(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.

中文翻译：

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利用异丙醇作为共底物，通过Leifsonia xyli CCTCC M 2010241有效地对映体（R）-[3,5-双（三氟甲基）苯基]乙醇的对映选择性合成。

（R）-[3，5-双（三氟甲基）苯基]乙醇是合成aprepitant的关键手性中间体。本文通过Leifsonia xyli CCTCC M 2010241细胞催化不对称还原3,5-双（三氟甲基）苯乙酮，开发了一种有效的合成（R）-[3,5-双（三氟甲基）苯基]乙醇的方法。使用异丙醇作为辅因子循环的辅助底物。首先，通过在反应体系中添加不同的共底物，评估了生物催化剂的底物和产物的溶解度以及细胞膜的渗透性，其中异丙醇在3,5-双（三氟甲基）的生物还原过程中表现出偶联NADH再生的最佳氢供体。 ）苯乙酮。随后，进行了生物还原参数的优化，以提高该过程的有效性。确定的有效反应系统包含200 mM的3,5-双（三氟甲基）苯乙酮，20％（v / v）的异丙醇和300 g / l的湿细胞。在30℃和200rpm下进行生物还原30小时，获得了91.8％的产物收率和99.9％的对映体过量（ee）。建立的生物还原反应系统可以耐受更高浓度的3,5-双（三氟甲基）苯乙酮底物浓度，并为所需的（R）-手性醇提供令人满意的收率和出色的产物ee，从而为（ R）-[3，5-双（三氟甲基）苯基]乙醇。获得了8％的产物收率和99.9％的对映体过量（ee）。建立的生物还原反应系统可以耐受更高浓度的3,5-双（三氟甲基）苯乙酮底物浓度，并为所需的（R）-手性醇提供令人满意的收率和出色的产物ee，从而为（ R）-[3，5-双（三氟甲基）苯基]乙醇。获得了8％的产物收率和99.9％的对映体过量（ee）。建立的生物还原反应系统可以耐受更高浓度的3,5-双（三氟甲基）苯乙酮底物浓度，并为所需的（R）-手性醇提供令人满意的收率和出色的产物ee，从而为（ R）-[3，5-双（三氟甲基）苯基]乙醇。