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.
出处
《合成化学》
CAS
CSCD
北大核心
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)
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
matrine
12-N-substituted matrinic acid
synthesis
antitubercular
structure-activity relationship
