The discovery of new reactions will facilitate the development of new drug entities and promising new therapeutics. This proposal will seek to apply novel chiral organic salts to catalyze the formation of carbon-carbon bonds possessing stereochemistry at both ends of the bond. Stereochemically dense functionality is associated with improved specificity for one target. The research plan involves the use of tri- and tetra-substituted Michael acceptors with tethered aldehydes in an asymmetric Stetter reaction. Reversing the normal reactivity of aldehydes as electrophiles to make them function as nucleophiles is one of the tenets of this research. Successful realization of these goals will allow us to use the chemistry developed to facilitate a rapid synthesis of azaspirene, a potent angiogenesis inhibitor, a strategy of significant interest in cancer chemotherapy. It is envisioned, however, that the broader impact of this science may be in revealing a new reaction manifold and a novel strategy to solving problems of molecular complexity particularly relevant to synthetic approaches to pharmaceutical targets. ? ?
