5-氘代利巴韦林衍生物的合成

doi:10.19894/j.issn.1000-0518.200379

摘要/Abstract

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。

关键词: 利巴韦林, 氘代药物, 脱硫反应, 光催化

Abstract: 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.

Key words: Ribavirin, Deuterated drugs, Desulfurization, Photocatalysis

中图分类号:

O622.1

杨玉萍, 徐绍红, 马国扬, 焦黎明, 孙莉萍, 夏然. 5-氘代利巴韦林衍生物的合成[J]. 应用化学, 2021, 38(8): 911-916.

YANG Yu-Ping, XU Shao-Hong, MA Guo-Yang, JIAO Li-Ming, SUN Li-Ping, XIA Ran. Synthesis of 5-Deuterated Ribavirin Derivative[J]. Chinese Journal of Applied Chemistry, 2021, 38(8): 911-916.

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