染料木素木糖苷的合成及其生物活性研究
摘要
本论文分为四个部分
第一章：综述了黄酮类化合物糖苷化修饰的研究进展。阐明了本课题的研究意义和方向
第二章：采用相转移催化法合成染料木素木糖苷，对产物进行了IR，~1H NMR，~(13)CNMR，和MS表征。
第三章：分别采用Fenton-邻菲罗啉显色法，邻苯三酚自氧化法和紫外可见分光光度法，考察了BHT、BHA、染料木素及其木糖糖苷清除·OH、·O_2~-、DPPH自由基能力和间接保护羟基自由基损伤DNA能力，结果显示染料木素木糖苷清除能力强于其母体染料木素，并且能保护DNA免受自由基损伤。
第四章：采用紫外，荧光和粘度法考察了染料木素及其木糖苷与小牛胸腺DNA的作用。结果表明，在ctDNA存在下，染料木素及其糖苷均发生了明显的减色反应。另外，受试物均能有效猝灭EB-DNA体系的荧光，并使ctDNA溶液的粘度增大。据此推断，染料木素及其糖苷以部分插入及氢键作用与ctDNA结合。
This paper consists of four parts.
Chapter 1 In this section, advances in glycosidation modification of flavoniods were reviewed. The significance and direction of the research were elucidated.
Chapter 2 The conditions for synthesis and purification of genistein xylosides by phase transfer catalyzed method was investigated, and the structural characterization of target compound was also conducted by IR, ~1H NMR, ~(13)C NMR and MS spectra in this part.
Chapter 3 The abilities of genistein and their derivatives in free radical scavenging of·OH and·O_2~- and DPPH were exploited by using Fenton reaction with O-phenanthroline chromogenic reaction, pyrogallol autoxidation, methodUV-vis spectrophotometry and protective effect of Genistein and its glycoside on hydroxyl radicals mediated DNA damage, respectively. The results show that the abilities of glycoside derivatives of genistein in scavenging of the three free radicals were not obviously improved compared with genistein.And show can prevent DNA damage from hydroxyl radicals.
Chapter 4 The interactions of genistein, genistein xyloside with calf thymus DNA(ctDNA) were investigated in this section by using means of UV spectra, fluorescent spectra and viscosity, respectively. The results showed that the UV spectra of genistein and its glycosides showed obviously hypochromism under the presence of ctDNA. In addition, the tested compounds could make the fluorescence intensity of EB-DNA system decreased sharply, and also increased the relative viscosity of ctDNA aqueous. The experimental results suggested that genistein and its glycosides could bind to ctDNA by combination of partly intercalation and hydrogen bonding mode.
第一章：综述了黄酮类化合物糖苷化修饰的研究进展。阐明了本课题的研究意义和方向
第二章：采用相转移催化法合成染料木素木糖苷，对产物进行了IR，~1H NMR，~(13)CNMR，和MS表征。
第三章：分别采用Fenton-邻菲罗啉显色法，邻苯三酚自氧化法和紫外可见分光光度法，考察了BHT、BHA、染料木素及其木糖糖苷清除·OH、·O_2~-、DPPH自由基能力和间接保护羟基自由基损伤DNA能力，结果显示染料木素木糖苷清除能力强于其母体染料木素，并且能保护DNA免受自由基损伤。
第四章：采用紫外，荧光和粘度法考察了染料木素及其木糖苷与小牛胸腺DNA的作用。结果表明，在ctDNA存在下，染料木素及其糖苷均发生了明显的减色反应。另外，受试物均能有效猝灭EB-DNA体系的荧光，并使ctDNA溶液的粘度增大。据此推断，染料木素及其糖苷以部分插入及氢键作用与ctDNA结合。
This paper consists of four parts.
Chapter 1 In this section, advances in glycosidation modification of flavoniods were reviewed. The significance and direction of the research were elucidated.
Chapter 2 The conditions for synthesis and purification of genistein xylosides by phase transfer catalyzed method was investigated, and the structural characterization of target compound was also conducted by IR, ~1H NMR, ~(13)C NMR and MS spectra in this part.
Chapter 3 The abilities of genistein and their derivatives in free radical scavenging of·OH and·O_2~- and DPPH were exploited by using Fenton reaction with O-phenanthroline chromogenic reaction, pyrogallol autoxidation, methodUV-vis spectrophotometry and protective effect of Genistein and its glycoside on hydroxyl radicals mediated DNA damage, respectively. The results show that the abilities of glycoside derivatives of genistein in scavenging of the three free radicals were not obviously improved compared with genistein.And show can prevent DNA damage from hydroxyl radicals.
Chapter 4 The interactions of genistein, genistein xyloside with calf thymus DNA(ctDNA) were investigated in this section by using means of UV spectra, fluorescent spectra and viscosity, respectively. The results showed that the UV spectra of genistein and its glycosides showed obviously hypochromism under the presence of ctDNA. In addition, the tested compounds could make the fluorescence intensity of EB-DNA system decreased sharply, and also increased the relative viscosity of ctDNA aqueous. The experimental results suggested that genistein and its glycosides could bind to ctDNA by combination of partly intercalation and hydrogen bonding mode.
