New Cooperative Catalysis Concepts for Asymmetric Synthesis

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Project Summary Advances in 21st century medicine have greatly impacted society, but a serious need persists for new therapeutics that either exploit known biological processes or possess novel mechanisms of action. The development of new, selective, and enabling chemical methodology to drive the rapid investigation of the reactivity and biological activity of natural products and related probes is vital to understanding their mechanism of action and developing new therapeutics for the treatment and/or prevention of disease. A primary goal of our research program is to discover and develop new cooperative catalytic, stereoselective transformations that facilitate the highly efficient construction of valuable materials. The new methods advanced in this proposal have a) significant and highly encouraging preliminary results, and b) been inspired by bioactive molecules/natural products that will subsequently facilitate the efficient construction of these targets and potential applications towards clinical endpoints. The innovative cooperative catalytic strategies we are pursuing will power investigations of biological processes relevant to the discovery of new potential therapies and strategies that generate the targeted bioactive molecules while providing broad solutions to synthesizing related families of compounds. The specific goals of this research are: a) the exploration of new, cooperative carbene catalyzed processes, b) the development of stereoselective catalytic carbocation-driven transformations, c) the investigation of Lewis acid-catalyzed -Umpolung type radical reactions, and d) the merger of photocatalytically-generated reactivity with biocatalysis. We anticipate that these research activities will fundamentally advance human health by providing innovative tactics and strategies to access many important classes of health relevant compounds.