Total synthesis of (−)-hennoxazole A

Abstract

The antiviral marine natural product (−)-hennoxazole A was efficiently synthesized by a convergent approach. The stereoselective synthesis of the functionalized tetrahydropyran fragment was accomplished by the Mukaiyama aldol reaction, chelation-controlled 1,3- syn reduction, Wacker oxidation, and acid catalyzed intramolecular ketalization. The nonconjugated triene fragment was synthesized by S N2 displacement of an allylic bromide with vinyllithium and the CrCl 2-mediated iodoolefination followed by palladium-catalyzed cross coupling with MeMgBr. The final steps include the fragment coupling using DEPC and oxazole synthesis via an oxidation/cyclodehydration process.