4-甲基伞形内酯衍生物的合成与生物活性研究

4-甲基伞形内酯(4-甲基-7-羟基香豆素, 1)是一种具有重要生物活性的香豆素类天然产物. 本文以间苯二酚和乙酰乙酸乙酯为原料, 经Pechmann反应合成4-甲基伞形内酯(1). 然后以4-甲基伞形内酯(1)为底物, 分别经Mannich反应、乙酰化、Fries重排、O-甲基化、Baeyer-Villiger氧化、O-异戊烯基化和Claisen重排等反应步骤, 合成了一系列4-甲基伞形内酯衍生物2~10.并对所合成的化合物进行了人宫颈癌Hela细胞的抑制活性测试, 结果发现新化合物4-甲基5-异戊烯基-8-羟基-7-甲氧基香豆素(10)对Hela细胞的抑制活性(IC50 = 28.58 μmol/L), 高于阳性对照药物顺铂(IC50 = 41.25 μmol/L), 具有进一步研究开发的价值.
4-Methylumbelliferone (4-methyl-7-hydroxycoumarin, 1) is a coumarins natural product with important biological activity. Firstly, 4-methylumbelliferone (1) was synthesized from resorcinol and ethyl acetoacetate by Pechmann reaction. Nine coumarin derivatives (2~10) were then synthesized through Mannich reaction, acetylation, Fries rearrangement, O-methylation, Baeyer-Villiger oxidation, O-prenylation and Claisen rearrangement from 4-methylumbelliferone (1). Their inhibitory activities on human cervical carcinoma Hela cells were evaluated in vitro. The biological testing results showed that 4-methyl-5-prenyl-8-hydroxy-7-methoxycoumarin (10, IC50 = 28.58 μmol/L) displayed stronger activity than the positive control drug cis-Platin (IC50 = 41.25 μmol/L), which is worthy of further study.