics
O. Yonemitsu, K. Horita . .......... . 447
Synthesis of Anthracyclines Related to Daunomycin
G.J. Thomas . ................... . 467
Synthesis of Polynuclear Aromatic Antibiotics
A. V. Rama Rao . ..................... . 497
Synthetic Aspects of Monocyclic ~-Lactam Antibiotics
R.C. Thomas ........................ . 533
Recent Advances in the Synthesis of PS-5 and PS-6 Antibiotics and Related
Carbapenem Compounds
C. Palomo. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 565
Synthesis of Penems
E. Perrone, G. Franceschi .. 613
1-0xacephem Antibiotics
M. Narisada, T. Tsuji . ..................... . 705
Non-~-Lactam Analogs of Penicillins and Cephalosporins
J. Marchand-Brynaert, L. Ghosez 727
Subject Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 795
List of Authors
Jean-Claude Barriere,
Rhone-Poulenc Sante, Centre de Recherches de Vitry-Alfortville, 13, quai Jules
Guesde, F-94403 Vitry sur Seine Cedex, France
Jean-Marie Beau,
Universite d'Orleans, Laboratoire de Biochimie Structurale, Unite Associee 499
du CNRS, BP 6759, F-45067 Orleans Cedex 2, France
Timothy A. Blizzard,
Merck Sharp and Dohme Research Laboratory, P.O. Box 2000, Rahway, New
Jersey 07065, USA
Pierre-Etienne Bost,
Rhone-Poulenc Sante, Centre de Recherches de Vitry-Alfortville, 13, quai Jules
Guesde, F-94403 Vi try sur Seine Cedex, France
Daniel Bouzard,
Bristol-Myers S.A., Research Laboratories, BP 62, F-77422 Marne La Vallee
Cedex 2, France
Maria-Jose Camarasa,
Instituto de Quimica Medica, Juan de la Cierva 3, 28006 Madrid, Spain
Jose-Maria Fiandor,
Instituto de Quimica Medica, Juan de la Cierva 3, 28006 Madrid, Spain
Michael H. Fisher,
Merck Sharp and Dohme Research Laboratory, P.O. Box 2000, Rahway, New
Jersey 07065, USA
Giovanne Franceschi,
Farmitalia Carlo Erba, Infectious Diseases Department, 1-20146 Milano, Italy
Bertram O. Fraser-Reid,
Department of Chemistry, Paul M. Gross Chemical Laboratory, Duke Univer
sity, Durham, North Carolina 27706, USA
x List of Authors
Leon Ghosez,
Universite Catholique de Louvain, Laboratoire de Chimie Organique de Syn
these, Place Louis Pasteur 1, B-1348 Louvain-La-Neuve, Belgium
Adam Golebiowski,
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44,
01-224 Warszawa, Poland
Federico Gomez De las Heras,
Instituto de Quimica Medica, Juan de la Cierva 3, 28006 Madrid, Spain
Kiyoshi Horita,
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
Minoru Isobe,
Laboratory for Organic Chemistry, Faculty of Agriculture, Nagoya University,
Chikusa-ku, Nagoya 464, Japan
Bhashyam S. Iyengar,
Department of Pharmaceutical Sciences, University of Arizona, Tucson,
Arizona 85721, USA
Janusz Jurczak,
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44,
01-224 Warszawa, Poland
Herbert A. Kirst,
Fermentation Products Res. Div., Lilly Research Laboratories, Eli Lilly and
Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA
J. Cristobal Lopez,
Department of Chemistry, Paul M. Gross Chemical Laboratory, Duke Univer
sity, Durham, North Carolina 27706, USA
Jacqueline Marchand-Brynaert,
Universite Catholique de Louvain, Laboratoire de Chimie Organique de Syn
these, Place Louis Pasteur 1, B-1348 Louvain-La-Neuve, Belgium
Helmut Mrozik,
Merck Sharp and Dohme Research Laboratory, P.O. Box 2000, Rahway, New
Jersey 07065, USA
Masayuki Narisada,
Shionogi Research Laboratories, Shionogi & Co. Ltd., Fukushima-ku, Osaka
553,Japan
List of Authors xi
Masaji Ohno,
Faculty of Pharmaceutical Sciences, University of Tokyo, Hongo, Bunkyo-ku,
Tokyo 113, Japan
Masami Otsuka,
Faculty of Pharmaceutical Sciences, University of Tokyo, Hongo, Bunkyo-ku,
Tokyo 113, Japan
Claudio Palomo, Departmento de Quimica Aplicada, Unidad de Quimica
Organica, Facultad de Ciencias Quimicas, Universidad de Pais Vasco, Apdo.
1072, 20080 San Sebastian, Spain
Jean-Marc Paris,
Rhone-Poulenc Sante, Centre de Recherches de Vitry-Alfortville, 13, quai Jules
Guesde, F-94403 Vitry sur Seine Cedex, France
Ettore Perrone,
Farmitalia Carlo Erba, Infectious Diseases Department, 1-20146 Milano, Italy
A.V. Rama Rao,
Indian Institute of Chemical Technology, Hyderabad 500 007, India
Willian Alan Remers,
Department of Pharmaceutical Sciences, University of Arizona, Tucson,
Arizona 85721, USA
Thomas L. Shih,
Merck Sharp and Dohme Research Laboratory, P.O. Box 2000, Rahway, New
Jersey 07065, USA
Christopher Smith,
Rhone-Poulenc Ltd., Dagenham Research Centre, Rainham Road South,
Dagenham, Essex RMI0 7XS, United Kingdom
Kuniaki Tatsuta,
Department of Applied Chemistry, Faculty of Science and Technology, Keio
University, 3-14-1 Hiyoshi, Kohoku, Yokohama 223, Japan
Gareth John Thomas,
Research Division, Roche Products Limited, P.O. Box 8, Welwyn Garden City,
Hertfordshire AL 7 3A Y, United Kingdom
Richard C. Thomas,
Cancer and Infectious Diseases Research, The Upjohn Company, Kalamazoo,
MI 49001, USA