Total Synthesis of (+)-Papuamine:  An Antifungal Pentacyclic Alkaloid from a Marine Sponge, <i>Haliclona </i>sp.

Abstract

The total synthesis of (+)-papuamine, the antipode of the C(2)-symmetric, optically active, pentacyclic diamine natural product, starting from a chiral diol is described. The diol is available via an asymmetric Diels-Alder reaction between 1,3-butadiene and di-(-)-menthyl fumarate. The key transformation in the synthesis is an intramolecular Pd(0)-catalyzed (Stille) coupling reaction to form the central 13-membered diazadiene macrocyclic ring.