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KMID : 0545120130230030343
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Journal of Microbiology and Biotechnology
2013 Volume.23 No. 3 p.343 ~ p.350
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Efficient Enantioselective Synthesis of (R)-[3,5-Bis(trifluoromethyl)phenyl] Ethanol by Leifsonia xyli CCTCC M 2010241 Using Isopropanol as Co-Substrate
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Qi Ouyang
Pu Wang
Jin Huang
Jinbo Cai
Junyao He
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Abstract
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(R)-[3,5-Bis(trifluoromethyl)phenyl] ethanol is a key chiral intermediate for the synthesis of aprepitant. In this paper, an efficient synthetic process for (R)-[3,5- bis(trifluoromethyl)phenyl] ethanol was developed via the asymmetric reduction of 3,5-bis(trifluoromethyl) acetophenone, catalyzed by Leifsonia xyli CCTCC M 2010241 cells using isopropanol as the co-substrate for cofactor recycling. Firstly, the substrate and product solubility and cell membrane permeability of biocatalysts were evaluated with different co-substrate additions into the reaction system, in which isopropanol manifested as the best hydrogen donor of coupled NADH regeneration during the bioreduction of 3,5-bis(trifluoromethyl) acetophenone. Subsequently, the optimization of parameters for the bioreduction were undertaken to improve the effectiveness of the process. The determined efficient reaction system contained 200mM of 3,5-bis(trifluoromethyl) acetophenone, 20% (v/v) of isopropanol, and 300 g/l of wet cells. The bioreduction was executed at 30oC and 200 rpm for 30 h, and 91.8% of product yield with 99.9% of enantiometric excess (e.e.) was obtained. The established bioreduction reaction system could tolerate higher substrate concentrations of 3,5- bis(trifluoromethyl) acetophenone, and afforded a satisfactory yield and excellent product e.e. for the desired (R)-chiral alcohol, thus providing an alternative to the chemical synthesis of (R)-[3,5-bis(trifluoromethyl)phenyl] ethanol.
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KEYWORD
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Leifsonia xyli, enantioselective reduction, 3, 5-bis(trifluoromethyl) acetophenone, (R)-[3, 5-bis(trifluoromethyl)phenyl] ethanol, co-enzyme regeneration
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