非天然氨基酸的合成和双子表面活性剂的合成与性能研究
摘要
本论文包括两个部分：非天然氨基酸的合成与表征和双子表面活性剂的合成与性质研究。
第一部分：许多手性非天然氨基酸是合成多肽、药物和天然产物的中间体。本文以天然的反式-L-羟基脯氨酸为原料，经酯化、氨基保护、羟基活化后叠氮基取代、然后叠氮基还原生成部分保护的手性非天然氨基酸(4S)-1-叔丁氧羰基-4-氨基-L-脯氨酸乙酯，然后水解得到非天然氨基酸(4S)-4-氨基-L-脯氨酸盐酸盐，并对结构进行了表征。
第二部分：合成了2种未见文献报道的酰胺基二苯醚重要中间体，以上面2
This thesis includes two sections:the synthesis of unnatural aromatic amino acids and the synthesis and physics properties of amido diphenyl ether disulfonates Gemini surfactant:
1. (4S)-1-tertbutyloxycarbonyl-4-amino-L-proline methyl ester was prepared from a natural chiral amino acid (4R)-Hydroxy-L-proline via esterfication, protec- tion of amino grop,mesylation,azide displacement and reduction. (4S)- 4-amino-L-proline was prepared (4S)-1-tertbutyloxycarbonyl-4-amino-L-proline methyl ester via hydrolyze. Their structures are identified by IR, 、NMR,、 MS.
第一部分：许多手性非天然氨基酸是合成多肽、药物和天然产物的中间体。本文以天然的反式-L-羟基脯氨酸为原料，经酯化、氨基保护、羟基活化后叠氮基取代、然后叠氮基还原生成部分保护的手性非天然氨基酸(4S)-1-叔丁氧羰基-4-氨基-L-脯氨酸乙酯，然后水解得到非天然氨基酸(4S)-4-氨基-L-脯氨酸盐酸盐，并对结构进行了表征。
第二部分：合成了2种未见文献报道的酰胺基二苯醚重要中间体，以上面2
This thesis includes two sections:the synthesis of unnatural aromatic amino acids and the synthesis and physics properties of amido diphenyl ether disulfonates Gemini surfactant:
1. (4S)-1-tertbutyloxycarbonyl-4-amino-L-proline methyl ester was prepared from a natural chiral amino acid (4R)-Hydroxy-L-proline via esterfication, protec- tion of amino grop,mesylation,azide displacement and reduction. (4S)- 4-amino-L-proline was prepared (4S)-1-tertbutyloxycarbonyl-4-amino-L-proline methyl ester via hydrolyze. Their structures are identified by IR, 、NMR,、 MS.
引文
[1] 张伟国等．氨基酸生产技术及其应用[M]．北京：中国轻工业出版社，1997
[2] 赵维蓉等．化妆品学．合肥：科学技术出版社，1990：56-58
[3] 陶金斐．氨基酸类表面活性剂的制备特性及其应用．1991，1：4-6
[4] 耿愚，倪家宝，冼美明．非天然氨基酸3-(4-噻唑基)-D，L-丙氨酸盐酸盐的合成．氨基酸和生物资源，2000，22(2)：27-29
[5] Desai M. D, Zuckermann R. N, Moos W H, Recent Advances In the Generation of Chemical Diversity Libraries, Drug. Des. Res. 1994,33 (2), 174-188.
[6] Hoffmann R. V, Kim H. O, A Simple Synthesis Approach To Cbl-Phe- W-(Chz)-Gly-Pro-Omean dR elatedP eptideIs osteres, Tetrahedron Lett. 1992, 33 (25), 3579-3582
[7] 郭利，刘刚，挥榴红，多肽类似物-类肽和假肽的研究进展，国外医学．1995， 22(22)，261-2670
[8] 彭师奇，多肽药物化学，科学出版社，1993：49-940
[9] 黄锁义，田华，王加彦，王麟生．含氨基酸的手性化合物外消旋体的制取方法精细化工中间体．2005，34(6)，23-26
[10] 陈英军，张卓标，吕海龙．我国蛋氨酸生产现状及市场分析．精细于专用化学品，2005，13(16)，22-24
[11] 刘云，徐琪寿．氨基酸发酵生产的研究进展．氨基酸和生物资源，1999，21(4)19-23
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[16] CarlosC, MariaDD, JoseAG. Diastereoselecti strecker reaction of imines derived??fromD-glycer-aldehyde. A new route to β-hydroxy- α-aminoaci. Tetrahedron Lett, 1995, 36(16): 2859-2860
[17] EvansDA, BrittonTC, EllmanTA, etal. The asymmetric synthesis of A-aminoacids: eectrophilic azidation of chiral imide enolates, apractical approach to the synthesis of(R)and(S)- α -azidocar boxylicacids. J Am Chem Soc, 1990, 112(1): 4010-4030
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[20] Guichard, G.; Abele, S.; Seebach, D. Preparation of N-Fmoc-protected 2- and 3-amino acids and their use as building blocks for the solid-phase synthesis of -peptides. 1998, 81 (2), 187-206
[21] Vicario J L; Badia D; Carrillo L Asymmetric synthesis of beta-substituted alpha-methyl-beta-amino esters by Mannich reaction of (S, S)-(+)-pseudoephedrine acetamide derived enolate with imines. Organic letters (2001), 3(5), 773-776.
