大黄酸衍生物的合成及其抑菌活性研究

Synthesis and Antibacterial Activity of Derivatives of Rhein

以大黄酸(1)为先导化合物,在对羧基酰胺化的基础上,再对蒽醌母核C7位进行结构修饰,合成了系列大黄酸衍生物,同时对其抑菌活性及构效关系进行了初步探讨。FT-IR、1H NMR、13C NMR和MS等结构分析表明,大黄酸衍生物分别为:大黄酸哌啶酰胺(2)、7-羟甲基-大黄酸哌啶酰胺(3)、7-溴甲基-大黄酸哌啶酰胺(4)、7-(4-吗啉基)甲基-大黄酸哌啶酰胺(5a)、7-(1-四氢吡咯)甲基-大黄酸哌啶酰胺(5b)和7-(1-甲基-4-哌嗪)甲基-大黄酸哌啶酰胺(5c)。抑菌活性实验结果表明:化合物5a和5b对大肠杆菌的最小抑菌质量浓度(MIC)值分别达到了0.78和0.39 mg/L,抑菌活性明显优于大黄酸(MIC值为3.13 mg/L),甚至强于阳性对照物卡那霉素(MIC值为1.56 mg/L);同时5a对金黄色葡萄球菌的MIC值也达到了1.56 mg/L,与大黄酸相当。初步的构效关系分析表明:在大黄酸蒽醌母核的C7位取代基上引入未取代杂环可增强对大肠杆菌的抑制作用。

Based on carboxyl amidation of rhein（ 1）,a series of derivatives of rhein were synthesized by structure modification of C7 of anthraquinone mother nucleus. And the antibacterial activity and structure-activity relationship of the derivatives were preliminary discussed. The derivatives of rhein were respectively rhein piperidine amide（ 2）,7-hydroxymethyl-rhein piperidine amide（ 3）,7-bromomethyl-rhein piperidine amide（ 4）,7-（ 4-morpholino） methyl-rhein piperidine amide（ 5 a）,7-（ pyrrolidin-1-yl） methyl-rhein piperidine amide（ 5 b）,7-（ 1-methyl-4-piperazinyl） methyl-rhein piperidine amide（ 5 c）. The structures of the compounds were characterized by IR,^1H NMR,^13C NMR,MS. The minimal inhibitory concentrations（ MIC） of the compounds obtained were tested and the MIC of compounds 5 a and 5 b against E. coli reached 0. 78 and 0. 39 mg/L respectively. Their antibacterial activity were stronger than that of rhein（ MIC 3.13 mg/L） obviously,even stronger than that of the kanamycin（ MIC1.56 mg/L）; and the MIC of compound 5 a against S. aureus reached 1. 56 mg/L,which was similar to that of rhein. The preliminary analysis of structure effective relationship showed that if none replace heterocyclic groups were introduced into substituent of C7 of the mother nucleus,the antibaterial activity on E.coli would be stronger.