引文
[1] 曹鸿志，李祖义．生物催化在非天然寡糖合成中的应用[J]．有机化学，2002，22(1)：11-22．
[2] 王超杰，宋金勇，赵瑾．二元酸茄呢醇乳糖和麦芽糖糖酯合成及生理活性测试研究[J]．有机化学，2003，23(10)：1102-1106．
[3] 付新梅，江涛，王奎旗等．糖类对先导化合物的化学修饰及其在药学中的应用[J]．中国海洋药物，2001，3，54—62．
[4] 赵晶，张致平，陈鸿珊，等．黄芩甙衍生物的合成及抗人免疫缺陷病毒活性研究．药学学报，1998，33(1)：22-27
[5] 高慧媛，隋安丽，陈艺虹，等．中药黄独的化学成分．沈阳药科大学学报，2003，3：178-180
[6] Ferté J, Kiihnel J M, Chapuis G, et al. Flavonoid-related modulators of multidrug resistance: synthesis, pharmacological activity, and structure-activity relationships. J. Med. Chem., 1999, 42:478-489
[7] Graf B A, Mullen W, Caldwell S T, et al. Disposition and metabolism of [2-~(14)C] quercetin-4'-glucoside in rats. Drug Metabolism and Disposition, 2005, 33:1036-1043
[8] Lim S S, Jung S H, Ji J, et al. synthesis of flavonoids and their effects on aldose reductase and sorbitol accumulation in streptozotocin-induced diabetic rat tissues. Journal of Pharmacy and Pharmacology, 2001, 53:653-668
[9] 唐于平，楼凤昌，马雯，等．槐果皮中的异黄酮甙类成分．中国药科大学学报，2001，32(3)：187-189
[10] Lee C H, Yang L, Xu Z J, et al. Relative antioxidant activity of soybean isoflavones and their glycosides. Food Chemistry, 2005, 90:735-741
[11] Harborne，JB．等著，戴伦凯，谢玉如等译．黄酮类化合物．科学出版社，1983，336
[12] Costas D., Alexios L.,et al. Phase-transfer catalyzed synthesis of flavonoid glycosides Carbohydr. Res. 1990, 207:131—137
[13] 刘丽娟，刘银燕，杨晓红．葱属植物苗体化合物及黄酮化合物的研究进展中国药学杂志，2000，35(6)：367-370
[14] 刘丽娟，王秀坤，付起凤等．长瓣金莲花的抑菌作用及其总黄酮的含量测定 中草药，1992，23(9)：461
[15] Stuart T. Caldwell,Alan Crozierb, Richard C.Hartley. Isotopic Labelling of Quercetin 4'-O-β-D-Glucoside[J]. Tetrahedron,2000, 56:4101-4106
[16] Takumi Furuta, Tomoyuki Kimura, Sachiko Kondo.Concise total synthesis of flavone C-glycoside having potent anti-inflammatory activity[J].Tetrahedron, 2004,60:9375-9379
[17] Toshihiro Kumazawa,Takayuki Kimura,Shigeru Matsuba. Synthesis of 8-C-glucosylflavones[J]. Carbohydrate Research, 2001,334:183-193.
[18] 徐鲁斌，罗爱民，曹正白．黄酮-4′-O-糖苷的合成[J]．苏州大学学报，2003，19(2)：95-100
[19] 孙昌俊，王义贵，胡为峰等．糖苷合成研究(V)2-O-院基-5-氟脲嘧啶-O-葡萄糖醛酸苷的合成及其抗肿瘤活性研究[J]．合成化学．1994，2(3)：246-250．
[20] 孙昌俊，孙义，王义贵等．糖苷合成研究(Ⅶ)——芳磺酰基氟脲嘧啶糖苷的合成及其抗肿瘤活性研究[J]．山东大学学报，1997，32(4)：443-447．
[21] Laurent F. Bomaghi, Sally-Ann Poulsen . Microwave-accelerated Fischer glycosylation[J]. Tetrahedron Letters ,2005,46:3485-3488
[22] Juan Manuel Juárez Ruiz, Gerd Oβwald, Michael Petersen. The "Natural Strategy"for the glycosidase-assisted synthesis of simple glycosides[J]. Journal of Molecular Catalysis B: Enzymatic, 2001,11:189-197
[23] Costas Demetzos, Alexios-Leandros Skaltsounis, Francois Tillequin. Phase-transfer-catalyzed synthesis of flavonoid glycosides[J].Carbohydrnte Research, 1990,207: 131-I37
[24] 孙昌俊，王义贵，李洪祥等．糖苷合成研究(Ⅺ)2-取代氟脲嘧啶β-D-乙酰基木糖苷类化合物的合成及其抗肿瘤活性[J]．中国药物化学杂志，1997，7(2)：84-87
[25] 孙昌俊，戚聿新，李爱霞等．糖苷合成研究(ⅪⅤ)2-烷氧基(2-苯硫基)-5-氟-3H-4-嘧啶酮木糖的合成及其抗肿瘤活性研究[J]．中国药物化学杂志，1999，9(4)：245-249．
[26] Kin-ichi Oyama,Tadao Kondo. Total synthesis of apigenin 7,4'-di-O-b-glucopyranoside,a component of blue flower pigment of Salvia patens,and seven chiral analogues[J]. Tetrahedron, 2004,60: 2025-2034.
[27] 李润涛，王永富，朱茜．相转移催化法在糖苷化反应中的应用[J]．化学通报，1999，3：6-11
[28] 李雯，罗德林，刘宏民．葡萄糖香草醛的相转移催化合成法[J]．河南科学，1999，17(3)：250-253．
[29] 陈勇，韩国防，刘惠英．相转移催化法合成糖苷化合物[J]．化学研究与应用，2005，17(4)：501-503．
[30] Suoding Cao, Francois D.Tropper, René Roy: Stereoselective Phase Transfer Catalyzed Syntheses of Glycosyloxysuccinimides and their Transformations into Glycoprobes[J]. Tetrahedron,1995,51(24): 6679-6686.
[31] D. Carrière, S.J. Meunier, F.D. Tropper. Phase transfer catalysis toward the synthesis of O-, S-, Se- and C-glycosides[J]. Journal of Molecular Catalysis A: Chemical, 2000,154:9-22
[32] Denis Giguére,Sachiko Sato,Christian St-Pierre.Aryl O- and S-galactosides and lactosides as specific inhibitors of human galectins-1 and -3: Role of electrostatic potential at O-3 [J]. Bioorganic & Medicinal Chemistry Letters,2006,16: 1668-1672.
[33] Ming Li,Xiuwen Han,Biao Yub.Synthesis of quercetin 3-O-(2″-galloyl)-a-L-arabinopyranoside [J] Tetrahedron Letters, 2002,43:9467-9470
[34] Lewis P, Kaltia S, Wahala K. J. Chem. Soc. Perkin Trans, 1998, 1:2481-2484
[35] Lewis P T, Wahala K. Tetrahedron Letters, 1998, 39:9559-9562
[36] 任欣意，杨斌，张宝龙．芒柄花素7-O-葡萄糖苷的合成研究[J]．天津化工，2006，20(2)19-20
[37] 余燕影，胡昕，曹树稳．染料木素7，4′-二-β-D-吡喃葡萄糖苷的合成[J]．化学研究与应用，2007，19(3)：323-326．．
[38] 宋国辉，邓泽元，曹树稳等。染料木素7，4′-二-β-D-吡喃乳糖苷的合成及表征[J]．化学试剂，2007，29(8)：449-451．
[39] Yuguo Du, Guohua Wei,Robert J.Linhardt. The first total synthesis of calabricoside A [J]. Tetrahedron Letters,2003,44:6887-6890
[40] Ming Li,Xiuwen Han, Biao Yu. Facile Synthesis of Flavonoid 7-O-Glycosides[J]. J. Org. Chem, 2003,68(17): 6842-6845.
