Efficient Synthesis of (R)-2-Chloro-1-(3-chlorophenyl)ethanol by Permeabilized Whole Cells of Candida ontarioensis

(R)-2-Chloro-1-(3-chlorophenyl)ethanol is a key pharmaceutical intermediate in the synthesis of 3-adrenoceptor receptor (3-AR) agonists. The asymmetric reduction of 2-chloro-1-(3-chlorophenyl)ethanone to (R)-2-chloro-1-(3-chlorophenyl)ethanol catalyzed by resting cells of Candida ontarioensis was studied. At a substrate concentration of 10 g/L, the microbial cells showed excellent catalytic activity under the optimum reaction conditions, giving the product in 99.9% ee and 99.0% yield. After cetyltrimethylammonium bromide-pretreatment, the activity of permeabilized Candida ontarioensis cells was increased by more than 2-fold and the product could be produced over the significantly shortened reaction period of 24 h in 99.9% ee and 97.5% yield at a substrate concentration of 30 g/L. This work provides a practical approach for the efficient preparation of the important chiral intermediate (R)-2-chloro-1-(3-chlorophenyl) ethanol.

摘要考察了利用安大略假丝酵母 (Candida ontarioensis) 静息细胞不对称催化 2-氯-1-(3-氯苯基) 乙酮合成 (R)-2-氯-1-(3-氯苯基) 乙醇的转化反应条件. 结果表明, 当底物浓度为 10 g/L 时, 在最适转化条件下反应 72 h, 产物的 ee 值和产率分别达到 99.9% 和 99.0%. 采用 4 g/L 十六烷基三甲基溴化铵对 Candida ontarioensis 细胞于 4 °C 通透性处理 20 min 后, 全细胞的酶活提高 2 倍以上. 当底物浓度提高为 30 g/L, 转化 24 h 后, 产物的 ee 和产率分别达到 99.9% 和 97.5%. 该研究为高效制备 (R)-2-氯-1-(3-氯苯基) 乙醇提供了可行途径, 并为生物催化合成芳基手性醇类手性中间体提供了理论指导.

The catalytic efficiency of cetyltrimetylammonium bromide (CTAB)-permeabilized Candida ontarioensis whole cells has been significantly enhanced. The reaction time for the asymmetric synthesis of (R)-2-chloro-1-(3-chlorophenyl)ethanol was reduced from 72 to 24 h.Figure optionsDownload as PowerPoint slide