Asymmetric synthesis of syn-aryl-(2S,3R)-2-chloro-3-hydroxy esters via an engineered ketoreductase-catalyzed dynamic reductive kinetic resolution  

作　　者：Xiaoping Yue Yitong Li Di Sang Yuan Tao Zedu Huang Fener Chen 

机构地区：[1]Sichuan Research Center for Drug Precision Industrial Technology,West China School of Pharmacy,Sichuan University,Chengdu 610041,China [2]Engineering Center of Catalysis and Synthesis for Chiral Molecules,Department of Chemistry,Fudan University,Shanghai 200433,China [3]Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs,Shanghai 200433,China

出　　处：《Chinese Chemical Letters》2023年第9期156-159,共4页中国化学快报（英文版）

基　　金：The National Key Research and Development Program of China(Nos.2021YFA0911400 and 2021YFF0600704);the National Natural Science Foundation of China(Nos.22071033 and 21801047)are acknowledged for the financial supports。

摘　　要：We report here a generic,green synthesis of 17 valuable syn-aryl-(2S,3R)-2–chloro-3–hydroxy esters(syn-(2S,3R)-1)in 73%-99%isolated yields along with 6.1:1–83:1 dr and 31%~>99%ee,through dynamic reductive kinetic resolution of racemic arylα–chloroβ-keto esters(2)catalyzed by an engineered ketoreductase which was obtained via ep PCR-based directed evolution.The hectogram scale synthesis of syn-(2S,3R)-1b at a substrate concentration of 120 g/L showcased the application potential of the biocatalytic method developed presently.

关 键 词：(2S 3R)-2-Chloro-3-hydroxy esters Dynamic reductive kinetic resolution KETOREDUCTASE Directed evolution Asymmetric synthesis 

分 类 号：O625.523[理学—有机化学]