Optimization of the asymmetric synthesis of chiral aromatic alcohol using freeze-dried carrots as whole-cell biocatalysts

Abstract

Asymmetric reduction of ketones is an important transformation in organic synthesis, because chiral carbinols are useful bioactive compounds. In this study, bioreduction of acetophenone (ACP) for production of enantiomerically pure (S)-1-phenyl-ethanol was investigated and freeze-dried carrots were used as a source of alcohol dehydrogenases (ADHs). However, production of product was investigated systematically using response surface methodology (RSM). Before RSM, the effects of the initial substrate concentration, reaction time, temperature and pH on the bioreduction were studied. The best results for enantiomeric excesses (ee) and conversion (c) were obtained with >99% and 58%, respectively, for the reaction time 48 h, initial substrate concentration 1 mm, reaction temperature 33°C and pH 7. In the RSM, initial substrate concentration, concentration of plant cell, reaction time and stirring rate were chosen as independent variables. The predicted optimum conditions for a higher ee (>99%) and conversion (57.8%) were as follows: initial substrate concentration, 1 mm; concentration of plant cell, 25 g/l; reaction time, 52 h and stirring rate, 200 rpm. As a result of repeated experiments, the product was obtained as 0.6 mm at this optimum point and the values obtained demonstrated conformity with 0.578 mm value calculated by the model equation.

Keywords

• acetophenone
• asymmetric reduction
• biocatalyst
• optimization
• (s)-1-phenyl-ethanol