Enantioselective lipase-catalyzed acetylation of beta-lactam precursors ofcarbapenem antibiotics

The Amano PS-lipase-catalyzed enantioselective acetylation in vinyl acetate of (+/-)-3-hydroxyethyl-beta-lactams 3-6, useful precursors of carbapenem antibiotics, proceeds with high enantioselectivity (E > 98) to afford the c orresponding acetates 3b-6b in optically pure form. The rate of acetylation is influenced by the relative stereochemistry of the C(3)-C(4) beta-lactam carbon atoms, the trans isomers being transformed much faster than the cis ones. The stereochemical preference of the lipase-PS is for the (1'R,3R) e nantiomers, as determined by chemical correlation. On the other hand, the l ipase-PS-catalyzed hydrolysis of esters 3b,d in phosphate buffer proceeds w ith low selectivity and at a lower rate.