富马酸氨基酸酯类衍生物的合成及其抑菌活性研究

本研究以马来酸酐和氨基酸酯为原料,以无水氯化铝为异构化催化剂,经酰胺化、异构化合成了八种富马酸氨基酸酯类衍生物。在以马来酸酐:氨基酸酯:无水氯化铝为0.2 mol:0.2 mol:1.0 g的合成条件下,它们合成的产率均超过75%。经熔点测定和核磁共振氢谱分析对产品的结构进行了确定。通过对大肠杆菌、金黄色葡萄球菌、沙门氏菌、枯草芽孢杆菌、乳酸菌和牛奶酸败混合菌的抑菌活性实验和涂抹皮肤实验,结果表明:富马酸氨基酸酯类衍生物的最低抑菌摩尔浓度与富马酸二甲酯的最低抑菌摩尔浓度相当,但富马酸氨基酸酯类衍生物对人体皮肤没有过敏现象,而富马酸二甲酯具有很强红斑过敏作用。另外还研究了富马酸氨基酸酯类衍生物对正常肝细胞(L02)和肝癌细胞(HepG2)存活率实验,结果发现它们对这两种细胞都没有毒害作用。

Synthesis and Antimicrobial Activity of Fumaric Acid Amino Acid Ester Derivatives

In this study, eight kinds of fumaric acid amino acid ester derivatives were synthesized through amidation and isomerization, by using maleic anhydride and amino acid ester as raw materials and anhydrous aluminium chloride as an isomerization catalyst. Using a ratio of maleic anhydride to amino-acid ester to anhydrous aluminum chloride as 0.2 mol:0.2 mol:1.0 g, the yield of these products was more than 75%. The molecular structure of the compounds was determined by melting point determination and 1H nuclear magnetic resonance imaging. Antimicrobial activity of these compounds against Escherichia coli, Staphylococcus aureus, Salmonella sp., Bacillus subtilis, Lactobacillus sp., bacteria causing milk spoilage, as well as skin smear tests were conducted. The results showed that the minimum inhibitory concentration of fumaric acid amino acid ester derivatives were comparable to that of dimethyl fulminate. Moreover, fumaric acid amino acid ester derivatives did not cause skin allergy, while dimethyl fumarate caused strong skin allergic reactions (red rash). Cell viability of normal liver cells (L02) and hepatoma cells (HepG2) exposed to fumaric acid amino acid ester derivatives was also evaluated, which showed no toxic effect on either cell type.