A Concise and Unified Strategy for Synthesis of the C1–C18 Macrolactone Fragments of FD-891, FD-892 and Their Analogues: Formal Total Synthesis of FD-891

Abstract

A concise and unified strategy for the synthesis of C1–C18 macrolactone fragments of FD-891 and FD-892 as well as their analogues is reported. The strategy includes a stereoselective vinylogous Mukaiyama aldol reaction (VMAR) using chiral silyl ketene <i>N,O</i>-acetal to construct C6–C7 stereocenters, an <i>E</i>-selective ring closing metathesis to construct a C12–C13 olefin, and stereodivergent construction of a C8–C9 epoxide