（5，14）-二十碳二炔-1-四氢吡喃醚的合成研究
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摘要
环氧-二十碳三烯酸(EETs)在心血管系统中有多种重要的生物学功能,国外学者研究发现14,15-环氧二十碳-5-(Z)-烯酸(14,15-EE-5-ZE)能特异性地拮抗由EET诱导的血管舒张,并且对血管增生具有抑制作用,因此我们推测其能应用于肿瘤的治疗。本文设计了14,15-EE-5-ZE的前体化合物(5,14)-二十碳二炔-1-四氢吡喃醚的合成路线,对其合成进行了详细的研究。
以1,7-庚二醇为起始原料,用氢溴酸将其溴代,得到7-溴-1-庚醇。用2,3-二氢吡喃保护7-溴-1-庚醇的羟基,得到7-溴-1-庚醇的四氢吡喃醚,将其与1-庚炔进行偶连,得到8-十四炔-1-四氢吡喃醚。以PPTs为催化剂,脱除8-十四炔-1-四氢吡喃醚的羟基保护基,得到8-十四炔-1-醇。用四溴化碳和三苯基磷作为溴代试剂将8-十四炔-1-醇溴代,得到1-溴-8-十四炔。另外用2,3-二氢吡喃保护5-己炔-1-醇的羟基,得到5-己炔-1-四氢吡喃醚。最后将5-己炔-1-四氢吡喃醚与1-溴-8-十四炔进行偶连,得到产物(5,14)-二十碳二炔-1-四氢吡喃醚。实验总收率14.5%。
我们做了如下创新:设计了(5,14)-二十碳二炔-1-四氢吡喃醚新的合成路线;首次研究了1,7-庚二醇的单溴代反应的反应溶剂、反应温度、反应时间、反应物摩尔比等因素对产率的影响;对端位炔烃与溴代烷的偶连反应的无水无氧实验方法进行了设计和改进,缩短了反应时间,使产物易于分离提纯。
产物用硅胶柱层析分离提纯,并用红外光谱、氢核磁共振谱及质谱验证了产物的结构。结果表明合成路线完全可行。
Cytochrome P-450 metabolites, including the epoxyeicosatrienoic acids (EETs) which play an important role in the system of heart vein. In the recent years, a 14,15-EET analogue, (14,15)-epoxyeicosa-5(Z)-enoic acid (14,15-EE-5-ZE) was synthesized and identified as an EET-specific antagonist. In our work, we designed and researched the synthesis route of a key intermediate (5,14)-eicosadiyne-1-tetrahydropyran and synthesized it.
1,7-heptadiol, the starting material, reacted with hydrobromic acid to produce 7-bromheptane-1-ol, which hydroxy was protected by 2,3-dihydropyran . Then, it coupled with the heptaalkyne. The coupling product was taken off the 2,3-dihydropyran at the extremity, and the alcohol we obtained was brominated with CBr4 and PPh3, furnishing a new bromide (a). Next, the hydroxy of 5-hexyne-1-ol was protected by 2,3-dihydropyran with the catalytic reaction of PPTs. Alkylation of the protected alkyne, using bromide (a), produced the bis-acetylene. The total yield was 14.5%.
Some innovations we did as following: firstly, we designed a new synthesis route of (5,14)-eicosadiyne-1-tetrahydropyran; secondly, we studied the bromination reaction influence factors of 1,7-heptadiol in detail, including reaction time、reaction temperature、solvent dosage、reagent mole ratio; thirdly, we discussed the mechanism of 1-alkyne coupled with mono-bromide, and optimized the reaction condition.
We utilized silica gel column chromatography to separate and purify product, and applied infrared spectrum、1H NMR and mass spectrum to testify product structure. The final result indicated that our synthesis route was feasible.