[41] 朱运平，江正强，李里特，等．烷基木糖苷的酶法合成及其纯化．过程工程学报，2004，4(6)：572-576
[42] 孙家莉，褚婕，丁晓琴．酶底物对硝基苯-a-D吡喃葡糖苷的合成．化学试剂，2005，27(2)，97-98
[43] Kren V, Ulrichová J, Kosina P, et al. Chemoenzymaticpreparation of silybin b-glucuronides and their biological evaluation. Drug Metabolism And Disposition, 2000, 28 (12):1513-1517
[44] Kadereit D, Waldmann H. Enzymatic protecting group techniques. Chem. Rew., 2001, 101: 3367-3396
[45] 姜忠义．天然产物分子结构的酶催化修饰改性。化学通报，2002，65：1-7
[46] Barnes S. Effect of genistein on in vitro and in vivo models of cancer[J]. Nutr ,1995,125(3) :777 - 783.
[47] 刘颖，张牧，王小雪等．染料木黄酮对人体胃癌细胞生长仰制作用研究[J]．营养学报，2001，23(1)，62-65．
[48] 张涛，迟晓星，韩俊等．染料木素对前列腺癌细胞恶性增殖的抑制作用[J]．中国公共卫生，2006，22(12)：1414-1416．
[49] Hwang J L, Hodis H N, Sevanian A. Soy and alfalfa phytoestrogen extracts become potent low-density lipoprotein antioxidants in the presence of acerola cherry extract. J. Agric. Food Chem, 2001, 49 (1): 308-314
[50] Lamartiniere C A, Protection against breast cancer with genistein: a component of soy. Am J Clin Nutr, 2000, 71 (6): 1705S-1707S
[51] Kang J L, Lee H W, Kim H J, et al. Inhibition of SRC tyrosine kinases suppresses activation of nuclear factor-kappaB, and serine and tyrosine phosphorylation of lkappaB-alpha in lipopolysaccharide-stimulated raw 264.7 macrophages. J Toxicol Environ, Health, 2005, 68: 1643-1662
[52] Krzysztof P, Joanna P, Piotr K, et al. Cytostatic and cytotoxic activity of synthetic genistein glycosides against human cancer cell lines. Cancer Letters, 2004, 203:59-69
[53] 阎祥华，顾景范，孙存普．大豆异黄酮的抗癌作用机制研究进展．生理科学进展，1997，28(4)：362-364
[54] Jesper Malmberg, Katrin Mani, Elinawén et al. Synthesis of aromatic C-xylosides by position invertion of glucose. Bioorg. Med. Chem. 2006, 14:6659-6665
[55] 孙昌俊，王义贵，李洪祥等，糖苷合成研究(Ⅺ)2-取代氟尿嘧啶β-D-乙酰基木糖苷类化合物的合成及其抗肿瘤活性。中国药物化学杂志，1996，7(2)84-87
[1] Barnes S. Effect of genistein on in vitro and in vivo models of cancer[J]. Nutr ,1995,125(3) :777-783.
[2] 刘颖，张牧，王小雪等．染料木黄酮对人体胃癌细胞生长抑制作用研究[J]．营养学报，2001，23(1)，62-65．
[3] 张涛，迟晓星，韩俊等．染料木素对前列腺癌细胞恶性增殖的抑制作用[J]．中国公共卫生，2006，22(12)：1414-1416．
[4] Harborne J．B．等著，戴伦凯，谢玉如等译．黄酮类化合物．科学出版社，1983，336
[5] Costas D., Alexios L., et al. Phase-transfer catalyzed synthesis of flavonoid glycosides Carbohydr. Res. 1990, 207:131—137
[6] 刘丽娟，刘银燕，杨晓红．葱属植物苗体化合物及黄酮化合物的研究进展 中国药学杂志，2000，35(6)：367-370
[7] 马磊，楼凤昌．槐角中的抗癌活性成分．中国天然药物，2006，4(2)：151-153
[8] 唐于平，楼凤昌，马雯，等．槐果皮中的异黄酮甙类成分．中国药科大学学报，2001，32(3)：187-189
[9] 王景华，李明慧，王亚琳，等．槐种子化学成分研究(Ⅱ)．中草药，2002，33(7)：586-588
[10] 刘丽娟，王秀坤，付起凤等．长辦金莲花的抑菌作用及其总黄酮的含量测定 中草药，1992，23(9)：461
[11] Jesper Malmberg, Katrin Mani, Elinawén et al. Synthesis of aromatic C-xylosides by position invertion of glucose. Bioorg. Med. Chem. 2006, 14:6659-6665
[12] 孙昌俊，王义贵，李洪祥等，糖苷合成研究(Ⅺ)2-取代氟尿嘧啶β-D-乙酰基木糖苷类化合物的合成及其抗肿瘤活性。中国药物化学杂志，1996，7(2)84-87
[13] Hudson CS , Jonuson JM. The isomeric tetracetates of xylose ,and observation regarding the acetates of melibiose treholose and sucrose. J Am Chem Sci ,1915,37 (3) :2748～2753
[14] 王克军，李化军，赵毅民．天然黄酮苷的合成研究进展．化学通报，2005，7：490-496
[15] Philip Lewis, Seppo Kaltia, Kristiina Wahala. The phase transfer catalysed synthesis of isoflavone-O-glucosides. J. Chem. Soc., Perkin Trans, 1998, 1:2481-2484
[16] Philip T. Lewis, Kfistiina Wahala. Regiispecific 4'-O-β-glucosidation of isoflavone. Tetrahedron Letters,1998, 39:9559-9562
[17] Philip T.Lewis, Kfistiina Wahala, Antti Hoikkala ,et al .Synthesis of antioxidant isoflavone fatty acid esters. Tetrahedron,2000, 56:7805-7810
[18] 徐任生主编．天然产物化学[M]．科学出版社．2004．553-554．
[19] 王克军，李化军，赵毅民．天然黄酮苷的合成研究进展．化学通报，2005，7：490-496
[20] Philip T. Lewis, Kdstiina Wahala. Regiispecific 4'-O-β-glucosidation of isoflavone.Tetrahedron Letters,1998, 39:9559-9562
[21] Philip T.Lewis, Kristiina Wahala, Antti Hoikkala , et al .Synthesis of antioxidant isoflavone fatty acid esters. Tetrahedron,2000, 56:7805-7810
