摘要/Abstract
建立了一种新颖的、“一锅煮”的化学-酶法合成手性α-卤代芳基醇.从价廉易得的芳基酮出发，经对甲苯磺酸催化芳基酮卤代合成α-卤代芳基酮，无需中间产物分离，直接在反应体系中加入具有羰基还原酶活性的红酵母（Rhodotorula sp.） AS2.2241的静息细胞即可催化α-卤代芳基酮不对称还原为手性的α-卤代芳基醇.在对每一步反应都详细优化的基础上，对两步反应的偶联条件做了细致研究，发现控制生物催化反应体系的有机溶剂含量和pH值是解决生物相容性问题的关键.在最优的反应条件和偶联条件下合成了四种手性α-卤代芳基醇，产率和ee值都较高，分别 > 95%和 > 99%.
关键词: 一锅法, 化学-酶法合成, 手性α-卤代芳基醇, 生物催化, 绿色化学
A novel one-pot chemo-enzymatic method was developed for the preparation of chiral α-halogenated aryl alcohols from cheap aryl ketones. Firstly, the α-halogenated aryl ketones were obtained via halogenation of aryl ketones catalyzed by p-toluenesulfonic acid. Then, α-halogenated aryl ketones was asymmetric reduced to chiral α-halogenated aryl alcohols by adding cell suspension of Rhodotorula sp. AS2.2241 with carbonyl reductase activity into the reaction system without isolating intermediate products. The best reaction condition was optimized for each step and the coupling condition of chemical and biological reaction was studied in detail. It was found that the concentration of organic solvent and the pH value are key factors that affect the enzyme activity of biocatalytic reaction. Under optimized reaction and coupling conditions, four kinds of chiral α-halogenated aryl alcohols were obtained with high yield and high optical purity (yield > 95%, ee > 99%).
Key words: one-pot reaction, chemo-enzymatic synthesis, chiral α-halogenated aryl alcohol, biocatalysis, green chemistry
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