槲皮素-3-氧-酰基酯的合成及其生物活性
摘要
槲皮素是一种具有多种生物活性的黄酮类化合物。以槲皮素为先导物,选择性地对C环3位羟基进行结构修饰。以廉价的芦丁为原料,经苄基化保护、酸水解得到中间体1(7,3',4'-氧-三苄基槲皮素),中间体1与羧酸发生Steglich酯化反应,再经Pd/C催化加氢脱苄基得到7种槲皮素-3-氧-酰基酯,目标产物结构经红外光谱(IR)、1H核磁共振(NMR)、13C NMR、电喷雾-质谱(ESI-MS)确证。采用邻二氮菲法和DPPH法考查7种目标化合物的抗氧化活性,结果显示,槲皮素3位羟基以2~3个碳原子的羧酸取代能提高其抗氧化活性。采用MTT法初步评价了7种目标化合物对人食管癌细胞(EC109)、人食管鳞癌细胞(EC9706)、人胃癌细胞(MGC-803)和人前列腺癌细胞(PC-3)的抑制作用。结果表明,槲皮素3位羟基以7个碳原子以上羧酸取代能显著提高其对MGC-803细胞的抑制作用。
引文
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[3]SULTANA B,ANWAR F.Flavonols(kaempeferol,quercetin,myricetin)contents of selected fruits,vegetables and medicinal plants[J].Food Chemistry,2008,108(3):879-884.
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[6]BOOTS A W,HAENEN G R M M,BAST A.Health effects of quercetin:from antioxidant to nutraceutical[J].European Journal of Pharmacology,2008,585(2):325-337.
[7]KHOO N K H,WHITE C R,POZZO-MILLER L,et al.Dietary flavonoid quercetin stimulates vasorelaxation in aortic vessels[J].Free Radical Biology and Medicine,2010,49(3):339-347.
[8]LARSON A J,SYMONS J D,JALILI T.Quercetin:a treatment for hypertension:a review of efficacy and mechanisms[J].Pharmaceuticals,2010,3(1):237-250.
[9]MURAKAMI A,ASHIDA H,TERAO J.Multitargeted cancer prevention by quercetin[J].Cancer Letters,2008,269(2):315-325.
[10]DAJAS F.Life or death:neuroprotective and anticancer effects of quercetin[J].Journal of Ethnopharmacology,2012,143(2):383-396.
[11]MENDOZA E E,BURD R.Quercetin as a systemicchemopreventative agent:structural and functional mechanisms[J].Mini Reviews in Medicinal Chemistry,2011,11(14):1216-1221.
[12]VARGAS A J,BURD R.Hormesis and synergy:pathways and mechanisms of quercetin in cancer prevention and management[J].Nutrition Reviews,2010,68(7):418-428.
[13]朱玮,翟广玉,樊卫华,等.槲皮素酯类衍生物的研究进展[J].化学与黏合,2011,33(6):67-71,79.
[14]DOMINGO L R,AURELL M J,PREZ P,et al.Quantitative characterization of the local electrophilicity of organic molecules.Understanding the regioselectivity on Diels-Alder Reactions[J].The Journal of Physical Chemistry A,2002,106(29):6871-6875.
[15]SAIJA A,TOMAINO A,TROMBETTA D,et al.‘In vitro’antioxidant and photoprotective properties and interaction with model membranes of three new quercetin esters[J].European Journal of Pharmaceutics and Biopharmaceutics,2003,56(2):167-174.
[16]GATTO M T,FALCOCCHIO S,GRIPPA E,et al.Antimicrobial and anti-lipase activity of quercetin and its C2-C16 3-O-acyl-esters[J].Bioorganic&Medicinal Chemistry,2002,10(2):269-272.
[17]MONTENEGRO L,CARBONE C,MANISCALCO C,et al.In vitro evaluation of quercetin-3-O-acyl esters as topical prodrugs[J].International Journal of Pharmaceutics,2007,336(2):257-262.
[18]THAPA M,KIM Y,DESPER J,et al.Synthesis and antiviral activity of substituted quercetins[J].Bioorganic&Medicinal Chemistry Letters,2012,22(1):353-356.
[19]JACOB J K,TIWARI K,CORREA-BETANZO J,et al.Biochemical basis for functional ingredient design from fruits[J].Annual Review of Food Science and Technology,2012,3:79-104.
[20]HUANG H,JIA Q,MA J,et al.Discovering novel quercetin-3-O-amino acid-esters as a new class of Src tyrosine kinase inhibitors[J].European Journal of Medicinal Chemistry,2009,44(5):1982-1988.
[21]FRAISSE D,HEITZ A,CARNAT A,et al.Quercetin 3-arabinopyranoside,a major flavonoid compound from Alchemilla xanthochlora[J].Fitoterapia,2000,71(4):463-464.
[22]王俏,邹阳,钟耕,等.多酚类单体物质抗氧化活性的研究[J].食品工业科技,2011(1):137-140.
[23]DEHGHAN G,KHOSHKAM Z.Tin(II)-quercetin complex:synthesis,spectral characterisation and antioxidant activity[J].Food Chemistry,2012,131(2):422-426.
[24]李化军,栾新慧,赵毅民.3-O-甲基槲皮素的合成[J].有机化学,2004,24(12):1619-1621.
[25]陈志卫,胡永洲.四种天然槲皮素-3-糖苷的合成[J].有机化学,2006,26(6):813-816.
[26]LEE J,MITCHELL A E.Quercetin and isorhamnetin glycosides in onion(Allium cepa L.):varietal comparison,physical distribution,coproduct evaluation,and long-term storage stability[J].Journal of Agricultural and Food Chemistry,2011,59(3):857-863.