Stereoselective Total Synthesis of Nimbolide

Abstract

A stereoselective total synthesis of nimbolide has been achieved in a convergent, 11-step sequence from α-methyl-( R )-carvone. The strategy relied on a stereoselective palladium-catalyzed borylative Heck cyclization where the A-ring of the nimbolide core was constructed while simultaneously performing oxidation at C(28). Selective manipulations delivered a fully decorated decalin moiety on large scale. Then, a stereoretentive etherification reaction brought together two fragments and forged the critical C–O bond with high selectivity. Finally, a regioselective radical cyclization and late-stage lactonization completed the total synthesis of nimbolide.

Topics & Concepts