The proposed research project will provide an effective training program for graduate students aspiring to careers in the area of organic synthesis for application to biomedical problems while achieving the following important aims: 1) the synthesis of the structurally unique antileukemic bluegreen algal metabolites oscillatoxin D and 30-methyloscillatoxin D, 2) investigations of novel stereoselective methods for organic synthesis, including Lewis acid or palladium mediated ring closures, for selectively assembling the unprecedented 1-oxa-[5.5]-spirobicycloundec-4-ene-8-one ring system of oscillatoxin D, 3) the exploration of the production of a hypothetical activated diene derivative of the """"""""D"""""""" oscillatoxins which would have alkylating activity relevant to biological activity, and 4) the submission of the synthetic """"""""D"""""""" oscillatoxins, synthetic intermediates, and structurally related analogues --- available in significant quantities for the first time by the proposed syntheses - -- for biological evaluation for antibacterial, antiviral, antifungal, antiparasitic and antineoplastic activity. The proposed three-year project will lead to important new knowledge about the construction and biological activity of spirocyclic molecules. Better understanding of the chemistry of allypalladium complexes, dihydropyrans and spirobicyclic polyfunctionalized arrays will result, and novel insights into remote """"""""vinylogous"""""""" stereoelectronic effects are anticipated. Furthermore, the discovery of novel and significant biologically active agents having potential therapeutic applications will result from the project.
