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

339 Pages·1997·7.405 MB·English

by  Prof. E. Fattorusso, Prof. R. J. Highet, Dr. D. L. Klayman, Dr. A. Mangoni, Prof. R. D. H. Murray, Prof. H. Ziffer (auth.)

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72
Fortschritte der Chemie
organischer Naturstoffe
Progress in the
Chemistry of Organic
Natural Products
Founded by
L. Zechmeister
Edited by
W. Herz, G. W. Kirby,
R. E. Moore, W. Steglich,
and Ch. Tamm
Authors:
E. Fattorusso, R. J. Highet,
D. L. Klayman, A. Mangoni,
R. D. H. Murray, H. Ziffer
Springer-Verlag Wien GmbH
Prof. W. HERZ, Department of Chemistry,
The Florida State Vniversity, Tallahassee, Florida, V.S.A.
Prof. G. W. KIRBY, Chemistry Department,
The Vniversity of Glasgow, Glasgow, Scotland
Prof. R. E. MOORE, Department of Chemistry,
Vniversity of Hawaii at Manoa, Honolulu, Hawaii, V.S.A.
Prof. Dr. W. STEGLICH, Institut fiir Organische Chemie der Universităt Miinchen,
Miinchen, Federal Republic of Germany
Prof. Dr. CH. TAMM, Institut fiir Organische Chemie der Universităt Basel,
Basel, Switzerland
This work is subject to copyright.
AII rights are reserved, whether the whole or par! of the material is concemed, specifically those
of translation, reprinting, re-use of illustrations, broadcasting, reproduction by photocopying
machines or similar means, and storage in data banks.
© 1997 by Springer-Verlag Wien
Originally published by Springer-Verlag Wien New York in 1997
Softcover reprint ofthe hardcover Ist edition 1997
Library of Congress Catalog Card Number AC 39-1015
Typesetting: Thomson Press (India) Ltd., New Delhi
Graphic design: Ecke Bonk
Printed on acid-free and chlorine-free bleached paper
With 2 Figures
ISSN 0071-7886
ISBN 978-3-7091-7342-8 ISBN 978-3-7091-6527-0 (eBook)
DOI 10.1007/978-3-7091-6527-0
Contents
List of Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . X
Naturally Occurring Plant Coumarins
By R. D. H. MURRAY ......................................... .
I. Scope of the Review ....................................... 2
II. Progress in the Past Six Years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
III. Introduction to Tables ...................................... 4
Table 1. 7-0xygenated Coumarins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
1.1 6-Substituted-7-0xygenated Coumarins ............... 9
1.2 8-Substituted-7-0xygenated Coumarins ............... 15
1.3 5,6-Disubstituted-7-0xygenated Coumarins ............ 28
1.4 6,8-Disubstituted-7-0xygenated Coumarins ............ 28
Table 2. 5,7-Dioxygenated Coumarins .......................... 29
Table 3. 6,7-Dioxygenated Coumarins .......................... 40
Table 4. 7,8-Dioxygenated Coumarins .......................... 45
Table 5. 5,6,7-Trioxygenated Coumarins ........................ 48
Table 6. 5,7,8-Trioxygenated Coumarins ........................ 50
Table 7. 6,7,8-Trioxygenated Coumarins ........................ 52
Table 8. 5,6,7,8-Tetraoxygenated Coumarins . . . . . . . . . . . . . . . . . . . . .. 54
Table 9. 3-Substituted Coumarins ............................. 56
9.1 3-Aryl-Substituted Coumarins . . . . . . . . . . . . . . . . . . . . . . 58
Table 10. 4-Substituted Coumarins ............................. 59
10.1 4-Aryl-Substituted Coumarins . . . . . . . . . . . . . . . . . . . . .. 61
Table 11. Miscellaneous Coumarins . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 63
11.1 3-AryI-Oxygenated Coumarins ..................... 68
11.2 Coumestans .................................. 69
Table 12. Biscoumarins ..................................... 70
Table 13. Triscoumarins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
Amendments/Additions to Entries in Reference (171) and/or Reference [I72] .. 79
Table 1. Coumarin and 7 -Oxygenated Coumarins .................. 79
1.1 6-Substituted-7 -Oxygenated Coumarins . . . . . . . . . . . . . . .. 80
1.2 8-Substituted-7 -Oxygenated Coumarins . . . . . . . . . . . . . . .. 82
Table 2. 5,7-Dioxygenated Coumarins .......................... 85
Table 3. 6,7-Dioxygenated Coumarins .......................... 88
