Synthesis of 5-Deuterated Ribavirin Derivative

doi:10.19894/j.issn.1000-0518.200379

Chinese Journal of Applied Chemistry ›› 2021, Vol. 38 ›› Issue (8): 911-916.DOI: 10.19894/j.issn.1000-0518.200379

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Synthesis of 5-Deuterated Ribavirin Derivative

YANG Yu-Ping¹, XU Shao-Hong¹, MA Guo-Yang¹, JIAO Li-Ming¹, SUN Li-Ping^2*, XIA Ran^1*

¹School of Pharmacy, Xinxiang University, Xinxiang 453003, China
²School of Life Sciences & Basic Medicine, Xinxiang University, Xinxiang 453003, China

Received:2020-12-16 Revised:2021-03-16 Published:2021-08-01 Online:2021-10-01
Supported by:
National Natural Science Foundation of China (No.21602189), the Project for Young Core Teacher in Universities of Henan Province (No.2020GGJS248) and the National Undergraduate Innovation and Entrepreneurship Training Program (No.202011071011)

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Abstract

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

CLC Number:

O622.1

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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Synthesis of 5-Deuterated Ribavirin Derivative

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