以1,7-庚二醇为起始原料,用氢溴酸将其溴代,得到7-溴-1-庚醇。用2,3-二氢吡喃保护7-溴-1-庚醇的羟基,得到7-溴-1-庚醇的四氢吡喃醚,将其与1-庚炔进行偶连,得到8-十四炔-1-四氢吡喃醚。以PPTs为催化剂,脱除8-十四炔-1-四氢吡喃醚的羟基保护基,得到8-十四炔-1-醇。用四溴化碳和三苯基磷作为溴代试剂将8-十四炔-1-醇溴代,得到1-溴-8-十四炔。另外用2,3-二氢吡喃保护5-己炔-1-醇的羟基,得到5-己炔-1-四氢吡喃醚。最后将5-己炔-1-四氢吡喃醚与1-溴-8-十四炔进行偶连,得到产物(5,14)-二十碳二炔-1-四氢吡喃醚。实验总收率14.5%。
我们做了如下创新:设计了(5,14)-二十碳二炔-1-四氢吡喃醚新的合成路线;首次研究了1,7-庚二醇的单溴代反应的反应溶剂、反应温度、反应时间、反应物摩尔比等因素对产率的影响;对端位炔烃与溴代烷的偶连反应的无水无氧实验方法进行了设计和改进,缩短了反应时间,使产物易于分离提纯。
产物用硅胶柱层析分离提纯,并用红外光谱、氢核磁共振谱及质谱验证了产物的结构。结果表明合成路线完全可行。
Cytochrome P-450 metabolites, including the epoxyeicosatrienoic acids (EETs) which play an important role in the system of heart vein. In the recent years, a 14,15-EET analogue, (14,15)-epoxyeicosa-5(Z)-enoic acid (14,15-EE-5-ZE) was synthesized and identified as an EET-specific antagonist. In our work, we designed and researched the synthesis route of a key intermediate (5,14)-eicosadiyne-1-tetrahydropyran and synthesized it.
1,7-heptadiol, the starting material, reacted with hydrobromic acid to produce 7-bromheptane-1-ol, which hydroxy was protected by 2,3-dihydropyran . Then, it coupled with the heptaalkyne. The coupling product was taken off the 2,3-dihydropyran at the extremity, and the alcohol we obtained was brominated with CBr4 and PPh3, furnishing a new bromide (a). Next, the hydroxy of 5-hexyne-1-ol was protected by 2,3-dihydropyran with the catalytic reaction of PPTs. Alkylation of the protected alkyne, using bromide (a), produced the bis-acetylene. The total yield was 14.5%.
Some innovations we did as following: firstly, we designed a new synthesis route of (5,14)-eicosadiyne-1-tetrahydropyran; secondly, we studied the bromination reaction influence factors of 1,7-heptadiol in detail, including reaction time、reaction temperature、solvent dosage、reagent mole ratio; thirdly, we discussed the mechanism of 1-alkyne coupled with mono-bromide, and optimized the reaction condition.
We utilized silica gel column chromatography to separate and purify product, and applied infrared spectrum、1H NMR and mass spectrum to testify product structure. The final result indicated that our synthesis route was feasible.
