通过不对称氢转移/动态动力学拆分合成碳环N^3-嘌呤核苷  

Asymmetric Transfer Hydrogenation via Dynamic Kinetic Resolution for the Construction of Carbocyclic N^3-Purine Nucleosides

作　　者：张齐英 张一铭 郝二军 白娟 渠桂荣 郭海明 Zhang Qiying;Zhang Yiming;Hao Erjun;Bai Juan;Qu Guirong;Guo Haiming(Henan Key Laboratory of Organic Functional Molecules and Drug Innovation,Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals,Key Laboratory of Green Chemical Media and Reactions,Ministry of Education,School of Chemistry and Chemical Engineering,Henan Normal University,Xinxiang,Henan 453007)

机构地区：[1]河南师范大学化学化工学院,绿色化学介质与反应教育部重点实验室,精细化学品绿色制造河南省协同创新中心,河南省有机功能分子与药物创新重点实验室,河南新乡453007

出　　处：《有机化学》2020年第2期376-383,共8页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(Nos.21602045,U1604283);高等学校学科创新引智计划(111计划,No.D17007)资助项目.

摘　　要：N^3-嘌呤核苷由于可能同时被嘌呤和嘧啶代谢酶识别,因而有望作为双靶点药物应用于抗病毒治疗.报道了一种以α-(N^3-嘌呤)取代的环烷酮为原料,通过不对称氢转移反应实现动态动力学拆分,高收率高立体选择性地合成系列碳环N^3-嘌呤核苷化合物.该催化体系也适用于α-嘧啶取代的环烷酮底物,且产物通过进一步衍生,合成了2’-F-,Ac S-,N^3-修饰的碳环嘧啶核苷.N^3-Purine nucleoside can be employed as a potent dual inhibitor to inhibit viruses more effectively because it could be possibly recognized by both purine-and pyrimidine-metabolizing enzymes. Herein, an asymmetric transfer hydrogenation via dynamic kinetic resolution of rac-α-(purin-3-yl)cyclopentones has been developed to produce a wide range of carbocyclic N^3-purine nucleosides in high yields and excellent stereoselectivities. Moreover, the catalytic system was suitable for rac-α-pyrimidinyl cyclopentones. With additional transformations, several 2’-F-, AcS-, N^3-modified carbocyclic nucleosides could be obtained with good to excellent yields and excellent enantioselectivities.

关 键 词：碳环核苷 双靶点抑制剂 动态动力学拆分 不对称氢转移反应 

分 类 号：TQ460.1[化学工程—制药化工]