脱落酸的全合成及其2，3-环丙化类似物的合成研究
|
摘要
ABA是一种广泛存在于植物体内的抑制性植物激素，与植物离层形成、诱导休眠、抑制发芽、促进器官衰老和脱落、增强抗逆性等密切相关。本论文设计并完成了一条全新的外消旋脱落酸(1)全合成路线，从廉价的工业原料氧化异佛尔酮和丁炔醇出发，经过缩酮化反应、氧化反应、Wittig-Horner反应、CrSO_4选择性还原反应以及水解等七步反应实现了脱落酸的全合成，总产率达13％，与以往路线相比，该路线所用试剂廉价、合成路线简单，但产率有待提高。
为解决脱落酸2位双键在环境中易光异构化为反式结构的问题，依据电子等排体原理，将2,3-位的烯丙型的结构改变为环丙型结构，将可能解决光异构化的问题。为此，我们通过环丙烷化、亲核加成及三键选择性还原等一系列反应成功合成了ABA的2,3-环丙化类似物(88)。
所合成目标化合物及15个未见文献报道的中间体都经过了~1H和~(13)CNMR、GC／MS及红外谱图的验证
Abscisic acid is one of the natural plant hormone extensively distributed in higher plants and regulates many processes in plants such as the acceleration of abscission, induction of dormancy, inhibition of rooting, and stimulation of stomatal closure. In this thesis, we describe a facile and economical synthesis of (?-abscisic acid(l) from keto-isophorone and 3-butyn-2-ol through ketalization, oxidization, Witting-Horner reaction, reduction with chromium( II) sulfate and other steps in 13% total yields. Compared to the previous routes, the starting materials are more commercially available and cheaper and the synthetic process is more easily controlled in our method, but the yield of this route is still to be improved.
As to isostere principle, cyclopropyl and methyl vinyl are a couple of isostere. Cis-C=C configuration on 2 position is easily isomerized to trans-form in environment according to literatures, but cycloproyl do it difficut relatively. So, replacement of 2,3- allyl unit by cyclopropyl group might give a practical method to get over the problem. For the interest of this opinion, we designed and synthesized compound (88) successfully through reactions such as cyclopropanation, nucleophilic addictions and selective reduction of triple bond etc.
The structures of the target compounds and 15 intermediates have been confirmed by 1H NMR, 13C NMR, GC/MS and IR.
为解决脱落酸2位双键在环境中易光异构化为反式结构的问题，依据电子等排体原理，将2,3-位的烯丙型的结构改变为环丙型结构，将可能解决光异构化的问题。为此，我们通过环丙烷化、亲核加成及三键选择性还原等一系列反应成功合成了ABA的2,3-环丙化类似物(88)。
所合成目标化合物及15个未见文献报道的中间体都经过了~1H和~(13)CNMR、GC／MS及红外谱图的验证
Abscisic acid is one of the natural plant hormone extensively distributed in higher plants and regulates many processes in plants such as the acceleration of abscission, induction of dormancy, inhibition of rooting, and stimulation of stomatal closure. In this thesis, we describe a facile and economical synthesis of (?-abscisic acid(l) from keto-isophorone and 3-butyn-2-ol through ketalization, oxidization, Witting-Horner reaction, reduction with chromium( II) sulfate and other steps in 13% total yields. Compared to the previous routes, the starting materials are more commercially available and cheaper and the synthetic process is more easily controlled in our method, but the yield of this route is still to be improved.
As to isostere principle, cyclopropyl and methyl vinyl are a couple of isostere. Cis-C=C configuration on 2 position is easily isomerized to trans-form in environment according to literatures, but cycloproyl do it difficut relatively. So, replacement of 2,3- allyl unit by cyclopropyl group might give a practical method to get over the problem. For the interest of this opinion, we designed and synthesized compound (88) successfully through reactions such as cyclopropanation, nucleophilic addictions and selective reduction of triple bond etc.
The structures of the target compounds and 15 intermediates have been confirmed by 1H NMR, 13C NMR, GC/MS and IR.
