(S)-2-Chloro-1-(3,4-difluorophenyl)-ethanol [(S)-CFPL] is a key chiral intermediate in the manufacture of Ticagrelor. In this study, deep eutectic solvent (DES) was used as the co-solvent, and several reaction parameters were investigated and characterized. It was observed that supplementary of DES could promote the asymmetric reduction of 2‑chloro-1-(3,4-difluorophenyl) ethanone (CFPO) to (S)-CFPL through the biological reduction by recombinant E. coli containing a NADH-dependent reductase CmCR. The high pKa value of carboxylic acid in DES and low viscosity of DES were beneficial to increase cell membrane permeability and enhancement of biocatalytic efficiency. By supplementary of DES ChCl:LA (7.5 vol%) into the bioreaction system, the efficient bioreduction reaction of 100 mM CFPO was achieved via the biocatalysis with whole-cell at 30 °C and pH 7.0, affording (S)-CFPL in 95.9 % yield and optical purity > 99 %. The process was environmentally friendly with high biocatalytic productivity and had potential practicability in the mass production of (S)-CFPL.

( S )-2-氯-1-(3,4-二氟苯基)-乙醇[( S )-CFPL]是替格瑞洛生产中的关键手性中间体。在本研究中，使用低共熔溶剂（DES）作为共溶剂，并对几个反应参数进行了研究和表征。研究发现补充DES可以促进重组大肠杆菌通过生物还原将2-氯-1-(3,4-二氟苯基)乙酮(CFPO)不对称还原为( S )-CFPL含有 NADH 依赖性还原酶 CmCR。DES中羧酸的高pKa值和DES的低粘度有利于增加细胞膜的通透性和提高生物催化效率。通过向生物反应系统中添加DES ChCl:LA (7.5 vol%)，在30 °C、pH 7.0下通过全细胞生物催化实现100 mM CFPO的高效生物还原反应，得到95.9的(S) -CFPL %收率和光学纯度> 99 %。该工艺环境友好，生物催化产率高，在( S )-CFPL的大规模生产中具有潜在的实用性。