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

作　　者：张冬梅 阙慧卿 李唯 Zhang Dongmei;Que Huiqing;Li Wei(Fujian Key Laboratory of Medical Analysis,Fujian Academy of Medical Sciences,Fuzhou 350001,China)

机构地区：[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

出　　处：《云南化工》2024年第1期34-37,共4页Yunnan Chemical Technology

基　　金：福建省卫健委青年科研课题(2020QNA022)。

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。(OBJECTIVE)The hypoxia actived prodrug of triptolide was synthesized,and its structure was confirmed.Additionally,two control 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 

分 类 号：R961[医药卫生—药理学]