引文
[1] K Ohkuma, F T Addicott, J L Lyon et al. Abscisic accelerating substance from young cotton fruit. Science 1963, 142: 1593
[2] Addicott F T, Carns H R, "History and introduction In Abscisic Acid", F T Addicot(ed.), Praeger Publisher, New York, 1983, 331～363
[3] Y. Li; C. Walton, Xanthophylls and abscisic acid biosynthesis in water-stressed bean leaves. Plant Physiol., 1987,85,910-915
[4] D. M. Paton, A. K. Dhawan, R. R. Willing, Effect of Eucalyptus growth regulators on water loss from plant leaves. Plant Physiol., 1980, 66, 254-256
[5] L. V. Gusta, J. B. O'Connor, M. J. T. Reaney, The effect of growth regulators on the winter survival of winter wheat. Plant Growth Subst. 1988,13, 531-536
[6] L. V. Gusta, J. B. O'Connor, G. P. Lafond, The effect of fungicides and plant growth regulators applied as a seed treatment on freezing tolerance of winter wheat. Can. J. Plant Sci. 1994,74(1), 63-69
[7] T. H. H. Chen, P. H. Li, M. Brenner, Involvement of abscisic acid in potato cold acclimation. Plant Physiol., 1983, 71, 362
[8] J.A.D.Zeevaart, R.A.Creelman, Metabolism and physiology of ABA. Ann. Rev. Plant Physiol. Plant Mol. Biol., 1998, 39, 439-473
[9] B.V.Milborrow, "History and introduction In Abscisic Acid", F T Addicot(ed.),praeger, New York, 1983, 79-111
[10] B.V.Mliborrow, The metabolism of abscisic acid. Journal of Experimental Botany, 1970,21,17-29
[11] W.V.Dashek, B.N.Singh, D.C.Walton, Abscisic acid localization and metabolism in bareley aleurone layers. Plant Physiol., 1979, 64, 43-48
[12] D.C.Walton, E.Sondheimer, Metabolism of 2-~(13)C-(±)-abscsic acid in excised bean axes. Plant Physiol., 1972,49,285-289
[13] J W Cornforth, ,B V Milborrow, G Ryback. Synthesis of(±)-abscisic Ⅱ. Nature, 1965,206,715
[14] D L Roberts, R A.Heckman, B P Hege et al. Synthesis of(RS)-Abscisic Acid. J. Org. Chem. 1968, 33(9): 3566～3569
[15] B T Kim, Y K Min, T Asomi. Synthesis of 2-fluoroabscisic acid: A potential phto-stable abscisic acid. Tetrahedron Lett. 1997, 38(10): 1797～1800
[16] T Asami, K Sekimata, J M Wang, Preparation of(±)-[1, 2-~(13)C_2]Abscisic Acid for Use as a Stable and Pure Internal Standard. J Chem-Research(s)1999: 658～659
[17] S Takahashi, T Oritani, K Yamashita. Total synthesis of (±)-Methyl Phaseates. Agric. Biol. Chem.1986, 50: 1589～1595
[18] Y Todoroki, N Hariai, K Koshimizu. 8'-and 9'-methoxyabscisic acid as antimetabolic analogs of
abscisic acid. Biosci. Biotech. Biochem. 1994, 58: 707～715
[19] Y Todoroki, N Hariai, K Koshimizu. 8',8'-Difluoro-and 8',8',8'-Trifluoroabscisic acids as highly potent, long-lasting analogues of abscisic acid. Phytochemistry 1995,38(3): 561～568
[20] S Nakano, Y Todoroki, N Hariai et al. Synthesis and biological activity of 7'-, 8'-, and 9'-alkyl analogues of abscisic acid. Biosci. Biotech. Biochem. 1995, 59: 1699～1706
[21] H J. Mayer, N Rigassi, U Schwietter et al. Synthesis of Abscisic Acid, Helv. Chim. Acta. 1976,59: 1424～1427
[22] P A Rose, S R Abrams, A C Show. Synthesis of Chral Acetylenic Analoge of The Plant Hormone Abscisic Acid. Tetrahedron: Asymmetry 1992, 3(3): 443～450
[23] P A Rose, B Lei, A C Show, Probing the role of the hydroxyl group of ABA: Analogues with a methyl ether at C-1'. Phytochemistry 1996,41(5): 1251～1258
[24] M G Constantino, P M Donate, N Petragnani. An Efficient Synthesis of(±)-Abscisic Acid. J. Org. Chem. 1986. 51: 253～254
[25] N Lamb, A C Shaw, S R Abrams. Oxidation of the 8'-position of a biologically active abscisic acid analogue. Phytochemistry 1993,34(4): 905～917
[26] S Takahashi, T Oritani, K Yamashita. Total synthesis of(+)-Methyl Phaseate from(-)-β-pinene. Agric. Biol. Chem. 1988, 52: 1633～1635
[27] S Takahashi, T Oritani, K Yamashita. Total synthesis of(+)-Methyl trisporate B, fungal sex hormone. Tetrahedron 1988,44(23): 7081-7088
[28] S Takahashi, T Oritani, K Yamashita. Synthesis of(+)-Methyl Phaseate and its isomer from(-)-β-pinene. Agric. Biol. Chem. 1989, 53: 2711～2718)
[29] T W Balko, S C Fields, J D Webster. Total synthesis of(±)-8'-trifluoromethyl abscsic acid Tetrahedron Lett. 1999, 40: 6347～6351
[30] K Sakai, K Takahashi, T Nkano. Convenient Syntheses of Optically Active Abscsic Acid and Xanthoxin. Tetrahedron 1992, 48(3): 8229～8238
