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

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.