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

260 Pages·2002·4.854 MB·English

by  M. Glasenapp-Breiling, P. G. Jagtap, D. G. I. Kingston, F.-P. Montforts, L. Samala, H. Yuan (auth.), Prof. W. Herz, Prof. H. Falk, Prof. G. W. Kirby (eds.)

84
Fortschritte der Chemie
organischer Na turstoffe
Progress in the
Chemistry of Organic
Natural Products
Founded by
L. Zechmeister
Edited by
W Herz, H. Falk,
and G. W Kirby
Authors:
M. Glasenapp-Breiling, P. G. Jagtap,
D. G. I. Kingston, F.-P. Montforts,
L. Samala, H. Yuan
SpringerW ienN ew York
Prof. W. Herz, Department of Chemistry,
The Florida State University, Tallahassee, Florida, U.S.A.
Prof. H. Falk, Institut fUr Chemie,
10hannes-Kepler-Universitat, Linz, Austria
Prof. G. W. Kirby, Chemistry Department,
The University of Glasgow, Glasgow, Scotland
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ISBN 978-3-7091-3228-9 ISBN 978-3-7091-6160-9 (eBook)
DOI 10.1007/978-3-7091-6160-9
Softcover reprint of the hardcover 1s t edition 2002
2002 by Springer-Verlag Wien
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Contents
List of Contributors ........................................... VIII
Naturally Occurriug Cyclic Tetrapyrro\es
F.-P. Montforts and M. Glasenapp-Breiling .......................... .
1. Introduction .............................................. 2
2. Classification ............................................. 3
3. General Aspects of Cyclic Tetrapyrrole Biosynthesis . . . . . . . . . . . . . . . . . . 5
4. Porphyrins ............................................... 9
4.1. Occurrence, Structure, and Biological Function .................. 9
4.2. Biosynthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
4.3. Aspects of Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
5. Chlorins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
5.1. Occurrence, Structure, and Biological Activity .................. , 14
5.2. Biosynthesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 18
5.3. Aspects of Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 20
6. Bacteriochlorins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 23
6.1. Occurrence, Structure, and Biological Activity . . . . . . . . . . . . . . . . . . . 23
6.2. Aspects of Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
7. Isobacteriochlorins ......................................... , 27
7.1. Occurrence, Structure, and Biological Activity . . . . . . . . . . . . . . . . . .. 27
7.2. Biosynthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 29
7.3. Aspects of Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 29
8. Higher Saturated Hydroporphyrins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
8.1. Occurrence, Structure, and Biological Activity . . . . . . . . . . . . . . . . . .. 32
8.2. Biosynthesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 36
9. Corrins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 36
Acknowledgments 42
References ................................................. 42
VI Contents
The Chemistry of Taxol and Related Taxoids
By D. G. I. Kingston, P. G. Jagtap, H. Yuan, and L. Samala ............. . 53
1. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
2. A-Ring Chemistry ....................................... . 57
2.1. Modifications of the 11,12-Double Bond .................... . 58
2.2. Modifications at C-13 ................................. . 60
2.3. Modifications at C-14 ................................. . 62
2.4. Modifications at C-18 65
3. B-Ring Chemistry ....................................... . 66
3.1. Modifications at C-1O ................................. . 66
3.2. Modifications at C-9 .................................. . 73
3.3. Modifications at C-19 ................................. . 75
304. Modifications at C-2 .................................. . 76
3.5. Modifications at C-l .................................. . 80
3.6. Other B-Ring Analogs ................................. . 81
3.7. SAR of B-Ring Analogs ............................... . 82
4. C-Ring Chemistry ....................................... . 85
4.1. The C-7 Hydroxyl Group ............................... . 85
4.2. Products Derived from 6,7-Dehydrotaxol .................... . 93
4.3. Modifications at C-4 .................................. . 96
5. D-Ring Chemistry ....................................... . 100
5.1. Ring Opening by Electrophiles ........................... . 101
5.2. Ring-Opening by Nucleophiles ........................... . 102
5.3. D-Ring Analogs ..................................... . 102
504. Spectroscopic and Theoretical Studies ...................... . 105
6. Rearrangements and Related Reactions ........................ . 105
6.1. Rearrangements Leading to 11(15->1)-abeo taxols (A-nortaxols) ... . 106
6.2. Rearrangements Involving the B-Ring ...................... . 108
6.3. Rearrangements Involving Both A- and B-Rings ............... . 110