[31] M Acemoglu, P Uebelhart, M Rey et al. Syntheses of enantionericaily pure violaxanthins and related compounds. Helv. Chim. Acta. 1988, 71: 931～957
[32] M G Constantino, P Losco, A Novel Synthesis of(±)-Abscisic Acid. J. Org. Chem. 1989,54: 681～683
[33] B Lei, S R Abrams, B Ewan et al. Achiral Cyclohexadienone Analogues of Abscisic Acid: Synthesis and Biological Activity. Phytochemistry 1994,37(2):289-296
[34] Y Todoroki, S Nakano, N Hariai et al. Synthesis ,biological activity and metabolism of 8',8', 8'-trideutero abscisic acid. Biosci. Biotech. Biochem. 1997, 61(11): 1872～1876
[35] T Inoue, T Oritani. Synthesis of(±)-methyl 6'α-dimethyl-6'α-cyanoabscisate and(±)-methyl 6'α-dimethyl-6'α-methoxycarbonyl abscisate. Biosci. Biotech. Biochem. 2000, 64(5): 1071～1074
[36] J Cornforth, J E Hawes, R Mallaby, A Stereospecific Synthesis of(±)-Abscisic Acid. Aust. J. Chem. 1992, 45: 179～185
[37] P.A.Rose, S.R.Abrams, L.V.Gusta, Synthesis resolution and biological activity of 7',7'-difluoro
abscisic acid. Phytochemistry, 1992, 31(4), 1105-1110
[38] 平井，伸博；脱落酸衍生物．日本专利，JP95242590，1995
[39] 金范泰，闵容基，朴鲁均；新型氟代脱落酸衍生物及含此类化合物的植物生长调节剂．日本专利 JP95300443，1995
[40] B.T.Kim, Y.K.Min, T.Asami, Synthesis and biological activities of new fluorinated abscisic acid. Bioorg. Med. Chem. Lett., 1995,5,275
[41] S.Arai, Y.Todorki, S.Ibaraki, Synthesis and biological activity of 3'-chloro, -bromo, and -iodoa bscisic acids, and biological activity of 3'-fluoro-8'-hydroxy abscisic acid. Phytochemistry, 1999, 52,1185-1193
[42] Y.Todorki, N.Hirai, H.Ohigashi, Synthesis, biological activity and metabolism of S-(+)-fluoroa bscisic acid. Tetrahedron. 1995,51(25),6911-6926
[43] Y.Todorki, N.Hirai, K.Koshimizu, Synthesis and biological activity of 1'-deoxy-1'-fluoro- and 8'-fluoroabscisic acid. Phytochemistry, 1995,40(3),633-641
[44] Y.Todoroki, S.Nakano, N.Hirai, Synthesis and biological activity of 8'-methylene and 8'-methylidyneabscisic acid. Biosci. Biotech. Biochem. 1997,61 (12),2043-2045
[45] S.R.Abrams, P.A.Rose, A.J.Culter, 8'-Methylene Abscisic acid. Plant Physiol., 1997,114,89-97
[46] M.Nanzyo,T.Oritani,K.Yamashita; Synthesis and physiological activity of monodemethyl abscisic acid and methyl 5-(1',6'-epoxy-2',2'-dimethyleyclohexyl)-methyl-(2Z,4E)-2,4-pentadienoate.. Agric.Biol. Chem.; 1977, 41(9), 1711-1720
[47] J.A.Wilmer, S.R.Abrams, J.P.F.G.Helsper, Role of the ring methyl groups in abscisic acid activity in erucici acid accumulation in oilseed rape. J. Plant Growth Regul., 1998,17,19-23
[48] N.Lamb, N.Wahab, P.A.Rose, Synthesis, biological activity and metabolism of a deuterated analogue of the plant hormone S-(+)-abscisic acid. Phytochemistry, 1996,41(1),23-28
[49] M.Perras, P.A.Rose, E.W.Pass; Defining steric, electronic and conformational requirements of carrier-mediated uptate of abscisic acid in barley suspension culture cells. Phytochemistry,1997,46(2),215-222
[50] 丸茂，晋吾，白井；脱落酸类似物与植物生长调节剂．日本专利，JP931001，1991
[51] J.L.Ward, M.H.Beale, Caged plant hormones. Phytochemistry, 1995,36(4), 811-816
[52] L.V.Gusta, The effect of abscisic acid and abscisic acid metabolites on the germination of cressseed. Can. J. Bot., 1992,70(8),1550-1555
[53] M.K.Walker-Simmons,P.A.Rose,A.C.Shaw; The 7'-methyl group of abscisic acid is critical for biological activity in wheat embryo germination. Plant Physiol.; 1994,106,1279-1284
[54] B.T.Miborrow; he effects of synthetic dl-dormin (abscisin Ⅱ) on the growth of oat mesocotyl. Planta; 1966,70,155-158
[55] K.Yamashita, T.Watanabe, M.Watanabe, Studies on abscisic acid. Part ⅩⅥ. Synthesis and biological activity of methyl 3-demethylabscisate and its related analogs. Agric. Biol. Chem.,1982, 46(12), 3069-3073
[56] T. Asami, Y. K.Min, T. Nokano, Synthesis and biological activity of 4'-methoxy derivatives of
abscisic acid. Bioorg. Med. chem. Lett., 2000,10: 1571～1574
[57] S.Tamura, M.Nagao, Synthesis of novel plant growth inhibitors structurally related to abscisic acid. Agr Biol. Chem., 1969,33(2),296-298
[58] S.Tamura, M.Nagao, 5-(1,2-epoxy-2,6,6-trimethyl-1-cyclohex-yl)-3-methyl-cis,trans-2,4-pentadienoic acid and its esters: plant-growth inhibitors structurally related to abscisic acid. planta.,1969,85(2),209-212
