Fortschritte der Chemie organischer Naturstoffe / Progress in the Chemistry of Organic Natural Products

213 Pages·1993·13.26 MB·English

by  Prof. W. Herz, Prof. G. W. Kirby, Prof. R. E. Moore, Prof. Dr. W. Steglich, Prof. Dr. Ch. Tamm (eds.), Prof. D. G. I. Kingston, A. A. Molinero, J. M. Rimoldi (auth.)

FortsehriHe der Chemie organiseher Naturstoffe
Progress in the Chemistl7
of Organie Natural Produets
6!
Fo.,,.ded ~ L Zeelameister
Edited ~ We Berz, G. We Kir~, R. E. Moore,
We Ste,liela, lI,.d Cia. Tllmm
Authors:
D.G.I. Kingston, A.A. Molinero, J.M. Rinaoldi
Springer-Verlag
Wien NewYorll 1993
Prof. W. HERZ, Department of Chemistry,
The Florida State University, Tallahassee, Florida, U.S.A.
Prof. G. W. KIRBY, Chemistry Department,
The University, Glasgow, Scotland
Prof. R. E. MOORE, Department of Chemistry,
University of Hawaii at Manoa, Honolulu, Hawaii, U.S.A.
Prof. Dr. W. STEGLICH, Institut fUr Organische Chemie der Universitat
Munchen, Munchen, Federal Republic of Germany
Prof. Dr. CH. TAMM, Institut fUr Organische Chemie der Universitiit Basel,
Basel, Switzerland
This work is subject to copyright.
All rights are reserved, whether the whole or part of the material is concerned, specifically those
of translation, reprinting, re-use of illustrations, broadcasting, reproduction by photocopying
machines or similar means, and storage in data banks.
© 1993 by Springer-Verlag/Wien
Softcover reprint of the hardcover 1st edition 1993
Library of Congress Catalog Card Number AC 39-1015
Typesetting: Macmillan India Ltd., Bangalore-25
With 4 Figures
ISSN 0071-7886
ISBN-13: 978-3-7091-9244-3 e-ISBN-13: 978-3-7091-9242-9
DOl: 10.1007/978-3-7091-9242-9
Contents
list of Contributors . . IX
The Taxane Diterpenoids
By D.G.1. KINGSTON, A. A. MOLINERO, and I.M. RIMOLDI
1. Introduction. . . . . . . . . . . . . . . 3
2. General Structural Characteristic and Nomenclature 8
3. The Families of Taxane Diterpenoids. . . . . . 10
3.1. Taxoids with a C-4(20) Exocyclic Double Bond. 11
3.2. Taxoids with a C-4(20) Epoxide 22
3.3. Taxoids with an Oxetane Ring. 22
3.4. Miscellaneous Taxoids . 32
4. The Chemistry of the Taxoids 32
4.1. Isolation Techniques . . 32
4.1.1. Extraction. . . . 32
4.1.2. Purification and Analysis 33
4.2. Spectroscopy. . . . . . . 35
4.2.1. UV and ORDjCD Spectroscopy. 35
4.2.2. Infrared Spectroscopy. . 37
4.2.3. IH-NMR Spectroscopy. 37
4.2.4. 13C_NMR Spectroscopy. 39
4.2.5. Mass Spectrometry . 53
4.2.6. X-ray Crystallography . 60
4.3. Chemical Reactivity . . . . 62
4.3.1. Acylation and Other Protective Group Chemistry. 62
4.3.2. Hydrolysis . . . . 66
4.3.3. Epimerization at C-7 . 68
4.3.4. Oxidation. . . . . 69
4.3.5. Reduction. . . . . 73
4.3.6. Rearrangements and Related Reactions 76
4.3.7. Photochemistry. . . . . . . . . 80
5. Approaches to the Synthesis of Taxane Diterpenoids 81
5.1. Linear Strategies . . . . . 83
5.1.1. Biomimetic Approaches. 83
5.1.1.1. Kato's Approach 83
5.1.1.2. Frejd's Approach 85
5.1.1.3. Pattenden's Approach. 86
VI Contents
5.1.2. Intramolecular Diels-Alder Approaches 88
5.1.2.1. Shea's Approach. . 88
5.1.2.2. Jenkin's Approach. 90
5.1.2.3. Sakan's Approach . 92
5.1.2.4. Yadav's Approach. 92
5.1.3. AB -+ ABC Approaches. . 93
5.1.3.1. Martin's Approach. 93
5.1.3.2. Holton's Approaches: The Synthesis of Taxusin . 94
5.1.3.3. Oishi's Approach . . . . 96
5.1.3:4. Fetizon's Second Approach. . . . . 99
5.1.3.5. Blechert's Second Approach. . . . . 100
5.1.3.6. Wender's CoRing Annulation Approach 101
5.1.3.7. Kraus' Approach . . . 102
5.1.3.8. Yamada's Approach . . 102
5.1.3.9. Fetizon's Third Approach 103
5.1.3.10. Gadwood's Approach 104
5.1.4. BC -+ ABC Approaches. . . . 105
5.1.4.1. Swindell's Approach . . 105
