(Principal Investigator's) The long term objectives of this program include the laboratory synthesis of complex natural products possessin desirable biological activity as well as the development of new synthetic methodology which will simplify this task. Specific natural products to be studied include the promising antitumor agent rhizoxin, structurally simplifie analogues of rhizoxin, and the highly cytotoxic marine natural product swinholide as well as misakinolide and scytophycin C, both of which are structurally very similar to swinholide. In addition, studies directed at tota syntheses of epothilone A & B and bryostatin 1 will be initiated. The epothilones are exciting new agents with biological activity very similar to taxol, and are thus important new structures of relevance to cancer chemotherapy. The potent new immunosuppressive agent pironetin will also be synthesized. The main thrust of the program, from a chemical point of view, is to develop new strategies and reactions which simplify the synthesis of these materials. An important focus of this research is the development of catalytic asymmetric reactions which allow for the formation of new stereogenic centers via union of two sp2 centers in a manner controlled by the catalyst.
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