[59] S.Tamura, M.Nagao, Synthesis and biological activity of 5-(1-Hydroxy-2,6,6-tri methyl-2-cyclohexen-1-yl)-3-methyl-cis,trans-2,4-pentadienoic ester and somother abscisic acid analogs. Agr. Biol. Chem., 1969, 33(9),1357-1360
[60] Y.Todoroki,S.Nakano,N.Hirai; Ring conformational requirement for biological activity of abscisic acid probed by the cyclopropane analogues. Tetrahedron 1996, 52(24), 8081-8098
[61] T.Oritani,K.Yamashita; Synthesis and biological activity of(±)-2',3'-dihydroabscsic acid. Agric. Biol. Chem.; 1982,46, 817-818
[62] H.Yamamoto,T.Oritani,K.Yamashita; Synthesis of chiral 3'-hydroxy-r-ionylideneacetic acid. Agric. Biol. Chem.; 1988,52,2203-2208
[63] T.J. Blake, E.Bevilacgua, G.A.Hunt, Effects of abscsic and its acetylenic alcohol on dormancy, root development and transpiration in three conifer species. Plant Physiol., 1990,80,371-378
[64] D.C.Walton, in "Abscisic Acid" ed. by F.T.Addicot, praeger, New York, 1983, 1-21
[65] 石德清，盛梓良，吴宏，陈茹玉；2001．O(O，O’-二乙基膦酰基芳基亚甲基)-5-取代苯基-2E,4E-戊二烯酸酯的合成与生物活性研究．35：296～300
[66] 龙姝，陈敏，莫文妍，石德清；2002．N-[甲氧(乙氧)羰基亚甲基]-5-取代苯基-2E，4E-戊二烯酰胺的合成与生物活性研究．36：185～203
[67] 石德清，陈茹玉：2002．含α-氨基膦酸酯的脱落酸类似物的合成与生物活性研究．19：780～783
[68] 吴清来，毛淑芬，覃兆海；脱落酸的全合成．《化学通报》(已录用)
[69] 吴清来，毛淑芬，覃兆海；脱落酸衍生物及类似物研究进展．《植物学通报》(已录用)
[70] 赵中伟，李洪桂，霍广生等；电子等排原理及利用其设计分离试剂的可行性．《中南工业大学学报》，2002，33(6)，584～587
[71] 刘长令：生物电子等排及其在新农药创制中的应用．《农药》，1998，37(2)，1～7
[72] C E Castro, R D Stephens; The Reduction of Multipe Bonds by Low-Valent Transition Metal Ions.The Homogeneous Reduction of Acetylenes by Chromous Sulfate. J.Am.Chem.Soc., 1964,86,4358-4363
[73] Yu G Gololobov, A N Nesmeyanov, V P Lysenko, I E Boldeskul; Twenty-five Years of Dimethylsufoxonium Methylide(Corey's Reagent). tetrahedron, 1987,43(12), 2609～2651
[74] An-Hu Li, Li-Xin Dai, Varinder K Aggarwal; Asymmetric Yielde Reactions: Epoxidation, Cyclopropanation, Aziridination, Olefination, and Rearrangement. Chem. Rev. 1997, 97(6), 2341～2372
[75] A.-H. Li, Y.-G. Zhou, L.-X. Dai, et.al. Asymmetric aziridination over ylidies: highly stereoselective synthesis of acetylenyl-N-sulfonylaziridines. Angew.Chem.,Int.Ed.Engl., 1997, 36(12),1317～1319
[76] W B Austin, N Bilow, W J Kelleghan, K S Y Lau; Fcaile Synthesis of Ethynylated Benzoic Acid Derivatives and Aromatic Compounds via Ethynytrimethylsilane. J. Org. Chem., 1981, 46
(11), 2280～2286;
[77] M Ahmed, G C Barley, M T W Hearn, E R H Jones, V Thaller, J A Yates; Natural Acetylenes. Part XLⅡ. Polyacetylenes from Cultures of the Fungus Fistulina pallida(Berk. And Rev.). J Chem. Soc. Perkin Ⅰ, 1974,1981～1984
[78] Chen Zhao-Gen, Zhou Da-Shun, Zhou Jing-Yao, Wu Shi-Hui; Selectivety of the Reaction for Substituted Propargyl Bromide with Aldehydes Promoted by Metal Tin. Acta Chemica Sinica, 1997,1138～1144;
[79] Michael B. Smith, in "Organic Synthesis" ed. by Kent A.Peterson, praeger, New York,2002, 670～675
[80] 李淑勉，侯守军，李占才等：2，6，6-三甲基-4，4-乙二氧基-2-环己烯-1-酮的合成研究，厦门大学学报(自然科学版)，1999，38，464
[81] 彭美静，俞善信；氯化铁催化合成氯乙酸乙酯，精细化工，1995，12(3)，56～58
[82] 慕长伟；4-[3-(吡啶-4-基)-3-取代苯基丙烯酰]吗啉类化合物的合成及杀菌活性的研究，硕士学位论文，2003，中国农业大学
[83] J R Hanson, E Premuzic; The reduction of organic compounds with chromium(Ⅱ) salts.Angew. Chem.,Int.Ed.Engl., 1968, 7(2), 247～320
[84] 吴清来，毛淑芬，覃兆海；氧化异佛尔酮1位羰基缩酮的选择性合成研究，《化学试剂》(已录用)
[85] 吴清来，毛淑芬，覃兆海；氧化异佛尔酮缩酮化产物的NMR特征，《波谱学杂志》(已录用)
[86] 吴清来，毛淑芬，覃兆海；3-[1-羟基-2，6，6-三甲基-4，4-(乙二氧基)-2-环己烯基]丙炔醇的合成及其稳定性研究，《化学试剂》(已录用)
[87] 郑可利，王贵杰，袁谷；α，β-炔醛异构化高立体选择性合成(2E，4E)-碳十四共轭烯醛．《高等化学学报》，2002，23，855～856
[88] Y Leblanc, B J Fitzimmons, J Adams, et.al. The total synthesis of 12-HETE (12-hydroxyeicosat etraenioc acid) and 12,20-diHETE. J. Org. Chem., 1986, 51(6),789～793
[89] J R Pfister, D V Krishna Murthy; Synthesis of three potential inhibitors of leukotriene biosynthesis. J. Med.Chem., 1983, 26(8), 1099～1103
[90] 邢其毅，徐瑞秋，周政等，《基础有机化学》，高等教育出版社，北京，1993，215～230
[91] 马淳安，《有机电化学合成导论》，科学出版社，北京，2002，205～211
[92] J R Hanson; Applications of chromium(Ⅱ) salts in preparative organic chemistry. Synthesis,1974，1～8
[93] 吴义杰，周明德，刘超美等；碘化三甲基氧化锍的制备．《中国医药工业杂志》，1998，29(3)，129～130
[94] 景肴壁，顾文鑫，任新峰；多取代环丙烷化合物的合成研究．《高等化学学报》，2001，22(10)，1691～1692
[95] 徐明华，林国强：手行金属催化剂在不对称环丙烷化反应中的应用进展．《有机化学》，2000，20(4)，475～485
[96] Yang Tang, Yao-Zeng Huang, Li-Xin Dai, et. al. Cyclopropanation reaction of allylic ylides with α,β-unsaturated esters and amides: tuning of stereoseletivity and the dramatic effect of lithium salts.
