Enantioselective lipase-catalyzed acetylation of β-lactam precursors of carbapenem antibiotics

Abstract

The Amano PS-lipase-catalyzed enantioselective acetylation in vinyl acetate of (±)-3-hydroxyethyl-β-lactams 3–6, useful precursors of carbapenem antibiotics, proceeds with high enantioselectivity (E > 98) to afford the corresponding acetates 3b–6b in optically pure form. The rate of acetylation is influenced by the relative stereochemistry of the C(3)–C(4) β-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) enantiomers, as determined by chemical correlation. On the other hand, the lipase-PS-catalyzed hydrolysis of esters 3b,d in phosphate buffer proceeds with low selectivity and at a lower rate.