604. Rearrangements of Ring C .............................. . 112
7. The Side Chain .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
7.1. Synthesis of the Side Chain by the -lactam Approach ........... . 113
7.2. Synthesis of the Side Chain via an Epoxide Intermediate ......... . 116
7.3. Synthesis of the Side Chain by Sharpless Asymmetric
Aminohydroxylation .................................. . 118
7 A. Synthesis of the Side Chain by Coupling Reactions ............ . 119
7.5. Synthesis of Cyclically Protected Side Chains ................ . 122
7.6. Miscellaneous Syntheses ............................... . 124
7.7. Syntheses of Phosphonate Side Chain Analogs ................ . 126
8. Synthesis of Taxol and Taxol Side Chain Analogs from Baccatin III .... . 126
8.1. Synthesis of Taxol and Docetaxel ......................... . 126
8.2. Synthesis of N-Acyl Analogs of Taxol ..................... . 129
8.3. Synthesis of 3'-AryI Analogs of Taxol ...................... . 130
804. Taxol Analogs with Modified N-Acyl and 3'-Aryl Groups ........ . 131
8.5. Taxol Analogs Modified Both on the Side Chain and the
Ring System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
Contents VII
8.6. Synthesis of Taxol Analogs with Highly Modified Side Chains. . . . . . 133
8.7. Side Chain Chemistry .................................. 135
9. Taxol Metabolites ........................................ 136
10. Taxol Analogs and Prodrugs ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
10.1. Simple Ester Derivatives and Prodrugs ..................... 138
10.2. Phosphate Ester and other Prodrugs . . . . . . . . . . . . . . . . . . . . . . . . 139
10.3. Taxol Analogs with Polymeric Acyl Substitutions. . . . . . . . . . . . . . 140
10.4. Targeted Analogs of Taxol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
11. Labeled Taxol Analogs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142
11.1. Isotopically Labeled Taxols ............................. 142
11.2. Photoaffinity Labeled Taxols ............................ 143
11.3. Fluorescent and Other Labeled Taxols . . . . . . . . . . . . . . . . . . . . . . 145
12. The Synthesis of Taxol and Taxol Analogs from Precursors
other than Baccatin III . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148
13. The Synthesis of Simplified and Unusual Taxol Analogs ............. 153
13.1. Simplified Analogs ................................... 153
13.2. Dimeric Analogs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154
14. The Synthesis of Taxol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
14.1. The Holton Synthesis ................................. 157
14.2. The Nicolaou Synthesis .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158
14.3. The Danishefsky Synthesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
14.4. The Wender Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163
14.5. The Kuwajima Synthesis ............................... 165
14.6. The Mukaiyama Synthesis .............................. 167
15. The Interaction of Taxol with Tubulin .......................... 169
15.1. Photoaffinity Labeling Studies ........................... 171
15.2. Fluorescence Spectroscopic Studies . . . . . . . . . . . . . . . . . . . . . . . . 171
15.3. Nuclear Magnetic Resonance Studies ...................... 173
15.4. The Taxol Pharmacophore .............................. 175
Addendum ................................................ 179
Acknowledgements .......................................... 193
References ................................................ 193
Author Index .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227
Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 245
List of Contributors
Glasenapp-Breiling, Dr. M., Institut flir Organische Chemie, FB 2 Biologie/Chemie,
Universitat Bremen, Postfach 330440, D-28334 Bremen, Germany
Jagtap, Dr. P. G., Department of Chemistry, MlC 0212, Virginia Polytechnic Institute and
State University, Blacksburg, VA 24061, U.S.A. (current address: Laboratory for Drug
Discovery in Neurodegeneration, Harvard Center for Neurodegencration and Repair,
65 Landsdowne Street, Cambridge, MA 02139, U.S.A.)
Kingston, Univ. Dist. Prof. D. G. 1., Department of Chemistry, M/C 0212, Virginia
Polytechnic Institute and State University, Blacksburg, VA 24061, U.S.A.
Montforts, Prof. Dr. F.-P., Institut flir Organische Chemie, FB 2 Biologie/Chemie,
Universitat Bremen, Postfach 330440, D-28334 Bremen, Germany
Samala, Dr. L., Department of Chemistry, M/C 0212, Virginia Polytechnic Institute and
State University, Blacksburg, VA 24061, U.S.A. (current address: Combinatorial and
Medicinal Chemistry, Pharmacia Corporation, 7000 Portage Road, Kalamazoo, MI
49001, U.S.A.)
Yuan, Dr. H., Department of Chemistry, M/C 0212, Virginia Polytechnic Institute and
State University, Blacksburg, VA 24061, U.S.A. (current address: Allergan Inc., 2525
Dupont Dr., Mail Code RD-3D, Irvine, CA 92623, U.S.A.)
