对黄藤素进行结构修饰,采用160~180℃高温热解使黄藤素选择性在9-位脱甲基,再分别与一系列酰氯发生酯化反应,最终获得12种黄藤素衍生物,经1H-NMR、13C-NMR分析确定了各衍生物的化学结构,分别为:9-O-苯甲酰基-黄藤素(9-O-Benzoyl-fibrauretin)、9-O-(2-甲基苯甲酰基)-黄藤素(9-O-(2-Methylbenzoyl)-fibrauretin)、9-O-(4-甲基苯甲酰基)-黄藤素(9-O-(4-Methylbenzoyl)-fibrauretin)、9-O-(3,5-二甲基苯甲酰基)-黄藤素(9-O-(3,5-Dimethylbenzoyl)-fibrauretin)、9-O-(4-(氯甲基)苯甲酰基)-黄藤素(9-O-(4-(Chloromethyl) benzoyl)-fibrauretin)等共12种化合物,均为新化合物.采用以碘化硫代乙酰胆碱为底物、来源于苍蝇头部的乙酰胆碱酯酶(AChE)为酶源的体外活性测定方法,测定了黄藤素及其衍生物的AChE抑制活性.结果表明,大部分黄藤素酰氯衍生物体外AChE抑制活性均强于黄藤素,其中化合物9-O-(4-甲基苯甲酰基)-黄藤素、9-O-(3,5-二甲基苯甲酰基)-黄藤素、9-O-(4-(氯甲基)苯甲酰基)-黄藤素对AChE的抑制作用显著,活性强度强于阳性药盐酸多奈哌齐,具有开发成抗阿尔茨海默症药物的潜力.%The structure of fibrauretin made by our lab was modified. Fibrauretin was demethylated at 9-site under high temperature pyrolysis at 160℃-180℃ and was reacted with a series of acid chlorides. Twele derivatives of fibrauretin were obtained. The structure of each derivative was determined by1H-NMR and13C-NMR. The derivatives were 9-O-benzoyl-fibrauretin, 9-O-( 2-methylbenzoyl)-fibrauretin, 9-O-( 4-methylbenzoyl)-fibrauretin, 9-O-(3, 5-dimethylbenzoyl)-fibrauretin, 9-O-(4-(chloromethyl) benzoyl)-fibrauretin and other derivatives. The 12 derivatives are all new chemical compounds. Taking ATCI as substrate,the inhibitory activity on acetylcholinesterase (AChE) from the head of flies of the fibrauretin and its derivatives were screened. The results showed that most of the derivatives had improved their inhibitory activity on AChE through esterification reaction. Compounds 9-O-(4-methylbenzoyl)-fibrauretin, 9-O-(3,5-dimethylbenzoyl)-fibrauretinand 9-O-(4-(chloromethyl)benzoyl)-fibrauretin had significant inhibitory effect on AChE,and the inhibitory activity was stronger than the that of donepezil.
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