J. Org. Chem.. 1996, 61(17), 5762～5769
[97] 周文勇，叶启亮，齐鸣斋等；β-异佛尔酮催化氧化制酮代异佛尔酮，《化学世界》，2002，9，481～483
[98] 赵增国，张松威，耿奎士等，氧化异佛尔酮(3，5，5-三甲基环己烯-1，4-二酮)的合成研究1998，15(4)，42～45
[99] 胡艾希，赵海涛，范国枝等；离子交换树脂催化合成(2R，4R)-酒石酸二甲酯，《湖南大学学报》，1998，25(1)，23～26
[100] I Sakamoto, H Ohrui; Practical synthesis of the disaccharide epitope, D-Galactopyranosyl-α-1,3-D-galactopyranose, by using 1,2;5,6-Di-O-cyclohexylidene-α-D-alactopyranose as the Glycosyl acceptor. Biosci. Biotchnol. Biochem, 2000, 64(9), 1974～1977
[2] Addicott F T, Carns H R, "History and introduction In Abscisic Acid", F T Addicot(ed.), Praeger Publisher, New York, 1983, 331～363
[3] Y. Li; C. Walton, Xanthophylls and abscisic acid biosynthesis in water-stressed bean leaves. Plant Physiol., 1987,85,910-915
[4] D. M. Paton, A. K. Dhawan, R. R. Willing, Effect of Eucalyptus growth regulators on water loss from plant leaves. Plant Physiol., 1980, 66, 254-256
[5] L. V. Gusta, J. B. O'Connor, M. J. T. Reaney, The effect of growth regulators on the winter survival of winter wheat. Plant Growth Subst. 1988,13, 531-536
[6] L. V. Gusta, J. B. O'Connor, G. P. Lafond, The effect of fungicides and plant growth regulators applied as a seed treatment on freezing tolerance of winter wheat. Can. J. Plant Sci. 1994,74(1), 63-69
[7] T. H. H. Chen, P. H. Li, M. Brenner, Involvement of abscisic acid in potato cold acclimation. Plant Physiol., 1983, 71, 362
[8] J.A.D.Zeevaart, R.A.Creelman, Metabolism and physiology of ABA. Ann. Rev. Plant Physiol. Plant Mol. Biol., 1998, 39, 439-473
[9] B.V.Milborrow, "History and introduction In Abscisic Acid", F T Addicot(ed.),praeger, New York, 1983, 79-111
[10] B.V.Mliborrow, The metabolism of abscisic acid. Journal of Experimental Botany, 1970,21,17-29
[11] W.V.Dashek, B.N.Singh, D.C.Walton, Abscisic acid localization and metabolism in bareley aleurone layers. Plant Physiol., 1979, 64, 43-48
[12] D.C.Walton, E.Sondheimer, Metabolism of 2-~(13)C-(±)-abscsic acid in excised bean axes. Plant Physiol., 1972,49,285-289
[13] J W Cornforth, ,B V Milborrow, G Ryback. Synthesis of(±)-abscisic Ⅱ. Nature, 1965,206,715
[14] D L Roberts, R A.Heckman, B P Hege et al. Synthesis of(RS)-Abscisic Acid. J. Org. Chem. 1968, 33(9): 3566～3569
[15] B T Kim, Y K Min, T Asomi. Synthesis of 2-fluoroabscisic acid: A potential phto-stable abscisic acid. Tetrahedron Lett. 1997, 38(10): 1797～1800
[16] T Asami, K Sekimata, J M Wang, Preparation of(±)-[1, 2-~(13)C_2]Abscisic Acid for Use as a Stable and Pure Internal Standard. J Chem-Research(s)1999: 658～659
[17] S Takahashi, T Oritani, K Yamashita. Total synthesis of (±)-Methyl Phaseates. Agric. Biol. Chem.1986, 50: 1589～1595
[18] Y Todoroki, N Hariai, K Koshimizu. 8'-and 9'-methoxyabscisic acid as antimetabolic analogs of
abscisic acid. Biosci. Biotech. Biochem. 1994, 58: 707～715
[19] Y Todoroki, N Hariai, K Koshimizu. 8',8'-Difluoro-and 8',8',8'-Trifluoroabscisic acids as highly potent, long-lasting analogues of abscisic acid. Phytochemistry 1995,38(3): 561～568
[20] S Nakano, Y Todoroki, N Hariai et al. Synthesis and biological activity of 7'-, 8'-, and 9'-alkyl analogues of abscisic acid. Biosci. Biotech. Biochem. 1995, 59: 1699～1706
[21] H J. Mayer, N Rigassi, U Schwietter et al. Synthesis of Abscisic Acid, Helv. Chim. Acta. 1976,59: 1424～1427
[22] P A Rose, S R Abrams, A C Show. Synthesis of Chral Acetylenic Analoge of The Plant Hormone Abscisic Acid. Tetrahedron: Asymmetry 1992, 3(3): 443～450
