Scalable Total Synthesis of Acremolactone B

Abstract

Acremolactone B is a pyridine‐containing azaphilone‐type polyketide with herbicidal activity. We developed an aza‐6π electrocyclization−aromatization strategy to construct the tetrasubstituted pyridine ring and achieved the first total synthesis of this molecule on a gram scale. 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 exploited to forge the tetracyclic core of the natural product, and the side chain was introduced through diastereoselective acylation and reduction.