[1] Marian V, Dieter L, Jan M, et al. Free radicals and antioxidants in normal physiological functions and human disease. IJBCB, 2007, 39:44-84
[2] Yasser FMK, Hanan MAA. Free-radical scavenging and antioxidative activities of some polysaccharides in emulsions. LWT, 2007, 40:270-277
[3] 郑荣梁．自由基生物学．北京：高等教育出版社，1992．
[4] Axel K, Hans L, Edda K.Alternative pathways as mechanism for the negative effects associated with overexperoxide dismutase.J Theor Bio,2006,238:828-840
[5] Cao G H ,Sofic E,Prior R L,Antioxidant and prooxidant behavior of flavonoids :structure-activity relationship.Free Radical Bio&Medicine,1997,22(5):749-760
[6] Manuel P, Lara M, Mafia JN, et al. Solvent effect on quercetin antioxidant capacity. Food Chemistry, 2004, 88:201-207
[7] Richard AD, Daneel F. Molecules of Interest Genistein, Phytochemistry, 2002, 60:205-211
[8] Jacek Z ,Jerzy G, Graegorz G. Radical scavenging properties of genistein .Free Radical Bio&Medicine,2003,35(8):958-965
[9] Jacques F, Kuhnel J M,Chapuis G. Flavonoid-related modulators of multidrug resistance :synthesis,pharmacologic activity, and steucture-activity relationship.J Medchem, 1999,42,478-489
[10] Zhang H Y ,Wang L F ,Sun Y M ,Why B-ring is the activity center for genistein to scavenge peroxyl radical:A DET study .Bioorganic &Medicinal Chemistry Letters,2003,12:909-911
[11] Chung HL, Lin Y, Jin ZX, et al. Relative antioxidant activity of soybean isoflavones and their glycosides. Food Chemistry, 2005, 90:735-741
[12] 覃事栋，冯思思，张红梅，等．配合物[Ni(EDTB)]．2Cl·CH_3OH·C2H_5OH的合成、晶体结构及SOD模拟活性的研究。化学学报，2005，63(13)：1155-1160
[13] 刘建文，季光，魏东芝。药理实验方法学，北京：化学工业出版社，2003，97-98
[14] Douglas D. Buechter .Free radical and oxygen toxicity.Pharmaceutical research ,1988,5:253
[15] Ozcan Erel.A novel automated methord to measure total antioxidant response against potent free radical reations .Clinical Biochemistry ,2004(37):112
[16] 静天玉，赵晓渝。用终止剂改进超氧化物歧化酶邻苯三酚测活性．生物化学与生物物理进展，1995，22(1)：84-86
[17] 袁斌，高若梅，邻苯三酚自氧化反应的动力学研究。高等化学学报，1997，18(9)：1438-1441
[18] 梁毅，屈松生，汪存信，等。微量热法研究超氧化物歧化酶反应。中国科学(B)，1998，28 (4)：361-370
[19] Mecocci P, Fano G, Fulle S,etal.Age-dependent increase in oxidative damage to DNA,lipid sand proteins in human skeletal muscle[J].Free Radic Biol Med,1999,26:303.
[20] Longwen, PhyllisE,BowenDB.Diet modification affect DNA oxidative damage in healthy humans[J].Free Radic Biol Meal,1999,26:695.
[21] LubecG.The OH Radical from chemistry to human disease[J].J Invest Meal,1996,44:324.
[22] Duthie S,Collins AR.The influence of cell growth detoxifying enzymes and DNA repair on H_2O_2 mediated DNA damage in human cells[J].Free Radic Biol Meal,1997,22:717.
[23] Mistry N,Mark DE,Helen RG, etal.Immunochemical detection of glyoxal DNA damage[J].Free Radic Biol Med,1999,26:1267.
[24] 张红雨．黄酮类抗氧化剂结构-活性关系的理论解释。中国科学(B辑)，1999，29(1)：91-96
[25] 胡春，丁霄霖。黄酮类化合物在不同氧化体系中的抗氧化作用研究。食品与发酵工业，1996，3：46-53
[1] 张礼和．以核酸为作用靶的药物研究．北京大学学报(医学版)，2002，34(5)：418-426
[2] 张容颖，庞代文，蔡汝秀．DNA与其靶向分子相互作用研究进展．高等化学学报，1999，20(8)：1210-1217
[3] 杨频，宋宇飞．金属配合物键合DNA的研究进展．化学进展，2000，12(1)：32-40
[4] 韦捷敏，田华，王麟生．抗癌金属配合物的研究进展．化学世界，2003，11：602-605
[5] Kelloff G J, Growell J A, Hank E J, et al. Strategy and planning for chemopreventive drug development:clinical development plans Ⅱ. J Cell Biochem, 1996, 26:54-71
[6] Richard A D, Daneel F. Genistein. Phytochem, 2002, 60(3): 205-211
[7] Barnes S, Kim H, Victor D, et al. Beyond ER alpha and ER beta: estrogen receptor binding is only part of the isoflavone story J. Nutr, 2000, 130:656S-657
[8] Lamartiniere C A. Protection against breast cancer with genistein : a component of soy. Am J Clin Nutr, 2000, 71(6): 1705S-1707S
[9] Hwang J L, Hodis H N, Sevanian A. Soy and alfalfa phytestrogen extracts become potent low-density lipoprotein antioxidants in the presence of acerola cherry extract. J Agric Food. Chem, 2001, 49(1): 308-314
