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, relevant, and selective chemical methodology to drive the 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 catalytic, stereoselective reactions that facilitate the efficient construction of heterocyclic targets. The new methods advanced in this proposal have a) significant and highly encouraging preliminary results, and b) been inspired by natural products that will subsequently facilitate the efficient construction of these targets and potential applications towards clinical endpoints. The innovative catalytic tactics we are pursuing should facilitate investigations of biological processes relevant to the discovery of new potential therapies and strategies that generate the targeted natural products structures while providing broad solutions to synthesizing related families of compounds. The specific goals of this research are: a) the exploration of new, stereoselective catalytic carbocation-driven transformations, b) the exploration of new calcium-catalyzed amine conjugate additions, and c) the development of Lewis acid-catalyzed ?-Umpolung type radical reactions. 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.
This research program aims to continue the successful development of efficient synthesis of biologically active small molecules and natural products possessing stereochemically rich heterocycles through the development and subsequent application of new Lewis/Brnsted acid-catalyzed methods for organic synthesis. We are specifically investigating innovative Lewis acid strategies combined with catalytic asymmetric methods to generate, control and utilize reactive electron deficient species to produce high value, chiral heterocycles. Synthesis is a primary activity to drive an understanding of mechanism of action and to develop new chemical probes and potential therapeutics from natural product sources, which is critical for new knowledge and medical advances.
