Synthesis and antimalarial activity of some 9-substituted artemisinin derivatives
| Autor: | Robert E. Miller, Nancy Acton, James M. Karle |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
chemistry.chemical_classification
Organic peroxide Plasmodium falciparum Total synthesis Stereoisomerism Biological activity Semisynthesis Chemical synthesis Artemisinins Antimalarials Structure-Activity Relationship chemistry.chemical_compound chemistry Drug Discovery medicine Animals Molecular Medicine Organic chemistry Epimer Artemisinin Sesquiterpenes Lactone medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 36:2552-2557 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00069a014 |
| Popis: | Several 9-substituted derivatives of the antimalarial drug artemisinin have been prepared by functionalizing the double bond of artemisitene and related compounds. Stereochemical assignments for these compounds were made using a combination of NMR experiments, an X-ray diffraction study of one compound, and chemical correlations of several other compounds with this one compound of unambiguous structure and with its epimer. The compounds synthesized show a wide variation in in vitro antimalarial activity. Artemisinin, 1, and a number of its derivatives are under clinical study as antimalarial drugs by agencies such as the World Health Organization and the US. Army and by other groups both here and abroad.lV2 Artemisinin was first isolated in China, and the Chinese and others have prepared a large number of derivatives of this sesquiterpene endoperoxide. The syntheses, chemistry, and biological activity of 1 and related compounds have recently been re~iewed.3.~ Except for those prepared by total synthesis or semisynthesis, the vast majority of these derivatives involves variation at position 10, the only position in 1 subject to straightforward chemical reaction without degradation of the peroxide functionality. A number of years ago, one of us (N.A.) isolated a closely |
| Databáze: | OpenAIRE |
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