雷公藤内酯醇乏氧激活前药的合成与结构表征
Synthesis and Characterization of Hypoxia Actived Prodrug of Triptolide
张冬梅 1阙慧卿 1李唯1
作者信息
- 1. 福建省医学科学研究院 福建省医学测试重点实验室,福建 福州 350001
- 折叠
摘要
(目的)制备雷公藤内酯醇乏氧激活前药,并对其结构进行表征;合成了Gem1 和Dox1.总计合成了三个乏氧激活前药,用于后续抗肿瘤实验研究.(方法)2-硝基咪唑通过亲核取代反应,水解反应得到3-(2-硝基-1H-咪唑-1-基)丙酸.3-(2-硝基-1H-咪唑-1-基)丙酸再与雷公藤内酯醇、多柔比星和吉西他滨通过缩合反应得到目标化合物——Gem1 和Dox1,采用核磁共振氢谱和高分辨质谱确认其结构.(结果)成功得到目标化合物——Gem1 和Dox1.(结论)研究采用核磁共振氢谱和高分辨质谱确认了目标化合物——Gem1 和Dox1 的结构,成功合成的三个乏氧激活前药,为后续抗肿瘤研究奠定基础.
Abstract
(OBJECTIVE)The hypoxia actived prodrug of triptolide was synthesized,and its structure was confirmed.Additionally,two con-trol compounds Gem1 and Dox1 were prepared.In total,three Hypoxia actived prodrugs were obtained in order to further antitumor study.(METHOD)We used 2-nitroimidazole as the starting material.Subsequently,3-(2-nitro-1H-imidazole-1-yl)propionic acid has been yielded through nucleophilic substitution and hydrolysis.The target compounds,Gem1 and Dox1 were obtained by condensation reaction of 3-(2-nitro-1H-imidazol-1-yl)propionic acid with triptolide,doxorubicin,and gemcitabine,respectively.And their structures were confirmed using 1H-NMR and high-resolution mass spectrometry.(RESULTS)we successfully obtained the target compound and Dox1 and Gem1.(CONCLUSION)the structures of target compound and Dox1 and Gem1 were confirmed by 1H-NMR and high-resolution mass spectrometry.Three hypoxia activated prodrugs were successfully obtained in order to do further antitumor studies.
关键词
雷公藤内酯醇/乏氧激活前药/抗肿瘤Key words
triptolide/hypoxia activated prodrug/antitumor引用本文复制引用
基金项目
福建省卫生健康委青年科研课题(2020QNA022)
出版年
2024
国家科技期刊平台
NSTL
维普
万方数据