This proposal focuses on the synthesis of antineoplastic agents. In the quassinoid area major emphasis will be placed on completing syntheses of quassimarin, bruceantin, and glaucarubinone. As a result of the lower toxicity in in vivo systems of 4beta-hydroxy withanolide E relative to cardenolides and bufadienolides, a synthetic program centered around 4beta-hydroxy withanolide E has been initiated in an effort to uncover an analog possessing a reasonable therapeutic index. Part III of this proposal focuses on a convergent total synthesis of the potent cytotoxic cyclodepsidpeptide, jaspamide. In addition a number of analogs will be prepared in order to examine the structural requirements for biological activity.
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