A General Strategy for the Synthesis of Jerangolids Enabled by π‐allyl Stille Coupling

Jerangolids are polyketide natural products with potent antifungal activity and low mammalian toxicity, originally isolated from Sorangium cellulosum So ce 307. Their structure, consisting of a δ-lactone and a pyran unit connected by a chiral skipped 1,4-diene, presents a significant synthetic challenge. Herein, we describe a general, modular strategy that enables the synthesis of all naturally occurring jerangolids and their stereoisomers, including the still elusive jerangolid H. The lactone fragment was built through a vinylogous Mukaiyama aldol reaction, with the hydroxymethyl group at C2 introduced in one step by Stille coupling with a novel p-methoxybenzyloxymethyl (PMBM) stannatrane. The stereocenter at both C14 and C15 was generated via deoxygenation of a tertiary alcohol involving a [1,2]-H-shift. Using a highly modular approach recently developed by our group, the jerangolid framework was assembled in a single step through enantioselective π-allyl Stille coupling of the two key fragments. Synthesis and comparison of both C14 epimers allowed us to unambiguously establish the total configuration of jerangolid H.