4,6-二苄基-3-氰基-2(1H)-吡啶酮的合成及抗HIV-1活性

doi:10.5246/jcps.2011.05.056

4,6-二苄基-3-氰基-2(1H)-吡啶酮的合成及抗HIV-1活性

李阿敏, 刘香宜, 王孝伟^*, 刘俊义^*

北京大学医学部药学院化学生物学系, 北京 100191

收稿日期:2011-05-19 修回日期:2011-07-20 出版日期:2011-09-20 发布日期:2011-09-20
通讯作者: 王孝伟*, 刘俊义*

Design, synthesis and anti-HIV-1 activity of 4,6-dibenzyl-2-oxo-1,2-dihydropyridine-3-carbonitrile

A-Min Li, Xiang-Yi Liu, Xiao-Wei Wang^*, Jun-Yi Liu^*

Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2011-05-19 Revised:2011-07-20 Online:2011-09-20 Published:2011-09-20
Contact: Xiao-Wei Wang*, Jun-Yi Liu*

摘要/Abstract

摘要： 本文报道了4,6-二苄基-3-氰基-2(1H)-吡啶酮的合成方法。合成了重要中间体3-氧代-4-苯基丁酸乙酯, 为合成不同的6位取代的吡啶酮类化合物提供方法。对合环产物的脱羧条件进行了优化, 经过甲氧基保护, 以n-BuLi作为强碱, 与溴苄反应得到目标化合物11。其结构经¹H NMR, ¹³C NMR和高分辨质谱分析确证, 并对该化合物的抗HIV-1活性进行了测定。

关键词: HIV-1, NNRTIs, 吡啶酮, 脱羧反应

Abstract:

An effective synthesis method for preparing 4,6-disubstituted pyridinones was reported. Ethyl 3-oxo-4-phenylbutyrate was an important intermediate, by which 6-substituted pyridinones could be prepared. The decarboxylation condition was optimized for compound 4. After protected with a methoxy group, the compound was reacted with BnBr to form the target compound 11. The structures were characterized by ¹H NMR, ¹³C NMR and HRMS, and its enzyme inhibition activity was also determined.

Key words: HIV-1, NNRTIs, Pyridinone analogues, Decarboxylation

中图分类号:

R916

Supporting:

Foundation items: National Natural Science Foundation of China (Grant No. 20972011 and 21042009).
^*Corresponding author. Tel.: 86-10-82805203

李阿敏, 刘香宜, 王孝伟^*, 刘俊义^*. 4,6-二苄基-3-氰基-2(1H)-吡啶酮的合成及抗HIV-1活性[J]. , DOI: 10.5246/jcps.2011.05.056.

A-Min Li, Xiang-Yi Liu, Xiao-Wei Wang^*, Jun-Yi Liu^*. Design, synthesis and anti-HIV-1 activity of 4,6-dibenzyl-2-oxo-1,2-dihydropyridine-3-carbonitrile [J]. , DOI: 10.5246/jcps.2011.05.056.

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