Synthesis of Dysoxylactam A Using Iterative Homologation of Boronic Esters

Abstract

Dysoxylactam A is a 17-membered macrocyclic lipid which has been found to dramatically reverse multidrug resistance in cancer cells. Three previous syntheses have been reported in 15–17 steps. Using iterative lithiation-borylation reactions as the key C−C bond forming and stereocontrolling steps, we now describe an 11-step synthesis of dysoxylactam A. The complete sequence only required a total of five chromatographic purifications and used minimal protecting groups making it both rapid and efficient.