[10] Kang J L, Lee H W, Kim H J, et al. Inhibition of SRC tyrosine kinases suppresses activation of nuclear factor-kappaB, and serine and tyrosine phosphorylation of lkappaB-alpha in lipopolysaccharide-stimulated raw 264.7 macrophages. J Toxicol Environ, Health, 2005, 68: 1643-1662
[11] 金永生，刘超美，吴秋业，等．新型金雀异黄素衍生物5-羟基-4′-硝基-7-取代酰氧基异黄酮的合成及抗肿瘤活性研究．第二军医大学学报，2005，26(2)：182-185
[12] Alessandra R, Venera C, Laura L, et al. Genistin inhibits UV light-induced plasmid DNA damage and cell growth in human melanoma cell. J Nutr Biochem, 2006, 17(2):103-108
[13] Suk H K, Myung J K, Jin S H, et al. Comparison of oral bioavailability of genistein and genistin in rats. Int J Pharmaceut, 2007, doi: 10.1016/j.ijpharm.2006.12.046
[14] 唐于平，楼凤昌，马雯，等．槐果皮中的异黄酮甙类成分．中国药科大学学报，2001，32(3)：187-189
[15] Joanna P, Krzysztof P, Janusz S S, et al. In vitro toxicity evaluation in the development of new anticancer drugs-genistein glycosides. Cancer Letters, 2005, 229:67-75
[16] 刘彩红，李红，李洪清，等．Cu(phen)22+与6-羟基嘌呤及DNA的相互作用．化学通报，2005．9：702-708
[17] 郭玉华，陈晓岚，张婷，等．7-羟基黄酮及磷酰化7-羟基黄酮与DNA的弱相互作用荧光法研究．光谱学与光谱分析，2006，26(3)：475-479
[18] 周庆华，杨频．1,3-双(2-苯并咪唑基)-2-氧杂丙烷与锌配合物的合成、晶体结构及其与DNA作用方式的研究．光谱化学学报，2006，64(8)：793-798
[19] 王平红，张岐，袁文兵，等．鬼臼酰肼金属Ni(Ⅱ)，Co(Ⅱ)，Zn(Ⅱ)配合物与DNA分子作用机制的研究．光谱学与光谱分析，2006，26(7)：1298-1302
[20] 高恩君，赵淑敏，刘祁涛，等．三元配合物钯(Ⅲ)-联喹啉-丙二酸根的合成及其生物活性研究．化学学报，2004，62：593-597
[21] Usha S, Johnson I M, Malathi R. Modulation of DNA intercalation by resveratrol and genistein. Mol.Cell.Biochem, 2006, 284:57-64
[22] Chao H, Mei W J, Huang Q W, et al. J Inorg. Biochem, 2002, 92:165-170
[24] 李来生，黄伟东，王瑞琼，等．荧光法研究抗癌药物更生霉素D与小牛胸腺DNA的作用机理．化学学报，1999，57：572-577
[25] 雷英杰，杨易成，史小凤．抗癌活性天然化合物金雀异黄酮的量子化学研究．天津理工大学学报，2006，22(3)：52-54
[26] Usha S, Johnson I M, Malathi R. Interaction of resveratrol and genistein with nucleic acids. J Biochem Mol Biol, 2005, 38(2): 198-205
[27] 张剑，张高勇，谢克昌，等．可改变DNA构象的非离子糖基表面活性剂．化学学报，2003，61(10)：1658-1663
[2] 王超杰，宋金勇，赵瑾．二元酸茄呢醇乳糖和麦芽糖糖酯合成及生理活性测试研究[J]．有机化学，2003，23(10)：1102-1106．
[3] 付新梅，江涛，王奎旗等．糖类对先导化合物的化学修饰及其在药学中的应用[J]．中国海洋药物，2001，3，54—62．
[4] 赵晶，张致平，陈鸿珊，等．黄芩甙衍生物的合成及抗人免疫缺陷病毒活性研究．药学学报，1998，33(1)：22-27
[5] 高慧媛，隋安丽，陈艺虹，等．中药黄独的化学成分．沈阳药科大学学报，2003，3：178-180
[6] Ferté J, Kiihnel J M, Chapuis G, et al. Flavonoid-related modulators of multidrug resistance: synthesis, pharmacological activity, and structure-activity relationships. J. Med. Chem., 1999, 42:478-489
[7] Graf B A, Mullen W, Caldwell S T, et al. Disposition and metabolism of [2-~(14)C] quercetin-4'-glucoside in rats. Drug Metabolism and Disposition, 2005, 33:1036-1043
[8] Lim S S, Jung S H, Ji J, et al. synthesis of flavonoids and their effects on aldose reductase and sorbitol accumulation in streptozotocin-induced diabetic rat tissues. Journal of Pharmacy and Pharmacology, 2001, 53:653-668
[9] 唐于平，楼凤昌，马雯，等．槐果皮中的异黄酮甙类成分．中国药科大学学报，2001，32(3)：187-189
[10] Lee C H, Yang L, Xu Z J, et al. Relative antioxidant activity of soybean isoflavones and their glycosides. Food Chemistry, 2005, 90:735-741
[11] Harborne，JB．等著，戴伦凯，谢玉如等译．黄酮类化合物．科学出版社，1983，336
[12] Costas D., Alexios L.,et al. Phase-transfer catalyzed synthesis of flavonoid glycosides Carbohydr. Res. 1990, 207:131—137
[13] 刘丽娟，刘银燕，杨晓红．葱属植物苗体化合物及黄酮化合物的研究进展中国药学杂志，2000，35(6)：367-370
[14] 刘丽娟，王秀坤，付起凤等．长瓣金莲花的抑菌作用及其总黄酮的含量测定 中草药，1992，23(9)：461
[15] Stuart T. Caldwell,Alan Crozierb, Richard C.Hartley. Isotopic Labelling of Quercetin 4'-O-β-D-Glucoside[J]. Tetrahedron,2000, 56:4101-4106
[16] Takumi Furuta, Tomoyuki Kimura, Sachiko Kondo.Concise total synthesis of flavone C-glycoside having potent anti-inflammatory activity[J].Tetrahedron, 2004,60:9375-9379
[17] Toshihiro Kumazawa,Takayuki Kimura,Shigeru Matsuba. Synthesis of 8-C-glucosylflavones[J]. Carbohydrate Research, 2001,334:183-193.
