白桦脂酸衍生物的合成修饰及其抗菌活性研究

A study on synthesis and antibacterial activity of betulinic acid derivatives

目的:设计白桦脂酸(BA)的新型衍生物结构,研究其及衍生物的体外抗菌活性。方法:通过Jones氧化反应、Claisen Schmidt缩合反应等得到目标化合物BA-01;采用96孔板的琼脂稀释法测定化合物对5种细菌的最小抑菌浓度(MIC)。结果:合成了一种具有新型结构的BA衍生物,且为首次报道的新化合物,其结构通过1H NMR,13C NMR和MS (ESI)等表征分析确定。体外抗菌活性测试结果表明,目标化合物对3种革兰阳性菌均有显著的抑菌活性,其中对金黄色葡萄球菌的抑菌活性最高,其最小抑菌浓度(MIC)为12.5μmol·L^-1,与BA相比显著提高。结论:合成修饰的新型结构中C-3位羟基的修饰以及C-2位上苯环的连接对其生物活性具有重要影响,值得进一步深入探究。

OBJECTIVE To design a novel derivative structure of betulinic acid(BA) and study its in vitro antibacterial activity. METHODS The target compound BA-01 was obtained by Jones oxidation reaction, Claisen Schmidt condensation reaction, etc. The minimum inhibitory concentrations(MIC) of the compound against five bacteria were determined by agar dilution method using a 96-well plate. RESULTS novel structure of BA derivatives was synthesized and the new compound was reported for the first time. Its structure was determined and characterized by 1H NMR, 13C NMR and MS(ESI). The results of in vitro antibacterial activity test showed that the target compound had significant antibacterial activity against three Gram-positive bacteria, among which the antibacterial activity against Staphylococcus aureus was the highest, and the minimum inhibitory concentration(MIC) was 12.5 μmol·L^-1, which was significantly higher than that of BA. CONCLUSION The modification of the hydroxyl group at the C-3 position and the attachment of the benzene ring at the C-2 position in the novel modified structure have an important influence on the biological activity, which deserves to be further investigated.