红景天苷元酪醇衍生物的合成及抑菌活性研究

Synthesis and antibacterial activity of rhodiola aglycone tyrosol derivatives

合成两个系列共11个红景天苷元酪醇衍生物,同时对其抑菌活性及构效关系进行了初步探讨。以红景天苷元酪醇为先导化合物,通过Mannich、溴代、氨基化反应等方法对酪醇进行结构修饰,在酪醇的酚羟基邻位引入含N基团,或用溴原子、含N基团取代酪醇的醇羟基,制得目标产物。通过FT-IR、^(1)H NMR、^(13)C NMR和HR-ESI-MS等结构分析对其构效关系进行初步探讨。采用微孔板法测定酪醇及其衍生物的MIC值,以MIC值考察酪醇及其衍生物的抗菌能力。抑菌活性实验显示化合物1对大肠杆菌的抑制能力最佳,其MIC值为0.5 mg·mL^(-1);化合物8、10和11对枯草芽孢杆菌的抑制能力均为最佳,其MIC值为0.125 mg·mL^(-1),化合物8对金黄色葡萄球菌抑制能力最佳,其MIC值为0.0625 mg·mL^(-1)。所合成的11个酪醇衍生物呈现不同强度的抑菌活性,均强于酪醇,但弱于阳性对照物氨苄西林。在红景天苷元酪醇的酚羟基邻位引入含N基团,或用溴原子、含N基团取代红景天苷元酪醇的醇羟基,均可增强其抑菌活性。

Eleven rhodiola aglycone tyrosol derivatives in two series were synthesized,and their antibacterial activity and structure-activity relationship were discussed.Rhodiola aglycone tyrosol was used as the lead compound,and the structure of tyrosol was modified by Mannich,bromination,amination reaction,etc.The N-containing group was introduced at the ortho position of the phenolic hydroxyl group of tyrosol,or bromine atom and N-containing group replaced the alcoholic hydroxyl group of tyrosol to obtain the target product.The structure-activity relationship was preliminarily discussed through structural analysis such as FT-IR,^(1)H NMR,^(13)C NMR and HR-ESI-MS.The microplate method was used to determine the MIC value of tyrosol and its derivatives,and the MIC value was used to investigate their antibacterial ability.The antibacterial activity experiment showed that compound 1 had the best inhibitory ability against E.coli,and its MIC value was 0.5 mg·mL^(-1);compounds 8,10 and 11 had the best inhibitory ability against Bacillus subtilis,and their MIC value were 0.125 mg·mL^(-1),compound 8 had the best inhibitory ability against Staphylococcus aureus,and its MIC value was 0.0625 mg·mL^(-1).The 11 tyrosol derivatives synthesized showed different intensities of antibacterial activity,all of them were stronger than tyrosol,but weaker than the positive control ampicillin.The introduction of N-containing groups into the ortho position of the phenolic hydroxyl group of Rhodiola aglycone tyrosol,or the replacement of the alcoholic hydroxyl group of rhodiola aglycone aglycone tyrosol with bromine atoms or N-containing groups could enhance its antibacterial activity.