[18] 徐鲁斌，罗爱民，曹正白．黄酮-4′-O-糖苷的合成[J]．苏州大学学报，2003，19(2)：95-100
[19] 孙昌俊，王义贵，胡为峰等．糖苷合成研究(V)2-O-院基-5-氟脲嘧啶-O-葡萄糖醛酸苷的合成及其抗肿瘤活性研究[J]．合成化学．1994，2(3)：246-250．
[20] 孙昌俊，孙义，王义贵等．糖苷合成研究(Ⅶ)——芳磺酰基氟脲嘧啶糖苷的合成及其抗肿瘤活性研究[J]．山东大学学报，1997，32(4)：443-447．
[21] Laurent F. Bomaghi, Sally-Ann Poulsen . Microwave-accelerated Fischer glycosylation[J]. Tetrahedron Letters ,2005,46:3485-3488
[22] Juan Manuel Juárez Ruiz, Gerd Oβwald, Michael Petersen. The "Natural Strategy"for the glycosidase-assisted synthesis of simple glycosides[J]. Journal of Molecular Catalysis B: Enzymatic, 2001,11:189-197
[23] Costas Demetzos, Alexios-Leandros Skaltsounis, Francois Tillequin. Phase-transfer-catalyzed synthesis of flavonoid glycosides[J].Carbohydrnte Research, 1990,207: 131-I37
[24] 孙昌俊，王义贵，李洪祥等．糖苷合成研究(Ⅺ)2-取代氟脲嘧啶β-D-乙酰基木糖苷类化合物的合成及其抗肿瘤活性[J]．中国药物化学杂志，1997，7(2)：84-87
[25] 孙昌俊，戚聿新，李爱霞等．糖苷合成研究(ⅪⅤ)2-烷氧基(2-苯硫基)-5-氟-3H-4-嘧啶酮木糖的合成及其抗肿瘤活性研究[J]．中国药物化学杂志，1999，9(4)：245-249．
[26] Kin-ichi Oyama,Tadao Kondo. Total synthesis of apigenin 7,4'-di-O-b-glucopyranoside,a component of blue flower pigment of Salvia patens,and seven chiral analogues[J]. Tetrahedron, 2004,60: 2025-2034.
[27] 李润涛，王永富，朱茜．相转移催化法在糖苷化反应中的应用[J]．化学通报，1999，3：6-11
[28] 李雯，罗德林，刘宏民．葡萄糖香草醛的相转移催化合成法[J]．河南科学，1999，17(3)：250-253．
[29] 陈勇，韩国防，刘惠英．相转移催化法合成糖苷化合物[J]．化学研究与应用，2005，17(4)：501-503．
[30] Suoding Cao, Francois D.Tropper, René Roy: Stereoselective Phase Transfer Catalyzed Syntheses of Glycosyloxysuccinimides and their Transformations into Glycoprobes[J]. Tetrahedron,1995,51(24): 6679-6686.
[31] D. Carrière, S.J. Meunier, F.D. Tropper. Phase transfer catalysis toward the synthesis of O-, S-, Se- and C-glycosides[J]. Journal of Molecular Catalysis A: Chemical, 2000,154:9-22
[32] Denis Giguére,Sachiko Sato,Christian St-Pierre.Aryl O- and S-galactosides and lactosides as specific inhibitors of human galectins-1 and -3: Role of electrostatic potential at O-3 [J]. Bioorganic & Medicinal Chemistry Letters,2006,16: 1668-1672.
[33] Ming Li,Xiuwen Han,Biao Yub.Synthesis of quercetin 3-O-(2″-galloyl)-a-L-arabinopyranoside [J] Tetrahedron Letters, 2002,43:9467-9470
[34] Lewis P, Kaltia S, Wahala K. J. Chem. Soc. Perkin Trans, 1998, 1:2481-2484
[35] Lewis P T, Wahala K. Tetrahedron Letters, 1998, 39:9559-9562
[36] 任欣意，杨斌，张宝龙．芒柄花素7-O-葡萄糖苷的合成研究[J]．天津化工，2006，20(2)19-20
[37] 余燕影，胡昕，曹树稳．染料木素7，4′-二-β-D-吡喃葡萄糖苷的合成[J]．化学研究与应用，2007，19(3)：323-326．．
[38] 宋国辉，邓泽元，曹树稳等。染料木素7，4′-二-β-D-吡喃乳糖苷的合成及表征[J]．化学试剂，2007，29(8)：449-451．
[39] Yuguo Du, Guohua Wei,Robert J.Linhardt. The first total synthesis of calabricoside A [J]. Tetrahedron Letters,2003,44:6887-6890
[40] Ming Li,Xiuwen Han, Biao Yu. Facile Synthesis of Flavonoid 7-O-Glycosides[J]. J. Org. Chem, 2003,68(17): 6842-6845.
[41] 朱运平，江正强，李里特，等．烷基木糖苷的酶法合成及其纯化．过程工程学报，2004，4(6)：572-576
[42] 孙家莉，褚婕，丁晓琴．酶底物对硝基苯-a-D吡喃葡糖苷的合成．化学试剂，2005，27(2)，97-98
[43] Kren V, Ulrichová J, Kosina P, et al. Chemoenzymaticpreparation of silybin b-glucuronides and their biological evaluation. Drug Metabolism And Disposition, 2000, 28 (12):1513-1517
[44] Kadereit D, Waldmann H. Enzymatic protecting group techniques. Chem. Rew., 2001, 101: 3367-3396
[45] 姜忠义．天然产物分子结构的酶催化修饰改性。化学通报，2002，65：1-7
[46] Barnes S. Effect of genistein on in vitro and in vivo models of cancer[J]. Nutr ,1995,125(3) :777 - 783.
[47] 刘颖，张牧，王小雪等．染料木黄酮对人体胃癌细胞生长仰制作用研究[J]．营养学报，2001，23(1)，62-65．
[48] 张涛，迟晓星，韩俊等．染料木素对前列腺癌细胞恶性增殖的抑制作用[J]．中国公共卫生，2006，22(12)：1414-1416．
[49] Hwang J L, Hodis H N, Sevanian A. Soy and alfalfa phytoestrogen extracts become potent low-density lipoprotein antioxidants in the presence of acerola cherry extract. J. Agric. Food Chem, 2001, 49 (1): 308-314
[50] Lamartiniere C A, Protection against breast cancer with genistein: a component of soy. Am J Clin Nutr, 2000, 71 (6): 1705S-1707S
[51] Kang J L, Lee H W, Kim H J, et al. Inhibition of SRC tyrosine kinases suppresses activation of nuclear factor-kappaB, and serine and tyrosine phosphorylation of lkappaB-alpha in lipopolysaccharide-stimulated raw 264.7 macrophages. J Toxicol Environ, Health, 2005, 68: 1643-1662
[52] Krzysztof P, Joanna P, Piotr K, et al. Cytostatic and cytotoxic activity of synthetic genistein glycosides against human cancer cell lines. Cancer Letters, 2004, 203:59-69
[53] 阎祥华，顾景范，孙存普．大豆异黄酮的抗癌作用机制研究进展．生理科学进展，1997，28(4)：362-364
[54] Jesper Malmberg, Katrin Mani, Elinawén et al. Synthesis of aromatic C-xylosides by position invertion of glucose. Bioorg. Med. Chem. 2006, 14:6659-6665
[55] 孙昌俊，王义贵，李洪祥等，糖苷合成研究(Ⅺ)2-取代氟尿嘧啶β-D-乙酰基木糖苷类化合物的合成及其抗肿瘤活性。中国药物化学杂志，1996，7(2)84-87
[1] Barnes S. Effect of genistein on in vitro and in vivo models of cancer[J]. Nutr ,1995,125(3) :777-783.
