Stereoselective Synthesis of the Macrolactone Core of (+)-Neopeltolide

Abstract

A stereoselective synthesis of the macrolactone core of the potent anticancer agent neopeltolide is disclosed. The key steps of the synthesis include asymmetric allylation using Krische’ protocol, conjugate reduction using MacMillan’s methodology, and an asymmetric hetero-Diels–Alder reaction using Jacobsen’s catalyst. Substrate controlled diastereoselective 1,3-<i>anti</i> reduction of a keto alcohol, Luche reduction followed by Ireland–Claisen rearrangement, oxymercuration, and reductive lithiation are other key steps