[23] P A Rose, B Lei, A C Show, Probing the role of the hydroxyl group of ABA: Analogues with a methyl ether at C-1'. Phytochemistry 1996,41(5): 1251～1258
[24] M G Constantino, P M Donate, N Petragnani. An Efficient Synthesis of(±)-Abscisic Acid. J. Org. Chem. 1986. 51: 253～254
[25] N Lamb, A C Shaw, S R Abrams. Oxidation of the 8'-position of a biologically active abscisic acid analogue. Phytochemistry 1993,34(4): 905～917
[26] S Takahashi, T Oritani, K Yamashita. Total synthesis of(+)-Methyl Phaseate from(-)-β-pinene. Agric. Biol. Chem. 1988, 52: 1633～1635
[27] S Takahashi, T Oritani, K Yamashita. Total synthesis of(+)-Methyl trisporate B, fungal sex hormone. Tetrahedron 1988,44(23): 7081-7088
[28] S Takahashi, T Oritani, K Yamashita. Synthesis of(+)-Methyl Phaseate and its isomer from(-)-β-pinene. Agric. Biol. Chem. 1989, 53: 2711～2718)
[29] T W Balko, S C Fields, J D Webster. Total synthesis of(±)-8'-trifluoromethyl abscsic acid Tetrahedron Lett. 1999, 40: 6347～6351
[30] K Sakai, K Takahashi, T Nkano. Convenient Syntheses of Optically Active Abscsic Acid and Xanthoxin. Tetrahedron 1992, 48(3): 8229～8238
[31] M Acemoglu, P Uebelhart, M Rey et al. Syntheses of enantionericaily pure violaxanthins and related compounds. Helv. Chim. Acta. 1988, 71: 931～957
[32] M G Constantino, P Losco, A Novel Synthesis of(±)-Abscisic Acid. J. Org. Chem. 1989,54: 681～683
[33] B Lei, S R Abrams, B Ewan et al. Achiral Cyclohexadienone Analogues of Abscisic Acid: Synthesis and Biological Activity. Phytochemistry 1994,37(2):289-296
[34] Y Todoroki, S Nakano, N Hariai et al. Synthesis ,biological activity and metabolism of 8',8', 8'-trideutero abscisic acid. Biosci. Biotech. Biochem. 1997, 61(11): 1872～1876
[35] T Inoue, T Oritani. Synthesis of(±)-methyl 6'α-dimethyl-6'α-cyanoabscisate and(±)-methyl 6'α-dimethyl-6'α-methoxycarbonyl abscisate. Biosci. Biotech. Biochem. 2000, 64(5): 1071～1074
[36] J Cornforth, J E Hawes, R Mallaby, A Stereospecific Synthesis of(±)-Abscisic Acid. Aust. J. Chem. 1992, 45: 179～185
[37] P.A.Rose, S.R.Abrams, L.V.Gusta, Synthesis resolution and biological activity of 7',7'-difluoro
abscisic acid. Phytochemistry, 1992, 31(4), 1105-1110
[38] 平井，伸博；脱落酸衍生物．日本专利，JP95242590，1995
[39] 金范泰，闵容基，朴鲁均；新型氟代脱落酸衍生物及含此类化合物的植物生长调节剂．日本专利 JP95300443，1995
[40] B.T.Kim, Y.K.Min, T.Asami, Synthesis and biological activities of new fluorinated abscisic acid. Bioorg. Med. Chem. Lett., 1995,5,275
[41] S.Arai, Y.Todorki, S.Ibaraki, Synthesis and biological activity of 3'-chloro, -bromo, and -iodoa bscisic acids, and biological activity of 3'-fluoro-8'-hydroxy abscisic acid. Phytochemistry, 1999, 52,1185-1193
[42] Y.Todorki, N.Hirai, H.Ohigashi, Synthesis, biological activity and metabolism of S-(+)-fluoroa bscisic acid. Tetrahedron. 1995,51(25),6911-6926
[43] Y.Todorki, N.Hirai, K.Koshimizu, Synthesis and biological activity of 1'-deoxy-1'-fluoro- and 8'-fluoroabscisic acid. Phytochemistry, 1995,40(3),633-641
[44] Y.Todoroki, S.Nakano, N.Hirai, Synthesis and biological activity of 8'-methylene and 8'-methylidyneabscisic acid. Biosci. Biotech. Biochem. 1997,61 (12),2043-2045
[45] S.R.Abrams, P.A.Rose, A.J.Culter, 8'-Methylene Abscisic acid. Plant Physiol., 1997,114,89-97
[46] M.Nanzyo,T.Oritani,K.Yamashita; Synthesis and physiological activity of monodemethyl abscisic acid and methyl 5-(1',6'-epoxy-2',2'-dimethyleyclohexyl)-methyl-(2Z,4E)-2,4-pentadienoate.. Agric.Biol. Chem.; 1977, 41(9), 1711-1720
