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(英文)

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

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10g/L时,在最适转化条件下反应72h,产物的ee值和产率分别达到99.9%和99.0%.采用4g/L十六烷基三甲基溴化铵对Candida ontarioensis细胞于4℃通透性处理20min后,全细胞的酶活提高2倍以上.当底物浓度提高为30g/L,转化24h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。

（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.