引文
[1]吴升华,许福熙.花生四烯酸非环氧合酶产物与肾脏疾病[J].国外医学:泌尿系统手册,1994,14(5):208~211
[2] Proctor KG, Falck JR, Capdevila J. Intestinal vasodilation by epoxyeicosatrienoic acids: arachidonic acid metabolites metabolites produced by a cytochrome P450 monooxygenase[J]. Circ Res, 1987, 60(1):55~59
[3] Nelson DR, Koymans L, Kamataki T, et al. P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics, 1996, 6(1):1~42
[4] Kroetz DL, Zeldin DC. Cytochrome P450 pathways of arachidonic acid metabolism. Curr Opin Lipidol, 2002, 13(3):273-83
[5] Zeldin DC. Epoxygenase pathways of arachidonic acid metabolism. J Biol Chem, 2001, 276(39):36059~62
[6] Oltman CL, Weintraub NL, VanRollins M, et al. Epoxyeicosatrienoic acids and dihyodroxyeicosatrienoic acids are potent vasodilators in the canine coronary microcirculation. Circ Res, 1998, 83(9):932~9
[7] Chen G, Suzuki H, Weston AH. Acetylcholine releases endothelium-derived hyperpolarizing factor and EDRF from rat blood vessels[J]. Br J Pharmacol, 1988, 95: 1165～1174
[8] Rosolowsky M, Campbell WB. Role of PGI2 and epoxyeicosatrienoic acids in relaxation of bovine coronary arteriesto arachidonic acid[J]. Am J Physiol, 1993; 264:H327～H335
[9] Fukao M, Hattori Y, Kanno M, et al. Evidence against a role of cytochrome P450-derived arachidonic acid metabolites in endothelium-depentent hyperpolarization by acetylcholine in rat isolated mesenteric artery[J]. Br JPharmacol, 1997, 120:439～446
[10] Campbell WB, Gebremedhin D, Pratt PF, et al. Identification of epoxyeicosatrienoic acids as endothelium–derived hyperpolarizing factor[J]. Circ Res, 1996, 78:415～423
[11] Hecker M, Bara AT, Bauersachs J, et al. Characterization of endothelium- derived hyperpolarizing factor as a cytochrome P450-derived arachidonic acid metabolite in mammals[J]. J Physiol, 1994, 481(2):407～414
[12] Hu S, Kim H. Activation of K+ channel in vascular smooth muscles by cytochrome P450 metabolites of arachidonic acid[J]. Eur J Pharmacol, 1993, 230:215～221
[13] Fulton D, Mcgiff JC, Quilley J. Pharmacological evaluation of an epoxide as the hyperpolarizing factor mediating the nitric oxide independent vasodilator effect of bradykinin in the rat heart[J]. J Pharmacol Exp Ther, 1998, 287: 497～503
[14] Oltman CL, Weintraub NL, VanRollins M, et al. Epoxyeicosatrienoic acids and dihydroxyeicosatrienoic acids are potent vasodilators in the canine coronary microcirculation[J]. Circ Res, 1998, 83:932～939
[15] Hayabuohi Y, Nakaya Y, Matsuoka S, et al. Endothelium-derived hyperpolarizing factor activates Ca2+ activated K+ channle in porcine coronary artery smooth muscle cells[J]. J Cardiovasc Pharmacol, 1998, 32:642～649
[16] Imig JD, Insoho EW, Deivhmann PC, et al. Afferent arteriolar vasodilation to the sulfonimide analog of 11,12-epoxyeicosatrienoic acid involves protein kinase A[J]. Hypertension, 1999, 33 :408～413
[17] Medhora M, Harder D. Function role of epoxyeicosatrienoic acids and their production in astrocytes: approaches for gene transfer and therapy[J]. Int J Mol Med, 1998, 2:661～669
