摘要
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p H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%.
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, a-halogenated aryl ketones was asymmetric reduced to chiral α-halogenated aryl alcohols by adding cell suspension ofRhodotorula 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%）.
作者
杨靖文
陈建波
王诗婕
吴小梅
马宝娣
徐毅
Yang Jingwen;Chen Jianbo;Wang Shijie;Wu Xiaomei;Ma Baodi;Xu Yi(School of Chemical and Environmental Engineering,Shanghai Institute of Technology,Shanghai 201418;College of Life and Environment Science,Shanghai Normal University,Shanghai 200234)
出处
《有机化学》
SCIE
CAS
CSCD
北大核心
2018年第7期1811-1816,共6页
Chinese Journal of Organic Chemistry
基金
上海市科委重点基金(No.13430503400)
教育部留学回国人员基金(No.ZX2012-05)资助项目~~
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
one-pot reaction
chemo-enzymatic synthesis
chiral α-halogenated aryl alcohol
biocatalysis
green chemistry
