Cardenolide structural studies

The present volume reflects these developments, and there is a growing emphasis on bioactive natural products. Articles in this volume include those on structure-activity relationships of highly sweet natural products, chemical constituents of cchinodenns, diterpenoids from Rabdosia and Eremophila sp., structural studies on saponins, marine sesquiterpene quinoncs and antimicrobial activity of amphibian venoms. The reviews on bioactive metabolites of Phomopsis, cardenolide detection by ELISA, xenocoumacins and bioactive dihydroisocoumarins, CD studies of carbohydrate-molybdate complexes, oncogene function inhibitors from microbial secondary metabolites and Gelsemium and Lupin alkaloids present frontier developments in several areas of natural product chemistry. It is hoped that the present volume, which contains articles by eminent authorities in each field, will be received with the same enthusiasm as the previous volumes of this series. 

An isomeric sugar, D-javose, is a constituent of two cardenolide glycosides (strophanthojavoside and antiarojavoside) found (42) in the seeds of Antiaris toxicaria Lesch. Degradative studies indicated (42) that javose had the structure 6-deoxy-2-0-methyl-D-allose (17) and this assignment was confirmed by two stereospecific syntheses. 

Practically all of the known cardenolides have been assayed by Chen and his coworkers the data were obtained in one laboratory under conditions as nearly identical as possible. It is for this reason that meaningful results can best be obtained from this method, particularly for comparison studies in terms of structure-activity relationships. Also, it is important to note that the potency figures for cats are applicable to man, when the drugs are administered intravenously. The data cited in Table I are all Chen assay values those obtained prior to 1961 may be found in an excellent compilation by Hoch.1 Cardenolides, for which assay figures have since been given by Chen, will be referenced accordingly. 

As the outcome of the aforementioned studies, the shortest known asymmetric approach to the cardenolides skeleton was developed." Complex steroids with natural (26) and unnatural (24) craifiguration can be generated in only four to five steps from the conunercially available starting materials. The craiciseness of this approach allows a rapid generation of structurally diverse analogs, some of which are not easily accessible via a traditional semis)mihetic approach. 

Recent studies on Asclepias curassavica [197], and Bersama abyssinica [198, 199] have shown that bufadienolides and cardenolides are cytotoxic and that hellebrigenin 3-acetate (XLIX) inhibits W 256 at 8 mg/kg. Structure-activity relationship studies on bufadienolides and cardenolides have failed to reveal the structural features required for activity [194]. 

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