Stereoselective acetylation of [1-(hydroxy)-4-(3-phenyl)butyl]phosphonic acid, diethyl ester

The chiral intermediate (S) [1-(acetoxyl)-4-(3-phenyl)butyl]phosphonic acid, diethyl ester 2 was prepared for the total synthesis of a squalene synthase inhibitor, BMS-188494. The stereoselective acetylation of racemic [1-(hydroxy)-4-(3-phenyl)butyl] phosphonic acid, diethyl ester 1 was carried out in toluene using lipase from Geotrichum candidum. Isopropenyl acetate was used as an acylating agent. A reaction yield of 38% and an optical purity of 95% were obtained for chiral 2.