Naturally Occurring Cyclic Tetrapyrroles*
F.-P. Montforts and M. Glasenapp-Breiling
Institut fiir Organische Chemie, Universitat Bremen,
Bremen, Germany
Contents
1. Introduction .............................................. 2
2. Classification ............................................. 3
3. General Aspects of Cyclic Tetrapyrrole Biosynthesis . . . . . . . . . . . . . . . . . . 5
4. Porphyrins ............................................... 9
4.1. Occurrence, Structure, and Biological Function .................. 9
4.2. Biosynthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
4.3. Aspects of Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
5. Chlorins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
5.1. Occurrence, Structure, and Biological Activity. . . . . . . . . . . . . . . . . .. 14
5.2. Biosynthesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
5.3. Aspects of Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 20
6. Bacteriochlorins. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
6.1. Occurrence, Structure, and Biological Activity . . . . . . . . . . . . . . . . . .. 23
6.2. Aspects of Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
7. Isobacteriochlorins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 27
7.1. Occurrence, Structure, and Biological Activity. . . . . . . . . . . . . . . . . .. 27
7.2. Biosynthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 29
7.3. Aspects of Synthesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 29
8. Higher Saturated Hydroporphyrins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 32
8.1. Occurrence, Structure, and Biological Activity . . . . . . . . . . . . . . . . . .. 32
8.2. Biosynthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 36
9. Corrins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
Acknowledgments ............................................ 42
References ................................................. 42
* Dedicated to Professor L. F. Tietze on the occasion of his 60th birthday.
2 F.-P. Montforts and M. Glasenapp-Breiling
1. Introduction
Of the porphyrinoid structures occurring in nature the most important
and most widespread are the red blood pigment heme (1), the green
pigment of plant photosynthesis chlorophyll a (2), the bacterial photo
synthetic pigment bacteriochlorophyll a (3), and the "antipernicious"
red pigment vitamin BJ2 (4). The basic function of these cofactors
are determined by the incorporation of the different metal ions into the
macrotetracycles. The different oxidation levels of the macrocyclic
ligand system regulate the fine tuning of these functions. The final
adaptation of the cofactors to their special molecular environments in the
cell compartments is effected by variation of the substitution patterns of
the chromophores.
H3CO,C
CO,Phytyl
2
Heme Chlorophyll a
CONH,
CONH,
~
H,NOC
1
, CONH,
/I(Y
N~
3 4
Bacteriochlorophyll a Vitamin B"
HO
References, pp. 42-51
Naturally Occurring Cyclic Tetrapyrroles 3
Until the mid-1970s the four classic cyclic tetrapyrrolic structures
with their porphyrin, chi orin, bacteriochlorin, and corrin skeletons were
almost the only representatives in the class of porphyrinoid natural
products (1-10). Although other partially reduced porphyrins were
conceivable, none of these partially saturated porphyrinoid structures
had hitherto been found in nature.
Over the past 25 years, two developments have extended the range of
naturally occurring porphyrinoids with novel, interesting structures. The
first route of development originates from the investigation of vitamin
B12 biosynthesis (10-12). Novel hydroporphyrinoid structures have been
discovered in the search for biosynthetic intermediates leading to
vitamin BIZ' At the same time some of these structures of vitamin B12
biosynthesis were identified as cofactors of redox enzymes of micro
organisms and plants (8, 13, 14). The second route was characterized
by the deliberate search for new porphyrinoid structures in marine
organisms and micro-organisms, which resulted in the discovery of
novel porphyrinoid and hydroporphyrinoid compounds (13-18). In both
cases isolation and structural elucidation of novel structures, which often
occur as traces in natural sources, had become possible due to the
simultaneous development of new separation techniques and modem
NMR spectroscopic methods. The identification of intermediates in the
biosynthesis especially of vitamin B12 was also decisively facilitated by
application of methods from molecular biology. Last but not least the
novel structures with unusual biological activities have also attracted the
attention of organic synthetic chemists, who have developed synthetic
pathways and have thus been able to support structure elucidation, to
produce sufficient amounts of material, and to modify the natural lead
structures.
2. Classification
Due to their extended conjugated n-system, porphyrins and their
derivatives as well as corrins are deeply coloured and show characteristic
electronic absorption spectra which vary with the saturation of the
chromophoric system, with the central metal ions of the macrocycles,
and the various substituents attached to the chromophores (1, 19). Thus,
the different porphyrin derivatives can be easily distinguished from
each other. The most intense absorption of prophyrins occurs at
Amax ~ 400 nm with a molar extinction coefficient of E ~ 400000. This
band is named after its discoverer (1883) the Soret band. Other bands
with lower intensity than the Soret band occur in the long-wave length