The total synthesis of endolides A and B has been achieved in a concise, highly stereoselective fashion (12 steps, 16.2% and 16.0% overall yields, respectively). Key features of the route include a modified Negishi coupling between 3-bromofuran and an organozinc reagent derived from an iodoalanine derivative for the synthesis of 3-(3-furyl)-alanine derivative, and a judicious choice of reaction conditions to surmount the conformational constraints placed by converting a linear peptide into the corresponding macrocycle.
Keywords: 3-(3-furyl)-alanine; Buchwald phosphine ligands; Negishi coupling; endolides; total synthesis.