普那霉素ⅡA类似物的制备与体外活性测定

Separation,preparation and in vitro activity assay of pristinamycin ⅡA analogues

目的:分离制备普那霉素ⅡA类似物,进行结构鉴定与体外活性测定。方法:采用液相色谱法对普那霉素ⅡA粗品中的类似物进行分离纯化,通过核磁共振波谱和质谱进行结构解析,并采用枯草芽孢杆菌考察其体外抗菌活性。结果:分离得到4个类似物,分别鉴定为13-羟基-普那霉素ⅡA、20-去甲基-普那霉素ⅡA、2-去甲基-普那霉素ⅡA、18,28-二氢-普那霉素ⅡA(普那霉素ⅡB),对枯草芽孢杆菌均有一定的抗菌活性,且与普那霉素IA有明显的协同作用,但都不及普那霉素ⅡA与普那霉素IA协同作用强。结论:分离得到的4个类似物与普那霉素ⅡA骨架结构基本一致,属同系列化合物,其13位C=O是主要活性位点。本研究为普那霉素的质量控制与系统研究提供有意义的参考。

Objective: To separate and prepare pristinamycin ⅡA analogues and carry out structural identification and in vitro activity determination.Methods: Liquid chromatography was adopted to separate and purify the pristinamycin ⅡA analogues,and nuclear magnetic resonance spectrum and mass spectrum analysis were used to identify the structures,then the antibacterial activity of Bacillus subtilis in vitro was investigated.Results:Four analogues were isolated and identified as 13-hydroxy-pristinamycin ⅡA,20-demethyl-pristinamycin ⅡA,2-demethyl-pristinamycin ⅡA,18,28-dihydro-pristinamycin ⅡA (pristinamycin ⅡB),which had certain antibacterial activity and strong synergistic effect with pristinamycin IA,but no one was better than pristinamycin ⅡA.Conclusion:The skeletal structures of the four compounds are consistent with pristinamycin ⅡA,which belong to the same series of compounds,and the C = O (C-13) groups may be the main active site.This study provided meaningful reference for the quality control and further research of pristinamycin.