[18] Hoebel BG, Steyrer E, Graier WF. Origin and function of epoxyeicosatrienoic acids in vascular endothelial cells: more than just endothelium-derived hyperpolarizing factor [J]. Clin Exp Pharmacol Physiol, 1998, 25:826～830
[19] Nishikawa , Stepp DW, Chilian WM. Nitric oxide exerts feedback inhibition onEDHF-induced coronary arteriolar dilation in vivo. Am J Physiol Heart Circ Physiol, 2000, 279(2):H459~65
[20] Huang A, Sun D, Smith CJ, et al. In eNOS knockout mice skeletal muscle arteriolar dilation to acetylcholine is mediated by EDHF. Am J Physiol Heart Circ Physioi, 2000, 278(3):H762~8
[21] Chen J, Capdevila JH, Zeldin DC, et al. Inhibition of cardiac L-type calcium channels by epoxyeicosatrienoic acids. Mol Pharmacol, 1999, 55(2):288~295
[22] Node K, Huo Y, Ruan X, et al. Anti-inflammatory properties of cytochrome P450 epoxygenase-derived eicosanoids. Science, 1999, 285(5431):1276~9
[23] Node K, Ruan XL, Dai J, Yang SX, et al. Activation of Galpha’s mediates induction of tissue-type plasminogen activator gene transcription by epoxyeicosatrienoic acids. J Biol Chem, 2001, 276(19):15983~9
[24] Chen JK, Falck JR, Reddy KM, et al. Epoxyeicosatrienoic acids and their sulfonimide derivatives stimulate tyrosine phosphorylation and induce mitogenesis in renal epithelial cells. J Biol Chem, 1998, 273(44):29254~61
[25] Wu S, Chen W, Murphy E, et al. Molecular cloning, expression, and functional significance of a cytochrome P450 highly expressed in rat heart myocytes. J Biol Chem, 1997, 1-272(19):12551~9
[26] Zhang C, Harder DR. Cerebral capillary endothelial cell mitogenesis and morphogenesis induced by astrocytic epoxyeicosatrienoic Acid. 2002, 33(12):2957
[27] Fleming L, Fisslthaler B, Michaelis UR, et al. The coronary endothelium-derived hyperpolarizing factor (EDHF) stimulates multiple signaling pathways and proliferation in vascular cells. Pfiugers Arch, 2001, 442(4):511~8
[28] J. R. Falck, U. Murali Krishina, Y. Krishina Reddy, et al. Comparision of vasodilatory properties of 14,15-EET analogs: structural requirements for dilation[J]. AJP-Heart, 2003, 284:337~349
[29] Gauthier KM, Deeter C, Krishna UM, et al. 14,15-Epoxyeicosa-5(Z)-enoic acid: aselective epoxy eicosatrienoic acid antagonist that inhibits endothelium-dependent hyperpolarization and relaxation in coronary arteries[J]. Circ Res. 2002, 90(9):1028~36
[30] Louise S. Harrington, John R. Falck, Jane A. Mitchell. Not so EEZE: the‘EDHF’antagonist 14,15-epoxyeicosa-5(Z)-enoic acid has vasodilator properties in mesenteric arteries[J]. European Jounal of Pharmacology, 2004, 506:165~168
[31] Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med, 1971, 285(21): 1182~1186
[32] Hlatky L, Hahnfeldt P, Folkman J. Clinical application of antiangiogenic therapy: microvessel density, what it does and doesn’t tell us. J Natl Cancer Inst, 2002, 94(12): 883~893
[33] R.Kalluri. Discovery of Type IV Collagen Non-collagenous Damain as Novel Integrin Ligands and Endogenous Inhibitors of Angiogenesis. Cold Spring Harb Symp Quant Biol, 2002, 67: 255~266
