嘌呤核苷磷酸化酶抑制剂呋咯地辛的合成  

Synthesis of purine nucleoside phosphorylase inhibitor Forodesine

作　　者：欧景丹 张敏杰[1] 李鹏 薛斐 秦勇[1] OU Jingdan;ZHANG Minjie;LI Peng;XUE Fei;QIN Yong(West China School of Phannacy,Sichuan University,Chengdu,Sichuan,610041 P.R.China)

机构地区：[1]四川大学华西药学院,四川成都610041

出　　处：《华西药学杂志》2021年第5期495-500,共6页West China Journal of Pharmaceutical Sciences

基　　金：国家自然科学基金资助项目(批准号:21702140)。

摘　　要：目的设计嘌呤核苷磷酸化酶抑制剂呋咯地辛(Forodesine)的新合成路线。方法以手性环状硝酮和5H-吡咯并[3,2-d]嘧啶衍生物为原料,经可见光催化的杂环C-H官能化合成关键中间体C-氮杂核苷类似物,再经还原、引入Boc保护基、脱保护等步骤得到目标化合物。结果与结论该路线以4步、22%总收率成功制备了呋咯地辛,合成中的关键步骤为利用可见光催化实现硝酮和杂环的C-C键偶联,为合成C-氮杂核苷类似物发展了一种新方法。OBJECTIVE To design a novel synthetic route for purine nucleoside phosphorylase inhibitor Forodesine.METHODS By employing chiral cyclic nitrone and 5H-pyrrolo[3,2-d]pyrimidine derivative as substrates, the key intermediate C-azanucleoside analogue was obtained via visible-light photocatalytic C-H functionalization of the heterocyclic compound.The former was then transformed into Forodesine through reduction, Boc protection and deprotection.RESULTS and CONCLUSION The synthesis of Forodesine was achieved in 4 steps with a total yield of 22%.The key step features a visible-light photocatalytic C-C bond formation of the nitrone and the heterocylic compound, which provides a novel access to synthesize C-azanucleoside analogues.

关 键 词：嘌呤核苷磷酸化酶抑制 呋咯地辛 C-氮杂核苷类似物 可见光催化 手性硝酮 药物合成 碳-碳键构建 C-H官能化 

分 类 号：R914[医药卫生—药物化学]