5.1.4.2. Wender's A-Ring Annulation Approach 108
5.1.4.3. Sieburth's Approach . 110
5.1.4.4. Kanematsu's Approach 111
5.2. Convergent Strategies. . . . . . 113
5.2.1. AC -+ ABC Approaches. . . 113
5.2.1.1. Kitagawa's Approach . 114
5.2.1.2. Fetizon's First Approach. 116
5.2.1.3. Kende's Approach. . 118
5.2.1.4. Funk's Approach . . 120
5.2.1.5. Kuwajima's Approach. 120
5.2.2. A[B]C -+ ABC Approaches . 121
5.2.2.1. Trost's Approach . . 121
5.2.2.2. Inouye's First Approach . 123
5.2.2.3. Blechert's First Approach 125
5.2.2.4. Clark's Approach . . . 126
5.2.2.5. Berkowitz's Approach. . 127
5.2.2.6. Inouye's Second Approach 129
5.2.2.7. Winkler's Approach . . 131
5.2.2.8. A Variation on Fetizon's Second Approach 133
5.2.2.9. Ghosh's Approach. . 134
5.2.2.10. Paquette's Approach. 136
5.2.2.11. Snider's Approach. . 140
5.2.2.12. Zucker's Approach . 142
5.2.2.13. Frejd's Synthesis of a Secotaxoid 142
5.3. Partial Synthesis of Taxol and Related Compounds 143
5.3.1. Synthesis of Taxol and Taxol Analogues from
13-Cinnamoylbaccatin III . . . . . . . 143
5.3.2. Synthesis of Taxol by Acylation of Baccatin III
with a Pre-formed Side Chain. . . . . . . 145
5.3.3. Acylation of Baccatin III with II-Lactams or Oxazinones 149
5.3.4. Synthesis of Taxol Analogues . 150
5.3.5. Synthesis of Oxetane Models. . . . . . . . . . 151
Contents VII
6. Biosynthesis and Biotransformation of Taxoids 154
6.1. Biosynthesis of Taxoids . . . . 154
6.2. Biotransformation of Taxoids. . 159
7. Bioactivity of Taxol and Other Taxoids 160
7.1. Toxicity of Taxus Alkaloids. . . 160
7.2. Biological Activity of Taxol and Related Compounds. 161
7.2.1. Antitumor Activity of Taxol . . . . . . . 161
7.2.2. Microtubule Assembly Activity of Taxol. . . . 163
7.2.3. Structure-activity Relationships of Taxol Analogs. 165
Addendum ... 165
Acknowledgements 173
References . 173
Author Index 193
Subject Index 201
List of Contributors
KINGSTON, Prof. D.G.I., Department of Chemistry, Virginia Polytechnic Institute and State
University, Blacksburg, Virginia 24061, U.S.A.
MOLINERO, A.A., Department of Chemistry, Virginia Polytechnic Institute and State
University, Blacksburg, Virginia 24061, U.S.A.
RIMOLDI, I.M., Department of Chemistry, Virginia Polytechnic Institute and State Univer-
sity, Blacksburg, Virginia 24061, U.S.A.
The Taxane Diterpenoids
D.G.I. KINGSTON, A.A. MOLINERO, and 1M. RIMOLDI, Department of
Chemistry, Virginia Polytechnic Institute and State University,
Blacksburg, Virginia, 24061-0212, USA
Contents
1. Introduction. . . . . . . . . 3
2. General Structural Characteristic and Nomenclature 8
3. The Families of Taxane Diterpenoids. . . . . . 10
3.1. Taxoids with a C-4(20) Exocyclic Double Bond. 11
3.2. Taxoids with a C-4(20) Epoxide 22
3.3. Taxoids with an Oxetane Ring. 22
3.4. Miscellaneous Taxoids . 32
4. The Chemistry of the Taxoids 32
4.1. Isolation Techniques . . 32
4.1.1. Extraction. . . . 32
4.1.2. Purification and Analysis 33
4.2. Spectroscopy. . . . . . . 35
4.2.1. UV and ORD/CD Spectroscopy. 35
4.2.2. Infrared Spectroscopy. . 37
4.2.3. lH-NMR Spectroscopy. 37
4.2.4. 13C-NMR Spectroscopy. 39
4.2.5. Mass Spectrometry . 53
4.2.6. X-ray Crystallography . 60
4.3. Chemical Reactivity . . . . 62
4.3.1. Acylation and Other Protective Group Chemistry. 62
4.3.2. Hydrolysis . . . . 66
4.3.3. Epimerization at C-7 . 68
4.3.4. Oxidation. . . . . 69
4.3.5. Reduction. . . . . 73
4.3.6. Rearrangements and Related Reactions 76
4.3.7. Photochemistry. . . . . . . . . 80
5. Approaches to the Synthesis of Taxane Diterpenoids 81
5.1. Linear Strategies . . . . . 83
5.1.1. Biomimetic Approaches. 83
5.1.1.1. Kato's Approach 83
2 D.G.I. KINGSTON, A.A. MOLINERO and J.M. RIMOLDI
5.1.1.2. Frejd's Approach . . . . . 85
