Title: Synthetic Innovations Towards the Total Synthesis of Natural Product Derivatives for Drug Development
Description: In order to provide scalable, efficient and selective routes towards pharmaceutically relevant compounds, we have focused on improving the economical viability and practicality of strained-silane Lewis acid activation. Towards these goals, the Leighton group has developed a new mode of anion catalysis to activate silane Lewis acids. Weakly coordinating anions have been used to access hyper-coordinate silicon species with unprecedented levels of reactivity, which have facilitated previously unattainable complex fragment couplings. A highly enantioselective and efficient method for anion catalyzed nucleophilic addition to aldehydes has enabled the synthesis of rationally designed, structurally simplified D-ring modified analogs of spongistatin 1. The completion of a step-economical route towards extremely potent, linker-handle equipped spongistatin 1 analogs and their application to targeted drug delivery will be discussed.