A first generation total synthesis of (+)-salicylihalamide A

Abstract

An efficient total synthesis of (+)-salicylihalamide (1) is described. The synthetic strategy features a highly E-selective ring-closing metathesis to construct the 12-membered salicylihalamide A macrocycle and a practical method for installation of the labile ene-hepta-(Z,Z)-dienamide side chain, which relies on a Curtius rearrangement to forge the C18-N bond with subsequent N-acylation.