Total Synthesis and Structural Confirmation of (+)-Longicin

Abstract

A stereocontrolled total synthesis of (+)-longicin, a representative of the class of mono-THF-acetogenins, is described. The strategy involves the utilization of d- and l-glutamic acids as chirons that correspond to two five-carbon segments harboring stereogenic centers at C4 and at C17 of the C(32) polyketide-derived natural product. The use of Grubbs' RCM reaction as a novel "chain elongation" strategy for the synthesis of acetogenin-type structures and a new protocol for butenolide incorporation are also described. [structure: see text]