Total Synthesis of (-)-Enigmazole A by the Macrocyclization/Transannular Pyran Cyclization Strategy.

An 18-step synthesis of (-)-enigmazole A is herein disclosed. The present synthesis is based on a modular assembly of three building blocks of similar complexity, a macrocyclic ring-closing metathesis to forge the 18-membered macrocyclic skeleton, and a desilylative transannular oxa-Michael addition for stereoselective construction of the 2,6- cis -substituted tetrahydropyran ring.