title: Efficient enantioselective synthesis of (R)-[3,5-bis(trifluoromethyl)phenyl] ethanol by Leifsonia xyli CCTCC M 2010241 using isopropanol as co-substrate.
abstract: (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 200 mM of 3,5-bis(trifluoromethyl) acetophenone, 20% (v/v) of isopropanol, and 300 g/l of wet cells. The bioreduction was executed at 30°C 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.
authors: College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China.
authors: Qi
authors: Q
authors: Ouyang
authors: Pu
authors: P
authors: Wang
authors: Jin
authors: J
authors: Huang
authors: Jinbo
authors: J
authors: Cai
authors: Junyao
authors: J
authors: He
mesh_terms: D019840:2-Propanol / Q000378:metabolism*; D000098:Acetophenones / Q000378:metabolism; D000192:Actinomycetales / Q000378:metabolism*; D001709:Biotechnology / Q000379:methods*; D001711:Biotransformation; D006845:Hydrocarbons, Fluorinated / Q000378:metabolism*; D013696:Temperature; D013997:Time Factors
chemical_list: D000098:Acetophenones; D006845:Hydrocarbons, Fluorinated; D019840:2-Propanol