The study first reported the efficient lipase catalysis of aza-Markovnikov addition of N-heterocycles to vinyl esters in organic media. After screening the enzyme sources and organic solvents, the yield was up to 82.6% and the reaction rate increased more than 600-folds under the catalysis of Amino lipase M from Mucor javanicus in DMSO. Some control experiments were designed to demonstrate the catalytic specificity of lipase. A new strategy for the enzymatic synthesis of drug derivatives was developed by combining aza-Markovnikov addition with acylation procedure involving divinyl esters as linkers. A series of drug derivatives containing N-heterocycles were successfully obtained. The new activity of lipase expands the application of biocatalyst and provides a useful avenue to synthesize drug derivatives. (c) 2008 Elsevier Inc. All rights reserved.