Scalable Total Synthesis of Acremolactone B.

Abstract

Acremolactone B is a pyridine-containing azaphilone-type polyketide. The first total synthesis of this molecule was achieved on a gram scale, based on an aza-6π electrocyclization-aromatization strategy for construction of the tetra-substituted pyridine ring. A bicyclic intermediate was expeditiously prepared by using [2+2] photocycloaddition and chemoselective Baeyer-Villiger oxidation, which was further elaborated to a densely substituted aza-triene. An electrocyclization-aromatization cascade was utilized to forge the tetracyclic core of this natural product, and the side chain was introduced through diastereoselective acylation and reduction.