咖啡酰氨基酸乙酯的合成及其抗氧化活性

Synthesis and Antioxidation of Caffeic Acid Amino Acid Ethyl Ester

摘要:

以L-氨基酸乙酯盐酸盐和咖啡酸为原料，1-(3-二甲基氨基丙基)-3-乙基碳二亚胺盐酸盐（EDC）及1-羟基苯并三唑（HOBt）为催化剂，合成咖啡酰缬氨酸乙酯、咖啡酰亮氨酸乙酯、咖啡酰蛋氨酸乙酯、咖啡酰酪氨酸乙酯4种产物。利用核磁、质谱及红外对产物进行了表征；通过清除DPPH自由基、羟基自由基实验及红细胞溶血等实验分别对咖啡酰氨基酸乙酯类物质的体外抗氧化性活性及刺激性进行了初步评价。结果表明，以此法合成4种咖啡酰氨基酸乙酯，收率在75%～82%。咖啡酸与氨基酸结合后，4种产物均呈现较好的抑制DPPH自由基、羟基自由基活性的效果；咖啡酰缬氨酸乙酯（Ⅲa）清除DPPH自由基能力最强，其IC50为（11.23±0.24）μmol/L；咖啡酰蛋氨酸乙酯（Ⅲc）清除羟基自由基能力最强，其IC50为（0.24 ± 0.002）mmol/L；3种咖啡酰氨基酸乙酯相对于咖啡酸单体对于红细胞膜具有更弱的刺激性。咖啡酰氨基酸乙酯类物质抗氧化活性明显强于L-抗坏血酸（VC），可作为潜在的抗氧化剂。

Abstract:

Caffeyl valine ethyl ester, caffeoyl leucine ethyl ester, caffeoyl methionine ethyl ester, and caffeoyl tyrosine ethyl ester were synthesized by using L-amino acid ethyl ester hydrochloride and caffeic acid as raw materials in the presence of a catalytic amount of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide-hydrochloride (EDC) and 1-hydroxybenzotriene (HOBt) . The structure of the product was identified by mass spectroscopy (MS), nuclear magnetic resonance (1H NMR) and Fourier transform infrared (FTIR) spectroscopies. Then, antioxidant activity and irritation were carefully measured by the DPPH free radicals scavenging, hydroxyl radical scavenging experiments and erythrocyte hemolysis experiments. Four of N-caffeoyl amino acid ethyl esters were synthesized with yields between 75% and 82%. The results showed that after the combination of caffeic acid and amino acid, all the four products showed good inhibition of DPPH free radical and hydroxyl radical activity; caffeoyl valine ethyl ester had the strongest ability to scavenge DPPH free radicals, and its IC50 value was (11.23 ± 0.24) μmol/L; caffeoylmethionine ethyl ester has the strongest ability to scavenge hydroxyl radicals, and its IC50 value is (0.24 ± 0.002) mmol/L. The three caffeoyl amino acid ethyl esters are less irritating to the erythrocyte membrane relative to the caffeic acid monomer. N-caffeoyl amino acid ethyl esters derivatives are more effective than Vitamin C and might serve as new potent antioxidant.