A Global and Local Desymmetrization Approach to the Synthesis of Steroidal Alkaloids: Stereocontrolled Total Synthesis of Paspaline

A stereocontrolled total synthesis of the indole diterpenoid natural product paspaline is described. Key steps include a highly diastereoselective enzymatic desymmetrization, substrate-directed epoxidation, Ireland-Claisen rearrangement, and diastereotopic group selective C–H acetoxylation to assemble the target with excellent stereofidelity. The route and results described herein outline complementary conceptual disconnections in the arena of steroid natural product synthesis.