咖啡酰氨基酸乙酯的合成及其抗氧化活性
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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~1HNMR、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活性及刺激性进行了初步评价。结果表明,以该法合成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IC_(50)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IC_(50)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。
Caffeylvaline ethyl ester, caffeoylleucine ethyl ester, caffeoyl methionine ethyl ester, and caffeoyl tyrosine ethyl ester were synthesized from L-amino acid ethyl ester hydrochloride with caffeic acid in the presence of a catalytic amount of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride(EDC)and 1-hydroxybenzotrizole(HOBt). Their structures were identified by mass spectroscopy(MS), proton nuclear magnetic resonance(~1HNMR) and Fourier transform infrared(FTIR) spectroscopy. Then, their antioxidant activities and irritation were measured by the scavenging capability to DPPH and hydroxyl free radicals, as well as erythrocyte hemolysis experiment. The results showed that four N-caffeoyl amino acid ethyl esters were synthesized with yields between 75% and 82%. After the combination of caffeic acid and amino acid, all products exhibited good inhibition effects against DPPH free radical and hydroxyl radical.Among them, caffeoylvaline ethyl ester(Ⅲa) had the strongest ability to scavenge DPPH free radical, and its IC_(50) value was(11.23±0.24) μmol/L. Caffeoylmethionine ethyl ester(Ⅲc) had the strongest ability to scavenge hydroxyl free radical with an IC_(50) value of(0.24±0.002) mmol/L. Three synthesized caffeoyl amino acid ethyl esters were less irritating to the erythrocyte membrane than caffeic acid monomer. The antioxidant activities of N-caffeoyl amino acid ethyl esters derivatives were more effective than Vitamin C and could be used as a new potent antioxidant.
Caffeylvaline ethyl ester, caffeoylleucine ethyl ester, caffeoyl methionine ethyl ester, and caffeoyl tyrosine ethyl ester were synthesized from L-amino acid ethyl ester hydrochloride with caffeic acid in the presence of a catalytic amount of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride(EDC)and 1-hydroxybenzotrizole(HOBt). Their structures were identified by mass spectroscopy(MS), proton nuclear magnetic resonance(~1HNMR) and Fourier transform infrared(FTIR) spectroscopy. Then, their antioxidant activities and irritation were measured by the scavenging capability to DPPH and hydroxyl free radicals, as well as erythrocyte hemolysis experiment. The results showed that four N-caffeoyl amino acid ethyl esters were synthesized with yields between 75% and 82%. After the combination of caffeic acid and amino acid, all products exhibited good inhibition effects against DPPH free radical and hydroxyl radical.Among them, caffeoylvaline ethyl ester(Ⅲa) had the strongest ability to scavenge DPPH free radical, and its IC_(50) value was(11.23±0.24) μmol/L. Caffeoylmethionine ethyl ester(Ⅲc) had the strongest ability to scavenge hydroxyl free radical with an IC_(50) value of(0.24±0.002) mmol/L. Three synthesized caffeoyl amino acid ethyl esters were less irritating to the erythrocyte membrane than caffeic acid monomer. The antioxidant activities of N-caffeoyl amino acid ethyl esters derivatives were more effective than Vitamin C and could be used as a new potent antioxidant.
引文
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[3]Mattila P,Hellstr M J,Trrnen R.Phenolic acids in berries,fruits,and beverages[J].Journal of Agricultural&Food Chemistry,2006,54(19):7193-7199.
[4]Sun Y,Yu Y Y,Cao S W.Antioxidant capacity of caffeicacid,phloretin and glutathione mixtures and formula optimization[J].Asian Journal of Chemistry,2013,25(7):3971-3978.
[5]Jiang R W,Lau K M,Hon P M,et al.Chemistry and biological activities of caffeic acid derivatives from salvia miltiorrhiza[J].Current Medicinal Chemistry,2005,12(2):237-246.
[6]Wei Q Y,Jiang H,Zhang J X,et al.Synthesis of N-hydroxycinnamoylamino acid ester analogues and their free radical scavenging and antioxidative activities[J].Medicinal Chemistry Research,2012,21(8):1905-1911.
[7]Rajan P,Vedernikova I,Cos P,et al.Synthesis and evaluation of caffeic acid amides as antioxidants[J].Bioorganic&Medicinal Chemistry Letters,2001,11(2):215-217.
[8]Yoo Y J,Nam D H,Jung S Y,et al.Synthesis of cinnamoylketoamides as hybrid structures of antioxidants and calpain inhibitors[J].Bioorganic&Medicinal Chemistry Letters,2011,21(10):2850-2854.
[9]Karau A,Grayson I.Amino acids in human and animal nutrition[J].Advances in Biochemical Engineering,2014,143:189-228.
[10]Furneri P M,Piperno A,Sajia A,et al.Antimycoplasmal activity of hydroxytyrosol[J].Antimicrobial Agents&Chemotherapy,2004,48(12):4892-4894.
[11]Noh J M,Kwak S Y,Seo H S,et al.Kojic acid-amino acid conjugates as tyrosinase inhibitors[J].Bioorganic&Medicinal Chemistry Letters,2009,19(19):5586-5589.
[12]Anselmi C,Centini M,Andreassi M,et al.Conformational analysis:a tool for the elucidation of the antioxidant properties of ferulic acid derivatives in membrane models[J].Journal of Pharmaceutical&Biomedical Analysis,2004,35(5):1241-1249.
[13]Boath A S,Stewart D,Mcdougall G J.Berry components inhibitα-glucosidase in vitro:synergies between acarbose and polyphenols from black currant and rowanberry[J].Food Chemistry,2012,135(3):929-936.
[14]Fan Q,Jiang H,Yuan E D,et al.Tyrosinase inhibitory effects and antioxidative activities of novel cinnamoyl amides with amino acid ester moiety[J].Food Chemistry,2012,134(2):1081-1087.
[15]Treml J,?mejkal K.Flavonoids as potent scavengers of hydroxyl radicals[J].Comprehensive Reviews in Food Science&Food Safety,2016,15(4):720-738.
[16]Zhang Wengai(张文改),Yang Xingfen(杨杏芬),Yang Ying(杨颖),et al.Preliminary study on red blood cell haemolysis assay as an alternative method for eye irritation test[J].Chin Prev Med(中国预防医学杂志),2010,11(6):544-547.
[17]Wang Yufeng(王羽峰),Cheng Jun(成军).Effect of leucine on membrane potential of sputum oocytes and its mechanism[J].Heilongjiang Medical Science(黑龙江医药科学),1989,12(1):1-4.