The Alkaloids: Chemistry and Pharmacology 23

421 Pages·1984·15.5 MB·English

by  Arnold Brossi (Eds.)

THE ALKALOIDS
Chemistry and Pharmacology
Volume XXIII
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THE ALKALOIDS
Chemistry and Pharmacology
Edited by
Arnold Brossi
National Institutes of Health
Bethesda. Maryland
VOLUME XXIII
1984
ACADEMIC PRESS, INC.
(Harcourf Brace Jovanovicb, Publishers)
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COPYRIG@HT 1 984, BY ACADEMIPCR ESS,I NC.
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ACADEMIC PRESS. INC.
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United Kingdom Edition published by
ACADEMIC PRESS, INC. (LONDON) LTD.
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LIBRAROYF CONOR~CSSA TALOCOA RDN UMBER:5 0-5522
ISBN 0-12-469523-X
PRINTEDNI me UNITED STATES OF AMERICA
84 85 86 87 9 8 7 6 5 4 3 2 1
CONTENTS
CONTRIBUTOR.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix
PREFACE. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi
...
CONTENTOSF PREVIOUVSO LUMES. . . . . . . . . . . . . . . . . . . . . XIII
Chapter 1 . Tropolonic Colchicum Alkaloids
HANS-GEORCGA PRAROAN D ARNOLDB ROW
I . Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
I1 . Occurrence in Nature . . . . . . . . . . . . . . . . . . . . . . . . 3
I11 . Chemistry of Colchicum Alkaloids. . . . . . . . . . . . . . . . . . . 18
IV . Novel Syntheses of Colchicine . . . . . . . . . . . . . . . . . . . . 42
V . Biological Properties of Colchicine Alkaloids . . . . . . . . . . . . . . 48
V1 . Structure-Activity Relationships . . . . . . . . . . . . . . . . . . . 51
VII . Biosynthesis of Colchicine . . . . . . . . . . . . . . . . . . . . . . 57
Addendum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
Chapter 2 . Maytansinoids
PAULJ . REIDERA ND DENNISM . ROLAND
I . Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
I1 . Isolation and Structural Variation . . . . . . . . . . . . . . . . . . . 73
I11 . Physical Properties . . . . . . . . . . . . . . . . . . . . . . . . . . 81
IV . Synthetic Approaches . . . . . . . . . . . . . . . . . . . . . . . . . 95
V . Biological Activity . . . . . . . . . . . . . . . . . . . . . . . . . . 150
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151
Chapter 3 . Cephalotaxus Alkaloids
LIANGH UANGA ND ZHI XUE
I . Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
I1 . Structural Studies on Cepphaloraxus Alkaloids. . . . . . . . . . . . . . 163
V
vi CONTENTS
111 . Syntheses of Cepphalotaxus Alkaloids . . . . . . . . . . . . . . . . . 173
IV . Nuclear Magnetic Resonance Spectroscopy and Mass Spectroscopy of
Cepphuloruxus Alkaloids . . . . . . . . . . . . . . . . . . . . . . . 191
V . Pharmacological and Clinical Studies of the Four Natural Esters of
Cephalotaxine . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197
VI . Unnatural Cephalotaxine Esters and Their Antitumor Activity . . . . . . 208
VII . Biosynthesis of Cephaloraxus Alkaloids . . . . . . . . . . . . . . . . 213
Addendum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223
Chapter 4 . Constituents of Red Pepper Species: Chemistry. Biochemistry.
Pharmacology. and Food Science of the Pungent Principle of Capsicum Species
T . SUZUKAIN D K . IWAI
I . Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . 228
I1 . Structure. Nomenclature. Chemistry. and Occurrence . . . . . . . . . . 229
111. Analysis of Capsaicin and Analogs . . . . . . . . . . . . . . . . . . 235
IV . Synthesis of Capsaicin and Analogs . . . . . . . . . . . . . . . . . . 254
V . Formation and Accumulation in Capsicum Plants . . . . . . . . . . . . 258
V1 . Nutritional. Metabolic. and Pharmacological Studies . . . . . . . . . . 272
VII . Capsaicin and Analogs as Food Constituents . . . . . . . . . . . . . . 283
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 286
Chapter 5 . Azufluoranthene and Tropoloisoquinoline Alkaloids
KEITHT . BUCK
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301
I1 . Occurrence and Structure of Azafluoranthene Alkaloids . . . . . . . . . 302
Ill . Occurrence and Structure of Tropoloisoquinoline Alkaloids . . . . . . . 307
IV . Syntheses of Azafluoranthene Alkaloids and Related Compounds . . . . . 309
V . Synthesis of Tropoloisoquinoline Alkaloids . . . . . . . . . . . . . . . 320
VI . Biosynthetic Considerations . . . . . . . . . . . . . . . . . . . . . 320
VII . Pharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323
Appendix: Proton NMR Data . . . . . . . . . . . . . . . . . . . . . 323
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324
Chapter 6 . Muscarine Alkaloids
PEN-CHUNGW ANGA ND MADELEINME . JOULLI~
I . Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . 328
I1 . Natural Occurrence of Muscarine and Stereoisomers . . . . . . . . . . 329
CONTENTS vii
I11 . Isolation of Muscarine . . . . . . . . . . . . . . . . . . . . . . . . 333
IV . Structural and Conformational Studies of Muscarine . . . . . . . . . . 334
V . Synthetic Investigations of Muscarones and Dehydromuscarones . . . . 338
VI . Synthetic Investigations of Muscarines and Stereoisomers . . . . . . . . 341
VII . Synthetic Investigations of Musca.r ine Analogs . . . . . . . . . . . . . 351
VIII . Biological Activity of Muscarines Muscarones. Their Stereoisomers. and
Analogs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 364
IX . Structure-Activity Relationships in Muscarine. Its Stereoisomers. and
Analogs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 372
X . Biosynthesis of Muscarine . . . . . . . . . . . . . . . . . . . . . . 376
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 378
INDEX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 381
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CONTRIBUTORS
Numbers in parentheses indicate the pages on which the authors’ contributions begin.
ARNOLDB ROSSI(I ), National Institutes of Health, Bethesda, Maryland
20205
KEITHT . BUCK( 301), Fries & Fries Division, Mallinckrodt, Inc., Cincin-
nati, Ohio 45216
HANS-GEORCGA PRAR(OI) , CIBA GEIGY Co., 4000 Basel, Switzerland
LIANGH UANG(1 57), Institute of Materia Medica Chinese, Academy of
Medical Sciences, Beijing, People’s Republic of China
K. IWAI( 227), Department of Food Science and Technology, Faculty of
Agriculture, Kyoto University, Kyoto 606, Japan
MADELEINEM . JOULLIB(3 27). Chemistry Department, University of
Pennsylvania, Philadelphia, Pennsylvania 19104
PAULJ . REIDER(7 1), Merck Sharp & Dohme Research Laboratories,
Rahway, New Jersey 07065
DENNISM . ROLAND(7 1), Research Department, Pharmaceuticals Divi-
sion, CIBA-GEIGY Corporation, Ardsley, New York 10502
T. SUZUK(I2 27), The Research Institute for Food Science, Kyoto Univer-
sity, Kyoto 61 1, Japan
PEN-CHUNWGA NG*( 327), Chemistry Department, University of Penn-
sylvania, Philadelphia, Pennsylvania 19104
ZHIX UE( 157), Institute of Materia Medica Chinese, Academy of Medical
Sciences, Beijing, People’s Republic of China
* Present address: Chemical Products Laboratory, Dow Chemical USA, Midland,
Michigan 48640.
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