[47] J.A.Wilmer, S.R.Abrams, J.P.F.G.Helsper, Role of the ring methyl groups in abscisic acid activity in erucici acid accumulation in oilseed rape. J. Plant Growth Regul., 1998,17,19-23
[48] N.Lamb, N.Wahab, P.A.Rose, Synthesis, biological activity and metabolism of a deuterated analogue of the plant hormone S-(+)-abscisic acid. Phytochemistry, 1996,41(1),23-28
[49] M.Perras, P.A.Rose, E.W.Pass; Defining steric, electronic and conformational requirements of carrier-mediated uptate of abscisic acid in barley suspension culture cells. Phytochemistry,1997,46(2),215-222
[50] 丸茂，晋吾，白井；脱落酸类似物与植物生长调节剂．日本专利，JP931001，1991
[51] J.L.Ward, M.H.Beale, Caged plant hormones. Phytochemistry, 1995,36(4), 811-816
[52] L.V.Gusta, The effect of abscisic acid and abscisic acid metabolites on the germination of cressseed. Can. J. Bot., 1992,70(8),1550-1555
[53] M.K.Walker-Simmons,P.A.Rose,A.C.Shaw; The 7'-methyl group of abscisic acid is critical for biological activity in wheat embryo germination. Plant Physiol.; 1994,106,1279-1284
[54] B.T.Miborrow; he effects of synthetic dl-dormin (abscisin Ⅱ) on the growth of oat mesocotyl. Planta; 1966,70,155-158
[55] K.Yamashita, T.Watanabe, M.Watanabe, Studies on abscisic acid. Part ⅩⅥ. Synthesis and biological activity of methyl 3-demethylabscisate and its related analogs. Agric. Biol. Chem.,1982, 46(12), 3069-3073
[56] T. Asami, Y. K.Min, T. Nokano, Synthesis and biological activity of 4'-methoxy derivatives of
abscisic acid. Bioorg. Med. chem. Lett., 2000,10: 1571～1574
[57] S.Tamura, M.Nagao, Synthesis of novel plant growth inhibitors structurally related to abscisic acid. Agr Biol. Chem., 1969,33(2),296-298
[58] S.Tamura, M.Nagao, 5-(1,2-epoxy-2,6,6-trimethyl-1-cyclohex-yl)-3-methyl-cis,trans-2,4-pentadienoic acid and its esters: plant-growth inhibitors structurally related to abscisic acid. planta.,1969,85(2),209-212
[59] S.Tamura, M.Nagao, Synthesis and biological activity of 5-(1-Hydroxy-2,6,6-tri methyl-2-cyclohexen-1-yl)-3-methyl-cis,trans-2,4-pentadienoic ester and somother abscisic acid analogs. Agr. Biol. Chem., 1969, 33(9),1357-1360
[60] Y.Todoroki,S.Nakano,N.Hirai; Ring conformational requirement for biological activity of abscisic acid probed by the cyclopropane analogues. Tetrahedron 1996, 52(24), 8081-8098
[61] T.Oritani,K.Yamashita; Synthesis and biological activity of(±)-2',3'-dihydroabscsic acid. Agric. Biol. Chem.; 1982,46, 817-818
[62] H.Yamamoto,T.Oritani,K.Yamashita; Synthesis of chiral 3'-hydroxy-r-ionylideneacetic acid. Agric. Biol. Chem.; 1988,52,2203-2208
[63] T.J. Blake, E.Bevilacgua, G.A.Hunt, Effects of abscsic and its acetylenic alcohol on dormancy, root development and transpiration in three conifer species. Plant Physiol., 1990,80,371-378
[64] D.C.Walton, in "Abscisic Acid" ed. by F.T.Addicot, praeger, New York, 1983, 1-21
[65] 石德清，盛梓良，吴宏，陈茹玉；2001．O(O，O’-二乙基膦酰基芳基亚甲基)-5-取代苯基-2E,4E-戊二烯酸酯的合成与生物活性研究．35：296～300
[66] 龙姝，陈敏，莫文妍，石德清；2002．N-[甲氧(乙氧)羰基亚甲基]-5-取代苯基-2E，4E-戊二烯酰胺的合成与生物活性研究．36：185～203
[67] 石德清，陈茹玉：2002．含α-氨基膦酸酯的脱落酸类似物的合成与生物活性研究．19：780～783
[68] 吴清来，毛淑芬，覃兆海；脱落酸的全合成．《化学通报》(已录用)
[69] 吴清来，毛淑芬，覃兆海；脱落酸衍生物及类似物研究进展．《植物学通报》(已录用)
[70] 赵中伟，李洪桂，霍广生等；电子等排原理及利用其设计分离试剂的可行性．《中南工业大学学报》，2002，33(6)，584～587
[71] 刘长令：生物电子等排及其在新农药创制中的应用．《农药》，1998，37(2)，1～7
