Abstract As the key chiral intermediate of luliconazole, (S)-2-chloro-1-(2, 4-dichlorophenyl) ethanol ((S)-CPEO) was prepared from 2-chloro-1-(2, 4-dichlorophenyl) ethanone (CPE) using a tetrad mutant alcohol dehydrogenase (A94T/F147L/L199H/A202L) from Lactobacillus kefir (LK-TADH) coupled with glucose dehydrogenase (GDH). Enzyme-substrate docking simulation was used to reveal the molecular basis of the increases in catalytic ability and enantiomeric excess (ee) values of LK-TADH. Furthermore, using 60 g/L of CPE for gram-scale preparation of (S)-CPEO, the conversion rate reached approximately 100% after 6 h at 35 °C, and the ee value of the final product was 99.5%. Our research provides a foundation for preparing of (S)-CPEO using LK-TADH.

中文翻译：

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使用来自开菲尔乳杆菌的四联体突变醇脱氢酶高效合成 (S)-2-chloro-1-(2, 4-dichlorophenyl) 乙醇

摘要 以2-氯-1-(2, 4-二氯苯基)为原料制备(S)-2-氯-1-(2, 4-二氯苯基)乙醇((S)-CPEO)为卢立康唑的关键手性中间体。乙酮 (CPE) 使用来自开菲尔乳杆菌 (LK-TADH) 的四联体突变醇脱氢酶 (A94T/F147L/L199H/A202L) 与葡萄糖脱氢酶 (GDH) 偶联。酶底物对接模拟用于揭示 LK-TADH 催化能力和对映体过量 (ee) 值增加的分子基础。此外，使用 60 g/L 的 CPE 进行克级规模制备 (S)-CPEO，在 35°C 下 6 小时后转化率达到约 100%，最终产品的 ee 值为 99.5%。我们的研究为使用 LK-TADH 制备 (S)-CPEO 奠定了基础。