槲皮素酯的合成及清除自由基活性研究
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摘要
以芦丁为原料,利用苄基选择性保护羟基,脱去芦丁糖,再经Williamson反应,脱去苄基,得到槲皮素-3-O-乙酸乙酯,总收率63.8%。IR中ν-OH峰减弱,1737cm~(-1)为乙酸乙酯上的C=O,1660cm-1为C环上4位C=O,νc-o位于1192cm~(-1)、增强;~1H-NMR中槲皮素的3-OH质子峰消失,而在高场出现了三个新峰,分别是:δ4.76ppm为C_3-O-CH_2峰,δ4.12ppm为CH_3-CH_2峰,δ1.17ppm为CH_3峰,说明发生了酯化反应。MS中386.8是槲皮素-3-O-乙酸乙酯的分子离子峰。分别采用邻二氮菲法和DPPH法测定了槲皮素-3-O-乙酸对羟基自由基和DPPH自由基的清除作用,发现槲皮素-3-O-乙酸乙酯较槲皮素具有更强的清除羟基自由基及DPPH自由基活性作用。
The quercetin-3-O-ethyl acetate was synthesized with rutin as raw material by the reactions of the selective protection for the hydroxy groups with benzyl, removing rutinoser, then by the Williamson reaction and removing benzyl, with an overall yield of 63.8%. In FT-IR spectra, the absorption peak of the O-H became weaker, whereas the absorption peak of the C-O located at 1192 cm~(-1) became stronger. In addition, the peak at1737 cm~(-1) indicated the C=O of ethyl acetate and the peak at 1660 cm~(-1) showed the C=O at 4-C of C ring, respectively. The ~1 H-NMR characteriza-tion of the quercetin showed that the 3-OH proton peak disappeared, while three new proton peaks appeared in the high field, including the C_3-OCH_2 peak(4.76 ppm), the CH_3-CH_2 peak(4.12 ppm)as well as the CH_3 peak(1.17 ppm), which indicated that there was an esterification reaction.Moreover, the peak at 386.8 was the molecular ion peak of quercetin-3-O-ethyl acetate in MS. Finally, the scavenging effects of quercetin-3-O-ethyl acetate on OH and DPPH free radicals were determined by O-phenanthroline and DPPH methods respectively. Then it was found that the quercetin-3-O-ethyl acetate had a better scavenging effect on OH and DPPH free radicals.
The quercetin-3-O-ethyl acetate was synthesized with rutin as raw material by the reactions of the selective protection for the hydroxy groups with benzyl, removing rutinoser, then by the Williamson reaction and removing benzyl, with an overall yield of 63.8%. In FT-IR spectra, the absorption peak of the O-H became weaker, whereas the absorption peak of the C-O located at 1192 cm~(-1) became stronger. In addition, the peak at1737 cm~(-1) indicated the C=O of ethyl acetate and the peak at 1660 cm~(-1) showed the C=O at 4-C of C ring, respectively. The ~1 H-NMR characteriza-tion of the quercetin showed that the 3-OH proton peak disappeared, while three new proton peaks appeared in the high field, including the C_3-OCH_2 peak(4.76 ppm), the CH_3-CH_2 peak(4.12 ppm)as well as the CH_3 peak(1.17 ppm), which indicated that there was an esterification reaction.Moreover, the peak at 386.8 was the molecular ion peak of quercetin-3-O-ethyl acetate in MS. Finally, the scavenging effects of quercetin-3-O-ethyl acetate on OH and DPPH free radicals were determined by O-phenanthroline and DPPH methods respectively. Then it was found that the quercetin-3-O-ethyl acetate had a better scavenging effect on OH and DPPH free radicals.
引文
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[2] WEIYOU WANG, CUIXIA SUN, LIKE MAO, et al. The biological activities, chemical stability, metabolism and delivery systems of quercetin:A review[J].Trends Food Sci Tech, 2016,56(1):21~38.
[3] AGNES W BOOTS, GUIDO R M M HAENEN, AALT BAST. Health effects of quercetin:From antioxidant to nutraceutical[J].Eur J Pharmacol, 2008,585(2~3):325~337.
[4] AKIRA M, HITOSHI A, JUNJI T, Multitargeted cancer prevention by quercetin[J].Cancer Letters, 2008,269(2):315~325.
[5] FEDERICO DAJA,LIFE OR DEATH. Neuroprotective And Anticancer Effects Of Quercetin[J].Journal of Ethnopharmacology,2012,143(2):383~396.
[6] DHARAMBIR K,SONAM M,KATRIN S,et al. Molecular mechanisms of action of quercetin in cancer:recent advances[J].Tumor Biol. 2016,37:12927~12939.