Table 4. 7,8-Dioxygenated Coumarins .......................... 89
VI Contents
Table 5. 5,6,7-Trioxygenated Coumarins ........................ 90
Table 6. 5,7,8-Trioxygenated Coumarins ........................ 91
Table 7. 6,7,8-Trioxygenated Coumarins ........................ 91
Table 8. 5,6,7,8-Tetraoxygenated Coumarins . . . . . . . . . . . . . . . . . . . . . . 91
Table 9. 3-Substituted Coumarins ............................. 92
9.1 3-Aryl-Substituted Coumarins . . . . . . . . . . . . . . . . . . . . . . 93
Table 10. 4-Substituted Coumarins ............................. 94
10.1 4-Aryl-Substituted Coumarins . . . . . . . . . . . . . . . . . . . . . . 95
Table 11. Miscellaneous Coumarins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
11.1 3-Aryl-Oxygenated Coumarins ..................... 97
11.2 Coumestans .................................. 97
Table 12. Biscoumarins ..................................... 98
Formula Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
Trivial Name Index ........................................... 102
References ................................................. 105
Artemisinin: An Endoperoxidic Antimalarial from Artemisia annua L.
By H. ZIFFER, R. J. HIGHET, and D. L. KLAYMAN . • • • • • • • . • • • . • . • . • • . • . •• 121
1. Introduction ............................................. 123
1.1. Historical ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 123
1.2. History of the Qinghao Plant ............................. 124
1.3. Modem History of Artemisia annua L. in Chinese Medicine ....... 125
2. Artemisia annua L. and its Constituents . . . . . . . . . . . . . . . . . . . . . . . . .. 126
2.1. Taxonomy .......................................... 126
2.2. Geographic Distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 126
2.3. Cultivation .......................................... 126
2.4. Cell Culture ......................................... 127
2.5. Isolation of Artemisinin from A. annua ...................... 127
2.6. Other Constituents of A. annua . . . . . . . . . . . . . . . . . . . . . . . . . . .. 127
3. Artemisinin Structure Determination ............................ 128
4. Artemisinin Syntheses ...................................... 129
4.1. From (-)-Isopulegol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 129
4.2. From (R)-( + )-Hydroxymenthol ........................... 131
4.3. From 3(R)-Methyl-6-phenylsulfinyl-cyc1ohexanone .............. 133
4.4. From (+ )-Isolimonene ................................. 133
4.5. From Artemisinic Acid ................................. 133
4.6. From Arteannunin B ................................... 136
5. Physical Measurements and Analyses . . . . . . . . . . . . . . . . . . . . . . . . . . .. 137
5.1. NMR.............................................. 137
5.1.1. lH .......................................... 137
5.1.2. 13C.......................................... 139
5.2. Circular Dichroism .................................... 139
5.3. Infrared ............................................ 139
5.4. Mass Spectroscopy .................................... 140
5.5. X-Ray Crystallography. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 141
Contents VII
5.6. Quantitative TLC ..................................... 141
5.7. Titrimetric .......................................... 141
5.8. HPLC 141
5.8.1. Electrochemical Detection . . . . . . . . . . . . . . . . . . . . . . . . .. 141
5.8.2. UV Detection Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142
5.8.3. Capillary Gas Chromatography ..................... . 143
5.8.4. Diverse Analytical Methods ........................ . 143
5.8.5. Radiolabelling ................................. . 143
5.8.6. Radioimmuno Assay ............................. . 143
6. Reactions of Artemisinin and its Derivatives. . . . . . . . . . . . . . . . . . . . . .. 144
6.1. Thermolysis ......................................... 144
6.2. Chemical ........................................... 145
6.2.1. Reactions with Alkali ............................. 145
