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 BoxÀBehnken 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. PingÀpong biÀbi 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.

BACKGROUND: Optically pure amines are used in the fine chemical industry as resolving agents, chiral auxiliaries, and chiral synthetic building blocks for pharmaceuticals as well as agrochemicals. Lipase-catalyzed kinetic resolution of (±)-1-phenylethylamine with ethyl acetate as an acyl donor was achieved using immobilized lipase (Novozyme 435) as a biocatalyst under microwave irradiation.

Optically active 1-phenylethanol is used as a chiral building block and synthetic intermediate in pharmaceutical and fine-chemical industries. Lipase - catalyzed kinetic resolution of (R,S)-1-phenylethanol with vinyl acetate as an acyl donor and Candida antarctica immobilized lipase as a biocatalyst in a batch reactor was optimized using Response Surface Methodology (RSM). Four-factor-five-level central composite rotatable design (CCRD) was employed to evaluate the effect of synthesis parameters such as speed of agitation, enzyme loading, temperature and acyl donor/alcohol molar ratio, on conversion, enantiomeric excess (ee), enantioselectivity and initial rate. Optimum reaction conditions obtained were; mole ratio of acyl donor: ester of 2:1, temperature of 42.5 °C, catalyst loading of 1.6x10-3 g.cm-3 and speed of agitation of 336 rpm. Analysis of variance was performed to determine significantly affecting variables and interactions between the process parameters.

Chiral 2-octanol is one of the key intermediates for preparation of liquid crystal materials, as well as many optically active pharmaceuticals. Lipase catalyzed kinetic resolution has proved to be an efficient technique for synthesis of enantiomerically enriched compounds. In the present study, optimization and kinetic modeling of kinetic resolution of (±)-2-octanol was done by using vinyl acetate as an acyl donor in n-heptane as a solvent. Response surface methodology (RSM) and four-factor-five-level Centre Composite Rotatable Design (CCRD) were employed to evaluate the effect of various parameters such as speed of agitation, enzyme loading, temperature and acyl donor/alcohol molar ratio on conversion, enantiomeric excess (ee), enantioselectivity and initial rate of reaction. Acylation of 2octanol with vinyl acetate catalyzed by Novozyme 435 follows the ternary complex mechanism (ordered bi-bi mechanism) with inhibition by 2octanol.

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