[34] Nyberg P, Xie L, Kalluri R. Endogenous Inhibitors of Angiogenesis. Cancer Res, 2005, 65(10): 3967~3979
[35] Aeshima Y, Colorado PC, Torre A, et al. Distinct antitumor properties of a type IV collagen domain derived from basement membrane[J]. J Biol Chem, 2000, 275(28): 21340~21348
[36] Quade P, KnIght LC. Radiopharmaceuticals for targeting the angiogenesis marker alpha(v)beta(3). Q J Nucl Med, 2003, 47(3): 209~220
[37] Edchenko V, Zent R, Hudson BG. Alpha(v)beta3 and alpha(v)beta5 integrins bind both the proximal RGD site and non-RGD motifs within noncollagenous (NC1) domain of the alpha3 chain of type IV collagen: implication for the mechanism of endothelia cell adhesion. J Biol Chem, 2004, 279(4): 2772~2780
[38] Amamoto Y, Maeshima Y, Kitayama H, et al. Antiangiogenic endostatin peptide ameliorates renal alterations in the early stage of a type 1 diabetic nephropathy model.Diabetes, 2005, 54(10): 2891~2903
[39]巨勇,赵国辉,席婵娟.有机合成化学与路线设计[M] .第一版.北京:清华大学出版社,2002
[40]闻韧.药物合成反应[M].第一版.北京:化学工业出版社,1988
[41]伍越寰,李伟昶,沈晓明.有机化学[M].第一版.合肥:中国科技大学出版社,2002
[42]唐除痴,刘天麟.有机合成中的有机磷试剂[M].第一版.南京:南开大学出版社,1992
[43] Begue J P et al. Tetrahedron Lett. 1994, 35: 2907
[44] Hung Z Z, Huang X, Huang Y Z. Tetrahedron Lett. 1995, 36: 425
[45] Vodejs E, Cabaj J, Peterson M J. J. Org. Chem. 1993, 58:6509
[46] Jeganathan S, Tsukamoto M, Schlosser M. Synthesis 1990, 109
[47] Vodejs E, Peterson M J. J. Org. Chem. 1993, 58:1985
[48] Turos E, Boy K, Ren X F. J. Org. Chem. 1992, 57:6667
[49] Jeffery T, Gueugnot S, Listrmelle G. Tetrahedron Lett. 1992, 33:5757
[50] Dussault P, Lee I Q. J. Org. Chem. 1992, 57: 1952
[51] Lindlar H, Dubuis R. Org. Syn. Coll. Vol.5.1973, 880
[52] Kiri A D, Nadkarni D V, Fry J L. Tetrahedron Lett. 1994,35:1507
[53] Crousse B, Alami M, Linstrumelle G. Tetrahedron Lett. 1995, 36:4245
[54] Paley R S, Lafontaine J A, Ventura M P. Tetrahedron Lett. 1993,34:3663
[55] Bhatt R K et al. J. Amer. Chem. Soc. 1994,116:5050
[56] Normant J F. Bull. Soc. Chim. France. 1965, 859
[57] Campbell K N, Campbell B K. Org. Synth. Coll. Vol.4.1963, 117
[58] Lagowski J J.Ed.Macmillan Encyclopedia of Chemistry.Vol.1.New York: Simon & Schuster Macmillan, 1997, 80
[59] Buck M, Chong J M. Tetrahedron Lett. 2001,42:5825
[60] Rao A V R, Rdeey E R. Tetrahedron Lett.. 1986, 227: 2279
[61] Bechmann W et al. Synthesis. 1974, 423
[62] D.D.佩林.实验室化学药品的提纯方法[M].第一版.时雨译.化学工业出版社,1987
[63]焦家俊,有机化学实验[M].上海交通大学出版社,2000
[64]藤有为,庭玉华,冯留贵,等.简法合成ω-溴代醇-1[J].有机化学,1988(3):275~277
[65]克莱夫A,亨里克著.昆虫信息素的合成[M].科学出版社,1979
[66] Yoshikoshi, A., et al. J. Org. Chem. 42, 3772(1977)
[67]赵之中,周谨编译,有机化学中的保护基团[M].第一版.北京:科学出版社,1986
[68]范如霖.有机合成特殊技术[M].上海交通大学出版社,1987
[69] Snyder E I. J. Org. Chem. 1972, 37:1466
[70] Schaefer J P, Higgins J G. Org. Syn. Coll. Vol. 1973, 5: 249
[71] Schaefer J P, et al. ibid. Coll. Vol.1973, 5:142
[72] Brown H C, Bhat K S. Enantiomeric (Z)-and-(E)-crotyldiisopinocampheyl- boranes, synthesis in high optical of all four possible stereoisomers ofβ-methyhomoallhl alcohols[J]. J. Am. Chem. Soc., 1986, 108: 293~294
[73]李在国.有机中间体制备[M].第二版.北京:化学工业出版社,2001,274
