5-氘代利巴韦林衍生物的合成  

Synthesis of 5-Deuterated Ribavirin Derivative

作　　者：杨玉萍[1] 徐绍红[1] 马国扬 焦黎明 孙莉萍[2] 夏然[1] YANG Yu-Ping;XU Shao-Hong;MA Guo-Yang;JIAO li-Ming;SUN Li-Ping;XIA Ran(School of Pharmacy,Xinxiang University,Xinxiang 453003,China;School of Life Sciences&Basic Medicine,Xinxiang University,Xinxiang 453003,China)

机构地区：[1]新乡学院药学院,新乡453003 [2]新乡学院生命科学与基础医学学院,新乡453003

出　　处：《应用化学》2021年第8期911-916,共6页Chinese Journal of Applied Chemistry

基　　金：国家自然科学基金(No.21602189);河南省高等学校青年骨干教师培养计划(No.2020GGJS248);大学生创新创业训练国家级项目(No.202011071011)资助。

摘　　要：报道了5位被氘原子取代的抗病毒药物利巴韦林的合成新方法。在曙红Y(Eosin Y)催化和蓝光照射下,5-巯基-3-甲基-1,2,4-三氮唑的硫原子转化为氘原子,接着甲基被KMnO4氧化为羧基,然后在H2SO4/CH3OH体系中羧基发生甲酯化反应,得到5-氘代-1,2,4-三氮唑甲酯。最后5-氘代-1,2,4-三氮唑甲酯和1,2,3,5-四-O-乙酰基-β-D-呋喃核糖缩合、氨解,以5步和51.7%的总收率得到5-氘代利巴韦林。该方法避免使用重金属催化剂,原料廉价易得,且反应规模可以扩大到20 g,为利巴韦林衍生物的研究提供了新的途径。5-Deuterated ribavirin,as a derivative of an antiviral drug ribavirin,of which the hydrogen atom on C5 was substituted by a deuterium atom,was synthesized in 51.7%total yield by 5-step reactions.The key intermediate 5-deuterated-1,2,4-triazole methyl ester was synthesized from 5-mercapto-3-methyl-1,2,4-triazole via three steps:firstly,5-mercapto was transformed into the deuterium atom under the catalysis of Eosin Y and blue light irradiation;secondly,the methyl group was oxidized to the carboxyl group with KMnO4;thirdly,the carboxyl group was transformed into methyl ester in H2SO4/CH3OH system.Finally,the 5-deuterated ribavirin was synthesized via the condensation of 5-deuterated-1,2,4-triazole methyl ester with 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose and then ammonolysis.This method avoides the use of heavy metal catalysts from cheap raw materials,and the reaction scale could be expanded to 20 g,which provides a new way for the research of ribavirin derivatives.

关 键 词：利巴韦林 氘代药物 脱硫反应 光催化 

分 类 号：O622.1[理学—有机化学]