大黄酰氨基酰胺类衍生物的合成及其抗菌活性

Synthesis and Antibacterial Activity of Rhein Amidoamide Derivatives

为改善大黄酸的理化性质及抗菌活性,对大黄酸结构进行改造。以大黄酸为原料,苯并三氮唑-N,N,N’,N’-四甲基脲六氟磷酸酯(HBTU)为缩合剂、 N,N-二异丙基乙胺(DIPEA)为催化剂,分别与L-脯氨酸甲酯盐酸盐、L-色氨酸甲酯盐酸盐和L-苯丙氨酸甲酯盐酸盐反应,再加入取代苄胺,合成了6个目标化合物4a~4f。利用核磁共振(~1H NMR、^(13)C NMR、^(19)F NMR)及高分辨质谱对目标化合物结构进行确证和表征,并首次探讨了该类化合物对大肠埃希菌、金黄色葡萄球菌、普通变形杆菌的抑菌活性。研究结果表明:部分目标化合物具有较好的抑菌活性,其中化合物4a对金黄色葡萄球菌的最低抑制质量浓度(MIC)值为0.78 mg/L,化合物4e对普通变形杆菌的MIC值为0.39 mg/L,抑菌活性优于大黄酸,甚至优于对照药物氨苄西林。

In order to improve the physicochemical properties and antibacterial activity of rhein,its structure was modified.Using O-benzotriazole-N,N,N′,N′-tetramethylurea(HBTU) as condensing agent,and N,N-diisopropylethylamine(DIPEA) as catalyst,six target compounds(4a-4f) were synthesized by the reaction of rhein with L-proline methyl ester hydrochloride,L-tryptophan methyl ester hydrochloride,L-phenylalanine methyl ester hydrochloride and substituted benzylamine.The structures of the target compounds were confirmed and characterized by(^(1)H,^(13)C,^(19)F) NMR and high-resolution mass spectrometry.The antibacterial activities of these compounds against Escherichia coli,Staphylococcus aureus and Proteus vulgaris were tested for the first time.The results indicated that some of the target compounds had good antibacterial activities,and the minimum inhibitory concentration(MIC) value of compound 4a against S.aureus was 0.78 mg/L,and the MIC value of compound 4e against P.vulgaris was 0.39 mg/L.Their antibacterial activities were better than that of rhein and even better than that of the control drug ampicillin.