Regioselective and enantioselective propargylic hydroxylations catalyzed by P450tol monooxygenases  

作　　者：Xu Deng Cheng-Cheng Song Wen-Jing Gu Yu-Jie Wang Lu Feng Xiao-Jian Zhou Ming-Qiang Zhou Wei-Cheng Yuan Yong-Zheng Chen 

机构地区：[1]Key Laboratory of Biocatalysis&Chiral Drug Synthesis of Guizhou Province,Key Laboratory of Basic Pharmacology of Ministry of Education,School of Pharmacy,Zunyi Medical University,Zunyi,China [2]National Engineering Research Center of Chiral Drugs,Chengdu Institute of Organic Chemistry,Chinese Academy of Sciences,Chengdu 610041,China

出　　处：《Bioresources and Bioprocessing》2024年第1期855-863,共9页生物资源与生物加工(英文)

基　　金：financial support from the National Natural Science Foundation of China(No.32271537 and 22061049);the Science and Technology Department of Guizhou province(QKHJCZK2021-036 and QKHRCPTGCC-2023-003);the Science and Technology Department of Zunyi(ZSKRPT-2020-5,ZSKH-2018-3,ZSKRPT-2021-5);Zunyi Medical University(QKH-2018-5772-014).

摘　　要：Regioselective and enantioselective hydroxylation of propargylic C-H bonds are useful reactions but often lack appropriate catalysts.Here a green and efficient asymmetric hydroxylation of primary and secondary C-H bonds at propargylic positions has been established.A series of optically active propargylic alcohols were prepared with high regio-and enantioselectivity(up to 99%ee)under mild reaction conditions by using P450tol,while the C≡C bonds in the molecule remained unreacted.This protocol provides a green and practical method for constructing enantiomerically chiral propargylic alcohols.In addition,we also demonstrated that the biohydroxylation strategy was able to scaled up to 2.25 mmol scale with the production of chiral propargyl alcohol 2a at a yield of 196 mg with 96%ee,which’s an important synthetic intermediate of antifungal drug Ravuconazole.

关 键 词：BIOCATALYSIS HYDROXYLATION P450 monooxygenase Propargylic alcohols ENANTIOSELECTIVITY 

分 类 号：O62[理学—有机化学]