[7] ALKA GUPTA, KAVITA BIRHMAN, INDIRA RAHEJA. et al,Quercetin:A wonder bioflavonoid with therapeutic potential in disease management[J].Asian Pac J Trop Med, 2016,6(3):248-252
[8] Manach C, Willoamsoni G, Morand C, et al. Bioavailability and bio-efficacy of polyphenols in humans. I. Review of 97 bioavailability studies[J].Am J Clin Nutrit,2005,81:230~242.
[9] EDISON OSORIO,EDWIN G. P魪REZ,CARLOS ARECHE,et al.Why is quercetin a better antioxidant than taxifolin Theoretical study of mechanisms involving activated forms[J].J Mol Model,2013,19:2165~2172.
[10] FRANCESCA MAININI,ALESSANDRO CONTINI,DONATELLA NAVA,et al.Synthesis, Molecular Characterization and Preliminary Antioxidant Activity Evaluation of Quercetin Fatty Esters[J].J Am Chem Soc,2013,90(10):1751~1759.
[11] WANG XIAO LAN,DUAN YU.Anti-platelet aggregation mechanisms of quercetin fatty acid ester[J].Journal of Chemical and Pharmaceutical Research,2014,6(6):599~602.
[12] SATVIRSL,ZIAULLAHZ,VASANTHAHP,etal.Novelquercetin-3-O-glucoside eicosapentaenoic acid ester,ameliorates inflammation and hyperlipidemia[J].Inflammopharmacology,2015,23:173~185.
[13] FEDORA GRANDE, ORTENSIA I PARISI, ROBERTA A MORDOCCO, et al.Quercetin derivatives as novel antihypertensive agents:Synthesis and physiological characterization[J].EUR J Pharm SCI,2016,82(2):161~170.
[14] KARIMOVA E R, BALTINA L A, SPIRIKHIN L V, et al. Synthesis and antioxidant activity of quercetin ethers[J].Chem Nat Compd, 2015, 51(5):851~855.
[15] RAMESHTHANGAMA P, CHITRA J P.Synergistic anticancer effect of green synthesized nickel nanoparticles and quercetin extracted from Ocimum sanctum leaf extract[J].Journal of Materials Science&Technology,2018, 34(3):508~522.
[16] OSONGA F J, ONYANGO J O, SADIK O A,et al.Synthesis and characterization of novel flavonoid derivatives via sequential phosphorylation of quercetin[J].Tetrahedron Letters, 2017,58:1474~1479.
[17] SAIK A Y H,LIM Y Y,CHOO W S.Enzymatic synthesis of quercetin oleate esters using Candida antarctica lipase B[J].Biotechnol Lett,2017,39:297~304.
[18] SATVIR SEKHON-LOODU,ZIAULLAH ZIAULLAH, VASANTHA RUPASINGHE H P,et al.Novel quercetin-3-O-glucoside eicosapentaenoic acid ester ameliorates inflammation and hyperlipidemia[J]. Inflammopharmacology,2015,23:173~185.
[19] FEDORA GRANDE,ORTENSIA I PARISI,ROBERTA A MORDOCCO,et al.Quercetin derivatives as novel antihypertensive agents:Synthesis and physiological characterization[J].2016,82:161~170.
[20] EKTA KOHLI,HANUMANTHARAO G RAI,RANJU KUMARI,et al.Comparison of the Prevention of Aflatoxin B1-Induced Genotoxicity by Quercetin and Quercetin Pentaacetaten[J].2002,12:2579~2582.
[21] ANIFE AHMEDOVA, KATARZYNA PARADOWSKA, IWONA WAWER. 1H, 13C MAS NMR and DFT GIAO study Of quercetin and its complex with Al(III)in solid state[J]. J Inorg Biochem.,2012,110(1):27~35.
[22] RAVICHANDRAN R,RAJENDRAN M,DEVAPIRIAM D. Structural Characterization And Physicochemical Properties Of Quercetin-Pb Complex[J]. J Coord Chem,2014,67(8):1449~1462.
[23] KIM MIHYANG,PARK YOUNGRONG,CHO SOOYOUNG,et al.Synthesis of alkyl quercetin derivatives,J Korean Soc Appl Biol Chem[J].J Korean Soc Appl Bi,2015,58(3):343~348.
[24] VANESA A M, GABRIELA V F, MATIAS I S, et al. Spectroscopic and Thermodynamic Study of Chrysin and Quercetin Complexes with Cu(II)[J].J. Chem. Eng. Data, 2016,61(2):987~995.
[25] TORU SAITO, TAKASHI KAWAKAMI, SHUSUKE YAMANAKA, et al.Computational Study of Catalytic Reaction of Quercetin2,4-Dioxygenase[J].J. Phys. Chem. B,2015,119(23):6952~6962.