新型12-N-取代苦参酸衍生物的合成及其抗结核活性  

Synthesis and Antitubercular Activities of Novel 12-N-substituted Matrinic Acid Derivatives

作　　者：付海根 唐胜[1] 李迎红[1] 宋丹青[1] 汪燕翔[1] 

机构地区：[1]中国医学科学院北京协和医学院医药生物技术研究所,北京100050

出　　处：《合成化学》2014年第6期739-743,共5页Chinese Journal of Synthetic Chemistry

基　　金："十二五重大新药创制"科技重大专项资助项目(2012ZX09301002-001-017)

摘　　要：以苦参碱为起始原料,经水解开环,羧基保护制得中间体苦参酸甲酯(3);3与烷基溴或取代酰氯分别经烷基化反应、酰基化反应和磺酰化反应在12-N原子上引入不同结构类型的基团制得新化合物——12-N-取代基苦参丁甲酯(5a^5d);5再经酯水解或Li ALH4还原反应合成了一系列新型的12-N-取代基苦参酸或12-N-取代基苦参酸丁醇,其结构经1H NMR,13C NMR和HR-ESI-MS表征。初步的体外生物活性测试结果表明,12-N-正十二烷基苦参丁甲酯具有较佳的抗结核活性,对敏感结核菌株H37Rv的MIC为8.0μg·m L-1。A intermediate,methyl matrinate（ 3）,was prepared by hydrolytic loop-open and carboxyl protection from matrine. Five novel methyl 12-N-substituted matrinate（ 5a - 5d） were synthesized by alkylation（ or acylation or sulfonyl） of 3 with alkylbramides or substituted-acylchloride. A series of novel structural nucleus——12-N-substituted matrinic acid derivatives were synthesized by hydrolysis or reduction of esters of 5. The structures were characterized by^1 H NMR,^13 C NMR and HR-ESIMS. Primary against Mycobacterium tuberculosis strain H37 Rv activity tests indicated that methyl-12-N-dodecyl-matrinate exhibited a potent anti-mycobacterial activity with MIC value of 8. 0 μg·mL^- 1.

关 键 词：苦参碱 12-N-取代基苦参酸 合成 抗结核活性 构效关系 

分 类 号：O621.3[理学—有机化学] R914.5[理学—化学]