Enantioselective esterification of (R,S)-2-(4-methylphenyl) propionic acid via Novozym 435: Optimization and application

doi:10.1016/j.cjche.2019.09.003

Abstract

Abstract: This paper reports on the resolution of (R,S)-2-(4-methylphenyl) propionic acid (MPPA) enantiomers by enzymatic esterification in organic solvent. Novozym 435 (CALB) has the best catalytic performance compared with other lipases. Of the alcohols screened, n-hexanol is the best acyl acceptor and gives the highest enzyme activity and enantioselectivity in n-hexane. Response surface methodology (RSM) was used to evaluate the influence of the factors, such as temperature, enzyme amount, substrate concentration and reaction time on the substrate conversion (c) and enantiomeric excess (ee). The correlation coefficient R² for enantiomeric excess and the conversion are 0.9827 and 0.9910, respectively, indicating that can accurately predict the experimental results. By simulation and optimization, the optimal conditions were obtained, involving 600 mmol·L^-1 MPPA concentration (0.60 mmol), 850 mmol·L^-1 hexanol concentration (0.85 mmol), 58 mg enzyme amount, 75 ℃ temperature and 4.5 h reaction time, respectively. Under the optimized conditions, the experimental values of conversion and enantiomeric excess were 89.34% and 97.84%, respectively, which are in good agreement with the model predictions.

Key words: (R,S)-2-(4-Methylphenyl) propionic acid, Novozym 435, Esterification, kinetic resolution, Response surface methodology

摘要： This paper reports on the resolution of (R,S)-2-(4-methylphenyl) propionic acid (MPPA) enantiomers by enzymatic esterification in organic solvent. Novozym 435 (CALB) has the best catalytic performance compared with other lipases. Of the alcohols screened, n-hexanol is the best acyl acceptor and gives the highest enzyme activity and enantioselectivity in n-hexane. Response surface methodology (RSM) was used to evaluate the influence of the factors, such as temperature, enzyme amount, substrate concentration and reaction time on the substrate conversion (c) and enantiomeric excess (ee). The correlation coefficient R² for enantiomeric excess and the conversion are 0.9827 and 0.9910, respectively, indicating that can accurately predict the experimental results. By simulation and optimization, the optimal conditions were obtained, involving 600 mmol·L^-1 MPPA concentration (0.60 mmol), 850 mmol·L^-1 hexanol concentration (0.85 mmol), 58 mg enzyme amount, 75 ℃ temperature and 4.5 h reaction time, respectively. Under the optimized conditions, the experimental values of conversion and enantiomeric excess were 89.34% and 97.84%, respectively, which are in good agreement with the model predictions.

关键词: (R,S)-2-(4-Methylphenyl) propionic acid, Novozym 435, Esterification, kinetic resolution, Response surface methodology

Xin Yuan, Lujun Wang, Panliang Zhang, Weifeng Xu, Kewen Tang. Enantioselective esterification of (R,S)-2-(4-methylphenyl) propionic acid via Novozym 435: Optimization and application[J]. Chinese Journal of Chemical Engineering, 2020, 28(7): 1816-1823.

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