[74]黄宪,王谚广,陈振初.新编有机合成反应[M].北京:化学工业出版社,2003
[2] Proctor KG, Falck JR, Capdevila J. Intestinal vasodilation by epoxyeicosatrienoic acids: arachidonic acid metabolites metabolites produced by a cytochrome P450 monooxygenase[J]. Circ Res, 1987, 60(1):55~59
[3] Nelson DR, Koymans L, Kamataki T, et al. P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics, 1996, 6(1):1~42
[4] Kroetz DL, Zeldin DC. Cytochrome P450 pathways of arachidonic acid metabolism. Curr Opin Lipidol, 2002, 13(3):273-83
[5] Zeldin DC. Epoxygenase pathways of arachidonic acid metabolism. J Biol Chem, 2001, 276(39):36059~62
[6] Oltman CL, Weintraub NL, VanRollins M, et al. Epoxyeicosatrienoic acids and dihyodroxyeicosatrienoic acids are potent vasodilators in the canine coronary microcirculation. Circ Res, 1998, 83(9):932~9
[7] Chen G, Suzuki H, Weston AH. Acetylcholine releases endothelium-derived hyperpolarizing factor and EDRF from rat blood vessels[J]. Br J Pharmacol, 1988, 95: 1165～1174
[8] Rosolowsky M, Campbell WB. Role of PGI2 and epoxyeicosatrienoic acids in relaxation of bovine coronary arteriesto arachidonic acid[J]. Am J Physiol, 1993; 264:H327～H335
[9] Fukao M, Hattori Y, Kanno M, et al. Evidence against a role of cytochrome P450-derived arachidonic acid metabolites in endothelium-depentent hyperpolarization by acetylcholine in rat isolated mesenteric artery[J]. Br JPharmacol, 1997, 120:439～446
[10] Campbell WB, Gebremedhin D, Pratt PF, et al. Identification of epoxyeicosatrienoic acids as endothelium–derived hyperpolarizing factor[J]. Circ Res, 1996, 78:415～423
[11] Hecker M, Bara AT, Bauersachs J, et al. Characterization of endothelium- derived hyperpolarizing factor as a cytochrome P450-derived arachidonic acid metabolite in mammals[J]. J Physiol, 1994, 481(2):407～414
[12] Hu S, Kim H. Activation of K+ channel in vascular smooth muscles by cytochrome P450 metabolites of arachidonic acid[J]. Eur J Pharmacol, 1993, 230:215～221
[13] Fulton D, Mcgiff JC, Quilley J. Pharmacological evaluation of an epoxide as the hyperpolarizing factor mediating the nitric oxide independent vasodilator effect of bradykinin in the rat heart[J]. J Pharmacol Exp Ther, 1998, 287: 497～503
[14] Oltman CL, Weintraub NL, VanRollins M, et al. Epoxyeicosatrienoic acids and dihydroxyeicosatrienoic acids are potent vasodilators in the canine coronary microcirculation[J]. Circ Res, 1998, 83:932～939
[15] Hayabuohi Y, Nakaya Y, Matsuoka S, et al. Endothelium-derived hyperpolarizing factor activates Ca2+ activated K+ channle in porcine coronary artery smooth muscle cells[J]. J Cardiovasc Pharmacol, 1998, 32:642～649
[16] Imig JD, Insoho EW, Deivhmann PC, et al. Afferent arteriolar vasodilation to the sulfonimide analog of 11,12-epoxyeicosatrienoic acid involves protein kinase A[J]. Hypertension, 1999, 33 :408～413
[17] Medhora M, Harder D. Function role of epoxyeicosatrienoic acids and their production in astrocytes: approaches for gene transfer and therapy[J]. Int J Mol Med, 1998, 2:661～669