[72] C E Castro, R D Stephens; The Reduction of Multipe Bonds by Low-Valent Transition Metal Ions.The Homogeneous Reduction of Acetylenes by Chromous Sulfate. J.Am.Chem.Soc., 1964,86,4358-4363
[73] Yu G Gololobov, A N Nesmeyanov, V P Lysenko, I E Boldeskul; Twenty-five Years of Dimethylsufoxonium Methylide(Corey's Reagent). tetrahedron, 1987,43(12), 2609～2651
[74] An-Hu Li, Li-Xin Dai, Varinder K Aggarwal; Asymmetric Yielde Reactions: Epoxidation, Cyclopropanation, Aziridination, Olefination, and Rearrangement. Chem. Rev. 1997, 97(6), 2341～2372
[75] A.-H. Li, Y.-G. Zhou, L.-X. Dai, et.al. Asymmetric aziridination over ylidies: highly stereoselective synthesis of acetylenyl-N-sulfonylaziridines. Angew.Chem.,Int.Ed.Engl., 1997, 36(12),1317～1319
[76] W B Austin, N Bilow, W J Kelleghan, K S Y Lau; Fcaile Synthesis of Ethynylated Benzoic Acid Derivatives and Aromatic Compounds via Ethynytrimethylsilane. J. Org. Chem., 1981, 46
(11), 2280～2286;
[77] M Ahmed, G C Barley, M T W Hearn, E R H Jones, V Thaller, J A Yates; Natural Acetylenes. Part XLⅡ. Polyacetylenes from Cultures of the Fungus Fistulina pallida(Berk. And Rev.). J Chem. Soc. Perkin Ⅰ, 1974,1981～1984
[78] Chen Zhao-Gen, Zhou Da-Shun, Zhou Jing-Yao, Wu Shi-Hui; Selectivety of the Reaction for Substituted Propargyl Bromide with Aldehydes Promoted by Metal Tin. Acta Chemica Sinica, 1997,1138～1144;
[79] Michael B. Smith, in "Organic Synthesis" ed. by Kent A.Peterson, praeger, New York,2002, 670～675
[80] 李淑勉，侯守军，李占才等：2，6，6-三甲基-4，4-乙二氧基-2-环己烯-1-酮的合成研究，厦门大学学报(自然科学版)，1999，38，464
[81] 彭美静，俞善信；氯化铁催化合成氯乙酸乙酯，精细化工，1995，12(3)，56～58
[82] 慕长伟；4-[3-(吡啶-4-基)-3-取代苯基丙烯酰]吗啉类化合物的合成及杀菌活性的研究，硕士学位论文，2003，中国农业大学
[83] J R Hanson, E Premuzic; The reduction of organic compounds with chromium(Ⅱ) salts.Angew. Chem.,Int.Ed.Engl., 1968, 7(2), 247～320
[84] 吴清来，毛淑芬，覃兆海；氧化异佛尔酮1位羰基缩酮的选择性合成研究，《化学试剂》(已录用)
[85] 吴清来，毛淑芬，覃兆海；氧化异佛尔酮缩酮化产物的NMR特征，《波谱学杂志》(已录用)
[86] 吴清来，毛淑芬，覃兆海；3-[1-羟基-2，6，6-三甲基-4，4-(乙二氧基)-2-环己烯基]丙炔醇的合成及其稳定性研究，《化学试剂》(已录用)
[87] 郑可利，王贵杰，袁谷；α，β-炔醛异构化高立体选择性合成(2E，4E)-碳十四共轭烯醛．《高等化学学报》，2002，23，855～856
[88] Y Leblanc, B J Fitzimmons, J Adams, et.al. The total synthesis of 12-HETE (12-hydroxyeicosat etraenioc acid) and 12,20-diHETE. J. Org. Chem., 1986, 51(6),789～793
[89] J R Pfister, D V Krishna Murthy; Synthesis of three potential inhibitors of leukotriene biosynthesis. J. Med.Chem., 1983, 26(8), 1099～1103
[90] 邢其毅，徐瑞秋，周政等，《基础有机化学》，高等教育出版社，北京，1993，215～230
[91] 马淳安，《有机电化学合成导论》，科学出版社，北京，2002，205～211
[92] J R Hanson; Applications of chromium(Ⅱ) salts in preparative organic chemistry. Synthesis,1974，1～8
[93] 吴义杰，周明德，刘超美等；碘化三甲基氧化锍的制备．《中国医药工业杂志》，1998，29(3)，129～130
[94] 景肴壁，顾文鑫，任新峰；多取代环丙烷化合物的合成研究．《高等化学学报》，2001，22(10)，1691～1692
[95] 徐明华，林国强：手行金属催化剂在不对称环丙烷化反应中的应用进展．《有机化学》，2000，20(4)，475～485
[96] Yang Tang, Yao-Zeng Huang, Li-Xin Dai, et. al. Cyclopropanation reaction of allylic ylides with α,β-unsaturated esters and amides: tuning of stereoseletivity and the dramatic effect of lithium salts.
J. Org. Chem.. 1996, 61(17), 5762～5769
[97] 周文勇，叶启亮，齐鸣斋等；β-异佛尔酮催化氧化制酮代异佛尔酮，《化学世界》，2002，9，481～483
[98] 赵增国，张松威，耿奎士等，氧化异佛尔酮(3，5，5-三甲基环己烯-1，4-二酮)的合成研究1998，15(4)，42～45
[99] 胡艾希，赵海涛，范国枝等；离子交换树脂催化合成(2R，4R)-酒石酸二甲酯，《湖南大学学报》，1998，25(1)，23～26
[100] I Sakamoto, H Ohrui; Practical synthesis of the disaccharide epitope, D-Galactopyranosyl-α-1,3-D-galactopyranose, by using 1,2;5,6-Di-O-cyclohexylidene-α-D-alactopyranose as the Glycosyl acceptor. Biosci. Biotchnol. Biochem, 2000, 64(9), 1974～1977