Unified Approach to Indolosesquiterpene Alkaloids: Total Syntheses of Anti-Viral Agents, Xiamycin A and Oridamycin A

Abstract

A unified catalytic asymmetric total synthesis of naturally occurring anti-viral indolosesquiterpene alkaloids, xiamycin A (1a) and oridamycin A (2a) has been accomplished. The In(III)-catalyzed regio- and diastereoselective ene-yne cyclization has been utilized to construct the pentacyclic skeleton 6 (>20:1 dr) having an exocyclic olefin. Diastereoselective hydroboration oxidation afforded the advanced intermediate b-hydroxy aldehyde 5a. Finally, a late-stage highly diastereoselective methylation followed by stereocenter adjustment completed the total syntheses of xiamycin A (1a) and oridamycin A (2a).