6.2.2. Reactions with Ammonia and Amines ................. 146
6.2.3. Reactions with Acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 148
6.2.3.1. Arteether . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 148
6.2.3.2. Dihydroartemisinin ......................... 149
6.2.3.3. Acid-Catalyzed Additions to Anhydro-
dihydroartemisinin ......................... 150
6.2.3.3.1. Triphenylphosphine Hydrobromide . . . . . .. 150
6.2.3.3.2. p-Toluenesulfonic Acid. . . . . . . . . . . . . .. 150
6.2.3.4. Acid-Catalyzed Rearrangements of Artemisinin
Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 150
6.2.3.4.1. Lewis Acids. . . . . . . . . . . . . . . . . . . . . .. 150
6.2.3.4.2. Silica Gel-Catalyzed Rearrangements ..... 150
6.2.4. Reaction of Artemisinin with Reducing Agents ........... 153
6.2.4.1. Lithium Aluminum Hydride. . . . . . . . . . . . . . . . . .. 153
6.2.4.2. Sodium Borohydride . . . . . . . . . . . . . . . . . . . . . . .. 153
6.2.4.3. A Mixture of Sodium Borohydride and
Boron Trifluoride .......................... 153
6.2.4.4. Hydrogenation ............................ 154
6.2.5. Bromination.................................... 155
6.2.6. Fluorinated Artemisinin Derivatives ................... 155
6.2.7. Epoxidation of Anhydrodihydroartemisinin .............. 156
6.2.8. Osmium Tetroxide Oxidation . . . . . . . . . . . . . . . . . . . . . . .. 157
7. Dihydroartemisinin Derivatives ................................ 158
7.1. Derivatives with Enhanced Oil Solubility . . . . . . . . . . . . . . . . . . . .. 158
7.1.1. Ethers........................................ 158
7.1.2. Esters ........................................ 159
7.1.3. Carbonates..................................... 159
7.2. Derivatives with Enhanced Water Solubility . . . . . . . . . . . . . . . . . .. 160
7.2.1. Sodium Artesunate .. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 160
7.2.2. Sodium Artelinate and Related Derivatives .............. 160
7.3. Artemisinin Derivatives ................................. 161
7.3.1. (+ )-Deoxoartemisinin . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 161
7.3.2. (+)-Homodeoxoartemisinin .. . . . . . . . . . . . . . . . . . . . . . .. 162
7.3.3. (+)-lO-Alkyldeoxoartemisinin ....................... 163
7.3.4. (+)-lO~-Allyldeoxoartemisinin ...................... 164
VIII Contents
7.3.5. C-3 and C-9 Substituted lO-Deoxoartemisinins ........... 164
7.3.6. C-14 Modified Deoxoartemisinins .................... 165
8. Simplified Artemisinin Derivatives. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 166
8.1. 9-Desmethylartemisinin ................................. 166
8.2. 6,9-Bisnorartemisinin................................... 166
8.3. (+ )-8a,9-Secoartemisinin ................................ 167
8.4. (+ )-4,5-Secoartemisinin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 168
8.5. (+ )-Hexabydroisochroman-3-one . . . . . . . . . . . . . . . . . . . . . . . . . .. 170
8.6. 4,5-Desethanoartemisinin ................................ 170
8.7. 9-Alkyl-9-desmethylartemisinin............................ 170
8.8. C-3 and C-9 Modified Artemisinin Derivatives ................. 171
8.9. Carba-Analogs of Artemisinin ............................ 172
9. Quantitative Structure-Activity Analyses. . . . . . . . . . . . . . . . . . . . . . . . .. 173
10. Tricyclic 1,2,4-Trioxane Analogs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 174
11. Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 175
11.1. Microbial Metabolites of Artemisinin and its Derivatives. . . . . . . . .. 175
11.2. Mammalian Metabolites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 177
12. Test Data of Artemisinin Derivatives ............................ 178
12.1. In Vitro ............................................ 178
12.2. In Vivo. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 188
13. Toxicity ................................................ 193
14. Pharmacology and Pharmacokinetics ............................ 194
15. Clinical Evaluation of Artemisinin and Derivatives .................. 195
