Synthesis of the Acyclic Carbon Skeleton of Filipin III.

ABSTRACT

The synthesis of the carbon skeleton of filipin III, a polyenic macrolactone possessing 11 stereogenic centers, was achieved using a convergent strategy with the longest linear sequence of 19 steps starting from hexanal. Construction of the polyene was realized using two successive Heck couplings as the key steps. Control of the stereogenic centers of the polyol fragment was performed by utilizing an Evans aldolization, a 1,3-syn aldolization, enantio- and diastereoselective allylations, a hemiacetalization/oxa-Michael sequence, and a 1,3-syn reduction. The polyol and polyenic fragments were coupled using a 1,5-anti diastereoselective aldolization followed by a 1,3-anti reduction.