[2] 刘颖，张牧，王小雪等．染料木黄酮对人体胃癌细胞生长抑制作用研究[J]．营养学报，2001，23(1)，62-65．
[3] 张涛，迟晓星，韩俊等．染料木素对前列腺癌细胞恶性增殖的抑制作用[J]．中国公共卫生，2006，22(12)：1414-1416．
[4] Harborne J．B．等著，戴伦凯，谢玉如等译．黄酮类化合物．科学出版社，1983，336
[5] Costas D., Alexios L., et al. Phase-transfer catalyzed synthesis of flavonoid glycosides Carbohydr. Res. 1990, 207:131—137
[6] 刘丽娟，刘银燕，杨晓红．葱属植物苗体化合物及黄酮化合物的研究进展 中国药学杂志，2000，35(6)：367-370
[7] 马磊，楼凤昌．槐角中的抗癌活性成分．中国天然药物，2006，4(2)：151-153
[8] 唐于平，楼凤昌，马雯，等．槐果皮中的异黄酮甙类成分．中国药科大学学报，2001，32(3)：187-189
[9] 王景华，李明慧，王亚琳，等．槐种子化学成分研究(Ⅱ)．中草药，2002，33(7)：586-588
[10] 刘丽娟，王秀坤，付起凤等．长辦金莲花的抑菌作用及其总黄酮的含量测定 中草药，1992，23(9)：461
[11] Jesper Malmberg, Katrin Mani, Elinawén et al. Synthesis of aromatic C-xylosides by position invertion of glucose. Bioorg. Med. Chem. 2006, 14:6659-6665
[12] 孙昌俊，王义贵，李洪祥等，糖苷合成研究(Ⅺ)2-取代氟尿嘧啶β-D-乙酰基木糖苷类化合物的合成及其抗肿瘤活性。中国药物化学杂志，1996，7(2)84-87
[13] Hudson CS , Jonuson JM. The isomeric tetracetates of xylose ,and observation regarding the acetates of melibiose treholose and sucrose. J Am Chem Sci ,1915,37 (3) :2748～2753
[14] 王克军，李化军，赵毅民．天然黄酮苷的合成研究进展．化学通报，2005，7：490-496
[15] Philip Lewis, Seppo Kaltia, Kristiina Wahala. The phase transfer catalysed synthesis of isoflavone-O-glucosides. J. Chem. Soc., Perkin Trans, 1998, 1:2481-2484
[16] Philip T. Lewis, Kfistiina Wahala. Regiispecific 4'-O-β-glucosidation of isoflavone. Tetrahedron Letters,1998, 39:9559-9562
[17] Philip T.Lewis, Kfistiina Wahala, Antti Hoikkala ,et al .Synthesis of antioxidant isoflavone fatty acid esters. Tetrahedron,2000, 56:7805-7810
[18] 徐任生主编．天然产物化学[M]．科学出版社．2004．553-554．
[19] 王克军，李化军，赵毅民．天然黄酮苷的合成研究进展．化学通报，2005，7：490-496
[20] Philip T. Lewis, Kdstiina Wahala. Regiispecific 4'-O-β-glucosidation of isoflavone.Tetrahedron Letters,1998, 39:9559-9562
[21] Philip T.Lewis, Kristiina Wahala, Antti Hoikkala , et al .Synthesis of antioxidant isoflavone fatty acid esters. Tetrahedron,2000, 56:7805-7810
[1] Marian V, Dieter L, Jan M, et al. Free radicals and antioxidants in normal physiological functions and human disease. IJBCB, 2007, 39:44-84
[2] Yasser FMK, Hanan MAA. Free-radical scavenging and antioxidative activities of some polysaccharides in emulsions. LWT, 2007, 40:270-277
[3] 郑荣梁．自由基生物学．北京：高等教育出版社，1992．
[4] Axel K, Hans L, Edda K.Alternative pathways as mechanism for the negative effects associated with overexperoxide dismutase.J Theor Bio,2006,238:828-840
[5] Cao G H ,Sofic E,Prior R L,Antioxidant and prooxidant behavior of flavonoids :structure-activity relationship.Free Radical Bio&Medicine,1997,22(5):749-760
[6] Manuel P, Lara M, Mafia JN, et al. Solvent effect on quercetin antioxidant capacity. Food Chemistry, 2004, 88:201-207
[7] Richard AD, Daneel F. Molecules of Interest Genistein, Phytochemistry, 2002, 60:205-211
[8] Jacek Z ,Jerzy G, Graegorz G. Radical scavenging properties of genistein .Free Radical Bio&Medicine,2003,35(8):958-965
[9] Jacques F, Kuhnel J M,Chapuis G. Flavonoid-related modulators of multidrug resistance :synthesis,pharmacologic activity, and steucture-activity relationship.J Medchem, 1999,42,478-489
[10] Zhang H Y ,Wang L F ,Sun Y M ,Why B-ring is the activity center for genistein to scavenge peroxyl radical:A DET study .Bioorganic &Medicinal Chemistry Letters,2003,12:909-911
[11] Chung HL, Lin Y, Jin ZX, et al. Relative antioxidant activity of soybean isoflavones and their glycosides. Food Chemistry, 2005, 90:735-741
[12] 覃事栋，冯思思，张红梅，等．配合物[Ni(EDTB)]．2Cl·CH_3OH·C2H_5OH的合成、晶体结构及SOD模拟活性的研究。化学学报，2005，63(13)：1155-1160
[13] 刘建文，季光，魏东芝。药理实验方法学，北京：化学工业出版社，2003，97-98
[14] Douglas D. Buechter .Free radical and oxygen toxicity.Pharmaceutical research ,1988,5:253
[15] Ozcan Erel.A novel automated methord to measure total antioxidant response against potent free radical reations .Clinical Biochemistry ,2004(37):112
[16] 静天玉，赵晓渝。用终止剂改进超氧化物歧化酶邻苯三酚测活性．生物化学与生物物理进展，1995，22(1)：84-86
[17] 袁斌，高若梅，邻苯三酚自氧化反应的动力学研究。高等化学学报，1997，18(9)：1438-1441
[18] 梁毅，屈松生，汪存信，等。微量热法研究超氧化物歧化酶反应。中国科学(B)，1998，28 (4)：361-370
[19] Mecocci P, Fano G, Fulle S,etal.Age-dependent increase in oxidative damage to DNA,lipid sand proteins in human skeletal muscle[J].Free Radic Biol Med,1999,26:303.
