UC Santa Barbara

The total synthesis of (–)-lycopodine, a member of the Lycopodium alkaloid family, has been a longstanding challenge in synthetic organic chemistry, with many previous efforts yielding primarily racemic mixtures. In this thesis, I present a novel synthetic approach that introduces a chiral center at the very first step, thereby steering the synthesis towards enantioselectivity from the outset. A key feature of our methodology is an unprecedented Grignard addition, which plays a critical role in constructing the core framework of (–)-lycopodine. Our synthesis has progressed to an advanced intermediate, positioned just one step away from the final product. This work represents a significant advance in the stereocontrolled synthesis of Lycopodium alkaloids, providing new insights and strategies for the total synthesis of complex natural products.