[18] Hoebel BG, Steyrer E, Graier WF. Origin and function of epoxyeicosatrienoic acids in vascular endothelial cells: more than just endothelium-derived hyperpolarizing factor [J]. Clin Exp Pharmacol Physiol, 1998, 25:826～830
[19] Nishikawa , Stepp DW, Chilian WM. Nitric oxide exerts feedback inhibition onEDHF-induced coronary arteriolar dilation in vivo. Am J Physiol Heart Circ Physiol, 2000, 279(2):H459~65
[20] Huang A, Sun D, Smith CJ, et al. In eNOS knockout mice skeletal muscle arteriolar dilation to acetylcholine is mediated by EDHF. Am J Physiol Heart Circ Physioi, 2000, 278(3):H762~8
[21] Chen J, Capdevila JH, Zeldin DC, et al. Inhibition of cardiac L-type calcium channels by epoxyeicosatrienoic acids. Mol Pharmacol, 1999, 55(2):288~295
[22] Node K, Huo Y, Ruan X, et al. Anti-inflammatory properties of cytochrome P450 epoxygenase-derived eicosanoids. Science, 1999, 285(5431):1276~9
[23] Node K, Ruan XL, Dai J, Yang SX, et al. Activation of Galpha’s mediates induction of tissue-type plasminogen activator gene transcription by epoxyeicosatrienoic acids. J Biol Chem, 2001, 276(19):15983~9
[24] Chen JK, Falck JR, Reddy KM, et al. Epoxyeicosatrienoic acids and their sulfonimide derivatives stimulate tyrosine phosphorylation and induce mitogenesis in renal epithelial cells. J Biol Chem, 1998, 273(44):29254~61
[25] Wu S, Chen W, Murphy E, et al. Molecular cloning, expression, and functional significance of a cytochrome P450 highly expressed in rat heart myocytes. J Biol Chem, 1997, 1-272(19):12551~9
[26] Zhang C, Harder DR. Cerebral capillary endothelial cell mitogenesis and morphogenesis induced by astrocytic epoxyeicosatrienoic Acid. 2002, 33(12):2957
[27] Fleming L, Fisslthaler B, Michaelis UR, et al. The coronary endothelium-derived hyperpolarizing factor (EDHF) stimulates multiple signaling pathways and proliferation in vascular cells. Pfiugers Arch, 2001, 442(4):511~8
[28] J. R. Falck, U. Murali Krishina, Y. Krishina Reddy, et al. Comparision of vasodilatory properties of 14,15-EET analogs: structural requirements for dilation[J]. AJP-Heart, 2003, 284:337~349
[29] Gauthier KM, Deeter C, Krishna UM, et al. 14,15-Epoxyeicosa-5(Z)-enoic acid: aselective epoxy eicosatrienoic acid antagonist that inhibits endothelium-dependent hyperpolarization and relaxation in coronary arteries[J]. Circ Res. 2002, 90(9):1028~36
[30] Louise S. Harrington, John R. Falck, Jane A. Mitchell. Not so EEZE: the‘EDHF’antagonist 14,15-epoxyeicosa-5(Z)-enoic acid has vasodilator properties in mesenteric arteries[J]. European Jounal of Pharmacology, 2004, 506:165~168
[31] Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med, 1971, 285(21): 1182~1186
[32] Hlatky L, Hahnfeldt P, Folkman J. Clinical application of antiangiogenic therapy: microvessel density, what it does and doesn’t tell us. J Natl Cancer Inst, 2002, 94(12): 883~893
[33] R.Kalluri. Discovery of Type IV Collagen Non-collagenous Damain as Novel Integrin Ligands and Endogenous Inhibitors of Angiogenesis. Cold Spring Harb Symp Quant Biol, 2002, 67: 255~266
[34] Nyberg P, Xie L, Kalluri R. Endogenous Inhibitors of Angiogenesis. Cancer Res, 2005, 65(10): 3967~3979
