Antitumor Bisindole Alkaloids from (L.)

261 Pages·1990·9.67 MB·English

by  Arnold Brossi and Matthew Suffness (Eds.)

THE ALKALOIDS
Antitumor Bisindole Alkaloids
from Cutharunthus roseus (L.)
VOLUME 37
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THE ALKALOIDS
Antitumor Bisindole Alkaloids from
Catharanthus roseus (L.)
Edited by
Arnold Brossi
National Institutes of Health
Bethesda, Maryland
Matthew Suffness
National Cancer Institute
National Institutes of Health
Bethesda, Maryland
VOLUME 37
Academic Press, Inc.
Harcourt Brace Jovanovich, Publishers
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London Sydney Tokyo Toronto
This book is printed on acid-free paper. @
COPYRIGHT 0 1990 BY ACADEMIC PRESS, INC.
All Rights Reserved.
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from the publisher.
ACADEMIC PRESS, INC.
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United Kingdom Edition published by
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LIBRARY OF CONGRESS CATALOG CARD NUMBER: 50-5522
ISBN 0-12-469537-X (alk. paper)
PRINTED IN THE UNITED STATES OF AMERICA
90 91 92 93 9 8 7 6 5 4 3 2 I
CONTENTS
CONTRIBUTO.R..S.. .................................................................................. vii
PREFACE ................................................................................................ ix
Chapter 1 . Isolation. Structure Elucidation. and Biosynthesis of the Bisindole
Alkaloids of Curhurunrhus
GABORB LASK6 AND GEOFFREYA . CORDELL
1. Introduction .................................................................................. 1
11 . Structure Elucidation and Spectroscopy ............................................. 5
Ill . Biosynthesis .................................................................................. 36
IV . Summary ...................................................................................... 67
References .................................................................................... 69
Chapter 2 . Syntheses of Vinblastine-Type Alkaloids
MARTINE . KUEHNEAN D kTVAN MARK6
1. Introduction .................................................................................. 77
11 . Hydroxyalkylindole Route ............................................................... 79
111. Chloroindolenine Route ................................................................... 81
IV . P-Carboline Coupling ...................................................................... 89
V. Biomimetic Approach ...................................................................... 89
VI . New Strategies for Generation of C-16’-C-14’ PARF Relative
Stereochemistry ............................................................................. 105
References .................................................................................... 127
Chapter 3 . Functional Hot Spot at the C-20‘ Position of Vinblastine
LINDAS . BORMANA ND MARTINE . KuEHNE
I . Introduction .................................................................................. 133
I1. C-20’ Modifications. ........................................................................ 134
I11 . Molecular Constraints of Congener Activity ........................................ 142
IV . Conclusions ................................................................................... 144
References .................................................................................... 144
V
vi CONTENTS
Chapter 4 . Medicinal Chemistry of Bisindole Alkaloids From Curharunthus
H . L . PEARCE
I . Introduction .................................................................................. i45
I1 . Pharmacology ................................................................................ i47
111. Physicochemical Considerations ........................................................ 149
IV . Naturally Occurring Bisindole Alkaloids from Cutlzurunrhus .................. 153
V . Modifications of the Upper Half (Velbanamine Portion) of Bisindole
Alkaloids ...................................................................................... 155
VI . Modifications of the Lower Half (Vindoline Portion) of Bisindole Alkaloids 166
VII . Multiple Modifications: 4'-Epideoxyvincristine .................................... 186
VIII . New Concepts in Medicinal Chemistry of Bisindole Alkaloids ................ 190
IX . Conclusions ................................................................................... 199
References .................................................................................... 200
Chapter 5 . Pharmacology of Antitumor Bisindole Alkaloids from Curhurunrhus
JOHNJ . MCCORMACK
I . Introduction .................................................................................. 205
I1 . Biochemical Pharmacology ............................................................... 207
111 . Cellular Pharmacology ..................................................................... 209
IV . Preclinical Pharmacology ................................................................. 214
V . Preclinical Toxicology ..................................................................... 220
VI. Clinical Pharmacology ..................................................................... 222
VII . Clinical Toxicology ......................................................................... 224
References .................................................................................... 226
Chapter 6 . The Therapeutic Use of Bisindole Alkaloids from Catharunthus
NORBERTN EUSSA ND MICHAELN . NEUSS
I . History of Therapeutic Use .............................................................. 229
I1 . Current Therapeutic Use ................................................................. 232
Ill . Toxicity ........................................................................................ 235
IV . Mechanism of Action ...................................................................... 237
V . Drug Resistance ............................................................................. 238
References .................................................................................... 239
CUMULATIVINED EX OF TITLES.. ............................................................... 24 1
INDEX ................................................................................................... 247
CONTRIBUTORS
Numbers in parentheses indicate the pages on which the authors’ contributions begin.
GABORB LASKO( l), Central Research Institute for Chemistry, Hungarian
Academy of Sciences, Budapest H- 1525, Hungary
LINDAS . BORMAN(1 33), Department of Pharmacology and Vermont Re-
gional Cancer Center, University of Vermont, Burlington, Vermont
05405
GEOFFREYA . CORDELL(I ), Program for Collaborative Research in the
Pharmaceutical Sciences, College of Pharmacy, University of Illinois
at Chicago, Chicago, Illinois 60612
MARTINE . KUEHNE( 77, 133), Department of Chemistry and Vermont
Regional Cancer Center, University of Vermont, Burlington, Vermont
05405
ISTVANM ARKO( 77), Department of Chemistry, The University of Shef-
field, Shefield S37HP, England
JOHNJ . MCCORMACK(2 05), Department of Pharmacology, University of
Vermont, Burlington, Vermont 05405
MICHAELN . NEWS (229), Oncology and Hematology, Cincinnati, Ohio
252 19
NORBERTN EWS (229), formerly of Lilly Research Laboratories, Eli Lilly
and Company, Indianapolis, Indiana 46285
H. L. PEARCE(1 45), Lilly Research Laboratories, Eli Lilly and Com-
pany, Indianapolis, Indiana 46285
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PREFACE
This volume entitled “Bisindole Alkaloids from Catharanthus roseus
(L.),” commonly called Vinca alkaloids, Catharanthus alkaloids, or di-
meric Vinca alkaloids, was written by a group of internationally known
experts. It provides for the first time, a comprehensive view of the basic
chemistry, biogenesis, synthesis, medicinal chemistry, pharmacology,
and medical uses of these important antitumor agents. Because of the
complex structures of the alkaloids, the transformations within the basic
series, such as the medicinal chemistry, are best presented using the
Chemical Abstracts numbering system, while the transformations be-
tween series, as in the total synthesis, are presented using the biosyn-
thetic numbering system. We apologize if the reader finds the exposure
to two numbering systems confusing.
This treatise is a companion work to Volume 25 of this series entitled
“Antitumor Alkaloids,” which covers all classes except the bisindole al-
kaloids presented here.
Matthew Suffness
Arnold Brossi
National Institutes of Health
ix