催化学报

催化学报 ›› 2012, Vol. 33 ›› Issue (4): 681-687.DOI: 10.1016/S1872-2067(11)60363-X

• 研究论文 • 上一篇    下一篇

采用通透性处理的安大略假丝酵母全细胞高效合成 (R)-2-氯-1-(3-氯苯基)乙醇

倪晔*, 张蓓花, 孙志浩   

  1. 江南大学生物工程学院, 工业生物技术教育部重点实验室, 江苏无锡 214122
  • 收稿日期:2011-11-02 修回日期:2012-01-06 出版日期:2012-04-13 发布日期:2015-09-09

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

NI Ye*, ZHANG Beihua, SUN Zhihao   

  1. The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, Jiangsu, China
  • Received:2011-11-02 Revised:2012-01-06 Online:2012-04-13 Published:2015-09-09

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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.

关键词: (R)-2-氯-1-(3-氯苯基)乙醇, 不对称还原, 十六烷基三甲基溴化铵, 通透性, Candida ontarioensis

Abstract: (R)-2-Chloro-1-(3-chlorophenyl)ethanol is a key pharmaceutical intermediate in the synthesis of β3-adrenoceptor receptor (β3-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.

Key words: (R)-2-chloro-1-(3-chlorophenyl)ethanol, asymmetric reduction, cetyltrimethylammonium bromide, permeability, Candida ontarioensis