Kinetic modeling and statistical optimization of lipase catalyzed enantioselective resolution of (R,S)-2-pentanol

Abstract

S-2-pentanol is a chiral intermediate in the synthesis of several potential antialzheimer’s drugs that inhibit β-amyloid peptide release or its synthesis. The present work focuses on the kinetic resolution of (R,S)-2-pentanol using vinyl acetate as an acyl donor. Effects of various parameters were studied to deduce the kinetics and mechanism of the reaction. Novozyme 435 was found to be the most efficient catalyst among different catalysts studied. Response Surface methodology and Box–Behnken design were employed to evaluate the effect of process parameters such as speed of agitation, enzyme loading, temperature and acyl donor/alcohol molar ratio on conversion, enantiomeric excess, enantioselectivity and initial rate. Initial rate data and progress curve data were used to arrive at a suitable model. Ping–pong bi–bi mechanism with 2-pentanol inhibition was found to describe the kinetics of the reaction. The kinetic parameters evaluated from initial rate data were used to simulate the experimental results. There was a very good agreement between theory and experiment.