5.1.1.3. Pattenden's Approach. . . . 86
5.1.2. Intramolecular Diels-Alder Approaches 88
5.1.2.1. Shea's Approach. 88
5.1.2.2. Jenkin's Approach 90
5.1.2.3. Sakan's Approach 92
5.1.2.4. Yadav's Approach 92
5.1.3. AB -+ ABC Approaches. 93
5.1.3.1. Martin's Approach. 93
5.1.3.2. Holton's Approaches: The Synthesis of Taxusin . 94
5.1.3.3. Oishi's Approach . . . . 96
5.1.3.4. Fetizon's Second Approach. . . . . 99
5.1.3.5. Blechert's Second Approach. . . . . 100
5.1.3.6. Wender's C-Ring Annulation Approach 101
5.1.3.7. Kraus' Approach . . . 102
5.1.3.8. Yamada's Approach . . 102
5.1.3.9. Fetizon's Third Approach 103
5.1.3.10. Gadwood's Approach 104
5.1.4. BC ..... ABC Approaches. . . . 105
5.1.4.1. Swindell's Approach . . 105
5.1.4.2. Wender's A-Ring Annulation Approach 108
5.1.4.3. Sieburth's Approach . 110
5.1.4.4. Kanematsu's Approach 111
5.2. Convergent Strategies. . . . . . 113
5.2.1. AC ..... ABC Approaches. . . 113
5.2.1.1. Kitagawa's Approach. 114
5.2.1.2. Fetizon's First Approach. 116
5.2.1.3. Kende's Approach. . 118
5.2.1.4. Funk's Approach . . 120
5.2.1.5. Kuwajima's Approach. 120
5.2.2. A[B]C ..... ABC Approaches . 121
5.2.2.1. Trost's Approach . . 121
5.2.2.2. Inouye's First Approach . 123
5.2.2.3. Blechert's First Approach 125
5.2.2.4. Clark's Approach . . . 126
5.2.2.5. Berkowitz's Approach. . 127
5.2.2.6. Inouye's Second Approach 129
5.2.2.7. Winkler's Approach . . 131
5.2.2.8. A Variation on Fetizon's Second Approach 133
5.2.2.9. Ghosh's Approach. . 134
5.2.2.10. Paquette's Approach. 136
5.2.2.11. Snider's Approach. . 140
5.2.2.12. Zucker's Approach . 142
5.2.2.13. Frejd's Synthesis of a Secotaxoid 142
5.3. Partial Synthesis of Taxol and Related Compounds 143
5.3.1. Synthesis of Taxol and Taxol Analogues from
13-Cinnamoylbaccatin III . . . . . . . 143
5.3.2. Synthesis of Taxol by Acylation of Baccatin III
with a Pre-formed Side Chain. . . . . . . 145
5.3.3. Acylation of Baccatin III with /3-Lactams or Oxazinones 149
The Taxane Diterpenoids 3
5.3.4. Synthesis of Taxol Analogues. . . 150
5.3.5. Synthesis of Oxetane Models. . . 151
6. Biosynthesis and Biotransformation of Taxoids 154
6.1. Biosynthesis of Taxoids . . . . 154
6.2. Biotransformation of Taxoids. . 159
7. Bioactivity of Taxol and Other Taxoids 160
7.1. Toxicity of Taxus Alkaloids. . . 160
7.2. Biological Activity of Taxol and Related Compounds. 161
7.2.1. Antitumor Activity of Taxol . . . . . . . 161
7.2.2. Microtubule Assembly Activity of Taxol. . . 163
7.2.3. Structure-activity Relationships of Taxol Analogs. 165
Addendum ... 165
Acknowledgements 173
References . . . 173
1. Introduction
The taxane diterpenoids form a unique class of natural products
containing the unusual taxane skeleton (1.1) or closely related skeletons
and occurring in various members of the genus Taxus (Taxaceae) and
closely related genera. Initial interest in the constituents of Taxus species
was sparked by the known toxicity of T. baccata, or the English yew,
since human fatalities due to ingestion of this plant were recorded as long
ago as the first century B.c.. Thus Julius Caesar, speaking of his wars
against the Gallic tribes, writes "Catuvolcus, who was king of half of the
Eburones and had joined Ambiorix in the conspiracy, was now old and
weak, unable to endure the hardships of war or flight. He solemnly
cursed Ambiorix for instigating the conspiracy, and then poisoned
himself with yew, a tree which is very common in Gaul and in Germany"
(27).
6
18
5
14 20
1.1
The first chemical study of a Taxus species was carried out by LUCAS
(J 63) who in 1856 isolated an ill-defined alkaloidal substance which he
named taxine. Unfortunately, although "taxine" is almost certainly