Total Synthesis of (+)-Ansatrienol K

Abstract

The first total synthesis of ansatrienol K, a novel trienomycin congener featuring a diene moiety within its 19-membered macrolactam ring, is reported. Key steps include two sequential palladium-catalyzed cross-coupling reactions for constructing the trisubstituted benzene ring and two distinct strategies for assembling the C6–C18 fragment. A Co₂(CO)₈-catalyzed carbonylative epoxide ring-opening provided the diene fragment, while late-stage Stewart–Grubbs catalyst-mediated diene-ene ring-closing metathesis (RCM) enabled efficient macrocyclization.