[20] Longwen, PhyllisE,BowenDB.Diet modification affect DNA oxidative damage in healthy humans[J].Free Radic Biol Meal,1999,26:695.
[21] LubecG.The OH Radical from chemistry to human disease[J].J Invest Meal,1996,44:324.
[22] Duthie S,Collins AR.The influence of cell growth detoxifying enzymes and DNA repair on H_2O_2 mediated DNA damage in human cells[J].Free Radic Biol Meal,1997,22:717.
[23] Mistry N,Mark DE,Helen RG, etal.Immunochemical detection of glyoxal DNA damage[J].Free Radic Biol Med,1999,26:1267.
[24] 张红雨．黄酮类抗氧化剂结构-活性关系的理论解释。中国科学(B辑)，1999，29(1)：91-96
[25] 胡春，丁霄霖。黄酮类化合物在不同氧化体系中的抗氧化作用研究。食品与发酵工业，1996，3：46-53
[1] 张礼和．以核酸为作用靶的药物研究．北京大学学报(医学版)，2002，34(5)：418-426
[2] 张容颖，庞代文，蔡汝秀．DNA与其靶向分子相互作用研究进展．高等化学学报，1999，20(8)：1210-1217
[3] 杨频，宋宇飞．金属配合物键合DNA的研究进展．化学进展，2000，12(1)：32-40
[4] 韦捷敏，田华，王麟生．抗癌金属配合物的研究进展．化学世界，2003，11：602-605
[5] Kelloff G J, Growell J A, Hank E J, et al. Strategy and planning for chemopreventive drug development:clinical development plans Ⅱ. J Cell Biochem, 1996, 26:54-71
[6] Richard A D, Daneel F. Genistein. Phytochem, 2002, 60(3): 205-211
[7] Barnes S, Kim H, Victor D, et al. Beyond ER alpha and ER beta: estrogen receptor binding is only part of the isoflavone story J. Nutr, 2000, 130:656S-657
[8] Lamartiniere C A. Protection against breast cancer with genistein : a component of soy. Am J Clin Nutr, 2000, 71(6): 1705S-1707S
[9] Hwang J L, Hodis H N, Sevanian A. Soy and alfalfa phytestrogen extracts become potent low-density lipoprotein antioxidants in the presence of acerola cherry extract. J Agric Food. Chem, 2001, 49(1): 308-314
[10] Kang J L, Lee H W, Kim H J, et al. Inhibition of SRC tyrosine kinases suppresses activation of nuclear factor-kappaB, and serine and tyrosine phosphorylation of lkappaB-alpha in lipopolysaccharide-stimulated raw 264.7 macrophages. J Toxicol Environ, Health, 2005, 68: 1643-1662
[11] 金永生，刘超美，吴秋业，等．新型金雀异黄素衍生物5-羟基-4′-硝基-7-取代酰氧基异黄酮的合成及抗肿瘤活性研究．第二军医大学学报，2005，26(2)：182-185
[12] Alessandra R, Venera C, Laura L, et al. Genistin inhibits UV light-induced plasmid DNA damage and cell growth in human melanoma cell. J Nutr Biochem, 2006, 17(2):103-108
[13] Suk H K, Myung J K, Jin S H, et al. Comparison of oral bioavailability of genistein and genistin in rats. Int J Pharmaceut, 2007, doi: 10.1016/j.ijpharm.2006.12.046
[14] 唐于平，楼凤昌，马雯，等．槐果皮中的异黄酮甙类成分．中国药科大学学报，2001，32(3)：187-189
[15] Joanna P, Krzysztof P, Janusz S S, et al. In vitro toxicity evaluation in the development of new anticancer drugs-genistein glycosides. Cancer Letters, 2005, 229:67-75
[16] 刘彩红，李红，李洪清，等．Cu(phen)22+与6-羟基嘌呤及DNA的相互作用．化学通报，2005．9：702-708
[17] 郭玉华，陈晓岚，张婷，等．7-羟基黄酮及磷酰化7-羟基黄酮与DNA的弱相互作用荧光法研究．光谱学与光谱分析，2006，26(3)：475-479
[18] 周庆华，杨频．1,3-双(2-苯并咪唑基)-2-氧杂丙烷与锌配合物的合成、晶体结构及其与DNA作用方式的研究．光谱化学学报，2006，64(8)：793-798
[19] 王平红，张岐，袁文兵，等．鬼臼酰肼金属Ni(Ⅱ)，Co(Ⅱ)，Zn(Ⅱ)配合物与DNA分子作用机制的研究．光谱学与光谱分析，2006，26(7)：1298-1302
[20] 高恩君，赵淑敏，刘祁涛，等．三元配合物钯(Ⅲ)-联喹啉-丙二酸根的合成及其生物活性研究．化学学报，2004，62：593-597
[21] Usha S, Johnson I M, Malathi R. Modulation of DNA intercalation by resveratrol and genistein. Mol.Cell.Biochem, 2006, 284:57-64
[22] Chao H, Mei W J, Huang Q W, et al. J Inorg. Biochem, 2002, 92:165-170
[24] 李来生，黄伟东，王瑞琼，等．荧光法研究抗癌药物更生霉素D与小牛胸腺DNA的作用机理．化学学报，1999，57：572-577
[25] 雷英杰，杨易成，史小凤．抗癌活性天然化合物金雀异黄酮的量子化学研究．天津理工大学学报，2006，22(3)：52-54
[26] Usha S, Johnson I M, Malathi R. Interaction of resveratrol and genistein with nucleic acids. J Biochem Mol Biol, 2005, 38(2): 198-205
[27] 张剑，张高勇，谢克昌，等．可改变DNA构象的非离子糖基表面活性剂．化学学报，2003，61(10)：1658-1663