Synthetic studies on bafilomycin A1: stereoselective synthesis of the C12–C17 fragment and its coupling with the C1–C11 subunit

Stereoselective addition of (E)-1-lithio-2-tributylstannylethylene on a chiral cyclic di-t-butylsilyleneketal C14–C17 aldehyde afforded the required Felkin–Anh adduct for the synthesis of the C12–C17 fragment of bafilomycin A1, the configuration of which was assigned unambiguously. After appropriate coupling with the enantiopure C1–C11 fragment, the C12–C17 subunit obtained here can be used for the study of the 16-membered macrolide formation either by an acyl activation or an intramolecular Stille reaction. Intermolecular esterification of the 15-OH with an acyl activation of the carboxylic acid of the C1–C11 fragment, in modified Yamaguchiʹs conditions, affords here an intermediate for examining an intramolecular Stille coupling.