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.