[35] Aeshima Y, Colorado PC, Torre A, et al. Distinct antitumor properties of a type IV collagen domain derived from basement membrane[J]. J Biol Chem, 2000, 275(28): 21340~21348
[36] Quade P, KnIght LC. Radiopharmaceuticals for targeting the angiogenesis marker alpha(v)beta(3). Q J Nucl Med, 2003, 47(3): 209~220
[37] Edchenko V, Zent R, Hudson BG. Alpha(v)beta3 and alpha(v)beta5 integrins bind both the proximal RGD site and non-RGD motifs within noncollagenous (NC1) domain of the alpha3 chain of type IV collagen: implication for the mechanism of endothelia cell adhesion. J Biol Chem, 2004, 279(4): 2772~2780
[38] Amamoto Y, Maeshima Y, Kitayama H, et al. Antiangiogenic endostatin peptide ameliorates renal alterations in the early stage of a type 1 diabetic nephropathy model.Diabetes, 2005, 54(10): 2891~2903
[39]巨勇,赵国辉,席婵娟.有机合成化学与路线设计[M] .第一版.北京:清华大学出版社,2002
[40]闻韧.药物合成反应[M].第一版.北京:化学工业出版社,1988
[41]伍越寰,李伟昶,沈晓明.有机化学[M].第一版.合肥:中国科技大学出版社,2002
[42]唐除痴,刘天麟.有机合成中的有机磷试剂[M].第一版.南京:南开大学出版社,1992
[43] Begue J P et al. Tetrahedron Lett. 1994, 35: 2907
[44] Hung Z Z, Huang X, Huang Y Z. Tetrahedron Lett. 1995, 36: 425
[45] Vodejs E, Cabaj J, Peterson M J. J. Org. Chem. 1993, 58:6509
[46] Jeganathan S, Tsukamoto M, Schlosser M. Synthesis 1990, 109
[47] Vodejs E, Peterson M J. J. Org. Chem. 1993, 58:1985
[48] Turos E, Boy K, Ren X F. J. Org. Chem. 1992, 57:6667
[49] Jeffery T, Gueugnot S, Listrmelle G. Tetrahedron Lett. 1992, 33:5757
[50] Dussault P, Lee I Q. J. Org. Chem. 1992, 57: 1952
[51] Lindlar H, Dubuis R. Org. Syn. Coll. Vol.5.1973, 880
[52] Kiri A D, Nadkarni D V, Fry J L. Tetrahedron Lett. 1994,35:1507
[53] Crousse B, Alami M, Linstrumelle G. Tetrahedron Lett. 1995, 36:4245
[54] Paley R S, Lafontaine J A, Ventura M P. Tetrahedron Lett. 1993,34:3663
[55] Bhatt R K et al. J. Amer. Chem. Soc. 1994,116:5050
[56] Normant J F. Bull. Soc. Chim. France. 1965, 859
[57] Campbell K N, Campbell B K. Org. Synth. Coll. Vol.4.1963, 117
[58] Lagowski J J.Ed.Macmillan Encyclopedia of Chemistry.Vol.1.New York: Simon & Schuster Macmillan, 1997, 80
[59] Buck M, Chong J M. Tetrahedron Lett. 2001,42:5825
[60] Rao A V R, Rdeey E R. Tetrahedron Lett.. 1986, 227: 2279
[61] Bechmann W et al. Synthesis. 1974, 423
[62] D.D.佩林.实验室化学药品的提纯方法[M].第一版.时雨译.化学工业出版社,1987
[63]焦家俊,有机化学实验[M].上海交通大学出版社,2000
[64]藤有为,庭玉华,冯留贵,等.简法合成ω-溴代醇-1[J].有机化学,1988(3):275~277
[65]克莱夫A,亨里克著.昆虫信息素的合成[M].科学出版社,1979
[66] Yoshikoshi, A., et al. J. Org. Chem. 42, 3772(1977)
[67]赵之中,周谨编译,有机化学中的保护基团[M].第一版.北京:科学出版社,1986
[68]范如霖.有机合成特殊技术[M].上海交通大学出版社,1987
[69] Snyder E I. J. Org. Chem. 1972, 37:1466
[70] Schaefer J P, Higgins J G. Org. Syn. Coll. Vol. 1973, 5: 249
[71] Schaefer J P, et al. ibid. Coll. Vol.1973, 5:142
[72] Brown H C, Bhat K S. Enantiomeric (Z)-and-(E)-crotyldiisopinocampheyl- boranes, synthesis in high optical of all four possible stereoisomers ofβ-methyhomoallhl alcohols[J]. J. Am. Chem. Soc., 1986, 108: 293~294
[73]李在国.有机中间体制备[M].第二版.北京:化学工业出版社,2001,274
[74]黄宪,王谚广,陈振初.新编有机合成反应[M].北京:化学工业出版社,2003