15.1. Dihydroartemisinin .................................... 196
16. Mechanisms of Action .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 196
17. Other Peroxides. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 198
17.1. Naturally Occurring Peroxides ............................ 198
17.2. Synthetic Peroxides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 199
18. Conclusion .............................................. 201
References ................................................. 202
Marine Glycolipids
By E. FATTORUSSO and A. MANGONI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 215
1. Introduction ............................................. 215
2. Isolation Procedures ....................................... 218
3. Determination of the Structure of Glycolipids . . . . . . . . . . . . . . . . . . . . .. 219
3.1. Determination of the Structure of the Sugar Portion ............. 220
3.2. Determination of the Structure of the Lipid Portion ............. 222
4. Glycoglycerolipids 223
5. Glycosphingolipids ........................................ 228
5.1. Neutral Glycosphingolipids .............................. 229
Contents IX
5.2. Phosphorus-Containing G\ycosphingolipids ................... 247
5.3. Gangliosides......................................... 260
6. Other Glycolipids ......................................... 281
7. Biological Activities ....................................... 287
7.1. Immunological Activity ................................. 287
7.2. Pharmacological Activity .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 288
References ................................................. 291
Author Index ..... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 303
Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 319
List of Contributors
FATTORUSSO, Prof. E., Dipartimento di Chimica delle Sostanze Naturali, Facolta di
Farmacia, Universita degli Studi di Napoli Federico II, Via Domenico Montesano 49,
1-80 131 Napoli, Italy
HIGHET, Prof. R. J., Laboratory of Biophysical Chemistry, National Heart, Lung and Blood
Institute, National Institutes of Health, Bethesda, MD 20892, U.S.A.
KLAYMAN, Dr. D. L., Walter Reed Army Institute of Research, Division of Experimental
Therapeutics, Washington, DC 20307, U.S.A.
MANGONI, Dr. A., Dipartimento di Chimica delle Sostanze Naturali, Facolta di Farmacia,
Universita degli Studi Napoli Federico II, Via Domenico Montesano 49, I-80l3l Napoli,
Italy
MURRAY, Prof. R. D. H., "Selsey", 25 Haugh Road, Dalbeattie DG5 4AR, Scotland
ZIFFER, Prof. H., Laboratory of Chemical Physics, National Institute of Diabetes, Digestive
and Kidney Diseases, National Institutes of Health, Bldg. 5, Room B 1-31, Bethesda, MD
20892-0510, U.S.A.
Naturally Occurring Plant Coumarins
R. D. H. MURRAY
Chemistry Department, University of Glasgow,
Glasgow G 12 8QQ, Scotland
Contents
I. Scope of the Review. . . . . . . 2
II. Progress in the Past Six Years. 3
III. Introduction to Tables. . . . . 4
Table 1. 7-0xygenated Coumarins 6
1.1 6-Substituted-7-0xygenated Coumarins 9
1.2 8-Substituted-7-0xygenated Coumarins 15
1.3 5,6-Disubstituted-7-0xygenated Coumarins 28
1.4 6,8-Disubstituted-7-0xygenated Coumarins 28
Table 2. 5,7-Dioxygenated Coumarins 29
Table 3. 6,7-Dioxygenated Coumarins . . 40
Table 4. 7,8-Dioxygenated Coumarins . . 45
Table 5. 5,6,7-Trioxygenated Coumarins 48
Table 6. 5,7,8-Trioxygenated Coumarins 50
Table 7. 6,7,8-Trioxygenated Coumarins 52
Table 8. 5,6,7,8-Tetraoxygenated Coumarins 54
Table 9. 3-Substituted Coumarins ..... 56
9.1 3-Aryl-Substituted Coumarins 58
Table 10. 4-Substituted Coumarins ..... 59
10.1 4-Aryl-Substituted Coumarins . 61
Table 11. Miscellaneous Coumarins . . . . . . 63
11.1 3-Aryl-Oxygenated Coumarins 68
11.2 Coumestans 69
Table 12. Biscoumarins 70
Table 13. Triscoumarins . . 78
Amendments/Additions to Entries in Reference (171) and/or Reference [172] . 79
Table 1. Coumarin and 7-0xygenated Coumarins 79
1.1 6-Substituted-7-0xygenated Coumarins 80
1.2 8-Substituted-7-0xygenated Coumarins 82
Table 2. 5,7-Dioxygenated Coumarins ........ 85