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.