Total Synthesis of (‒)-Deglycocadambine

Abstract

The first total synthesis of monoterpene indole alkaloid (–)-deglycocadambine is achieved in 12 steps with (+)-genipin as the chiral starting material. The reported synthetic approach is characterized with the orchestrated cascade annulation between tryptamine and the highly functionalized dialdehyde precursor to rapidly introduce the unique 6/5/6/7/6-fused pentacyclic skeleton and the functional group ketone at C19 in a convergent manner. The successful implementation of the transannular oxidative cyclization at C3 for the bridged oxazolidine formation in the late-stage synthetic campaign ensured the final total synthesis of this molecule.