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

The total synthesis of (+)-papuamine, the antipode of the C₂-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.