[22] Nelson S G; Spencer K L Sequential acyl halide-aldehyde cyclocondensation and enzymatic resolution as a route to enantiomerically enriched beta-lactones. The Journal of organic chemistry (2000), 65(4), 1227-1230.
[23] 于平．生物转化和手性拆分技术制备D-氨基酸研究进展．生物学通报 2005，40(9)，3-5
[24] 李俊，蔡水洪，朱中南，赵玲．手性化合物的萃取拆分研究．化学世界， 2001，42(5)，233-236
[25] Bowman, N. S.; McCloud, G. T.; Schweitzer, G. K. Partial resolutionn of some organic racemates by solvent extraction. Journal of the American Chemical Society 1968, 90(14), 3848-3852.
[26] TakeuchiT, HorikawaR. Enantioselective solventextracti of neutral D, L-amino acids intwo-phase systems containg N-n-alkyl-proline derivatives and copper??(Ⅱ)ion Analytic Chemistry, 1984, 56: 1152-1155.
[27] 何仕国，俞一军，许文松．DL-苯丙氨酸的酶法拆分研究．化学反应工程与工艺，2004，20(1)，64-68
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[29] 曾苏，章立，沈向忠，刘志强．色谱[J]，1994，12(4)：259．
[30] 陈晓，龙韫先，邓峰杰．薄层色谱在有机物顺反及对应异构体分离中的应用． 化学研究与应用，1999，11(5)，552-554
[31] 翁家宝．β-环糊精固载相薄层层析法直接拆分氨基酸D，L一对映体．福建师范大学学报(理学版)，1996，12(3)，31-35
[32] 李英杰，高立娣．水溶性B-CD聚合物在毛细管电泳中分离氨基酸对映体．分析实验室，2005，24(12)，51-54
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[34] 高春生，赵守孝．胶束动电毛细管色谱在旋光异构体拆分中的应用．国外医学药学分册．1994，2l(3)：170-174
[35] Cohen, A. S.; Paulus, A.; Karger, B. L. High-performance capillary electrophoresis using open tubes and gels. Chromatographia, 1987, 24, 15-24.
[36] 京兰，钱小红．亲和毛细管电泳技术及其应用．色谱．1999，17(4)：342-345
[37] 黄锁义，王麟生．N-Boc-3-碘代-L-丙氨酸甲酯的合成研究．化工技术与开发，2004，33(2)：13-15
[38] Stephen Thompson, garret Kalindjianb. The synthesis and biological activity of C2-fluorinated pyrrolo[2, 1-c][1, 4]benzodiazepines. Tetrahedron Letters, 2003, 44(42), 7809-7812
[39] Matthew A, Williams, Hery Rapoport. Synthesis of Constrained DTPA Analogues Incorporation of the Ethylenddiamine Units as Aminopyrrolidines. J. Orm. Chem. 1994, 59(13), 3616-3625
[40] 钟传蓉，黄荣华，代华．水溶性疏水缔合物单体的合成．化学世界，2004，45??(8), 437-441
[41] MakotoTamaki, Guoxia Han and Victor J Hruby. Practical and Efficient Synthesis of Orthogonally Protected Constrained 4-Guanidinoprolines. J. Org. Chem. 2001, 66(3), 1038-1042
[42] 朱步瑶，赵国玺．精细化工，1985，2(4)，1-4
[43] 赵国玺．表面活性剂物理化学．北京大学出版社，1984，24l-249，270-286．
[44] Meguro K etal in Nonionic surfactants, Physical Chemistry Surfactants Science Series 23, Mercel, Dekker Inc, 1987, 138.
[45] Szejtli. J. Cyclodextrin Technology. Kluwer Academic Publisher: Dordrdcht. 1988
[46] Zhu Y-P, Masuyama A, KiritoY-I etal M J Am. Oil Chem. Soc., 1992, 69(7), 626-632
[47] Borse M, Sharma V. Effect of head group polarity and spacer chain length on the aggregation properties of gemini surfactants in an aquatic environment Journal of Colloidand Interface Science, 2005, 284: 282-288.
[48] 刘德荣．表面活性剂的合成与应用．四川科学技术出版社．1987，221-226
[49] Tsuchihashi G, Ori A, Honda Y, A General synthetic method of chiral 2-arylalkanoic esters viathermal 1, 2-rearrangement. Bull Chem Soc Jpn, 1987, 60, 1027
[50] Happel, G, Mathiasch, B, Kammerer, H. Bis calyx [4] arene -Zn- tetraaryl porphyrines. Makromol. Chem. 1975, 176(2), 3317
[51] Tsuchihashi G, Ori A, Honda Y, A General synthetic method of chiral 2"arylalkanoic esters viathermal 1, 2-rearrangement, Bull Chem Soc Jpn, 1987, 60(2), 1027
[52] Chen K D. Separation of ergot alkaloids by micellar electrokinetic capillary chromatography using cationic Gemini surfactants. Journal of Chromatography A, 1998, 822(2): 281-290
[53] Fredric M M, Jason S K. Angew. Chem. Int, Ed., 2000, 39: 1906-1920
[54] Bohmer, V. Calixarenes, Macrocycles with Unlimited Possibilities. Angew. Chem. Int. Ed. Engl. 1995, 34(2), 713.
[55] Zh P, Masuyama Y, Nagata T, Preparation and properties of double chain??surfactants being twosulfonate groups. J. Jpn. Oil Chem. Soc. 1991, (40), 473～477
[56] Konno, A., Misaki, M., Toda, J, Wada, T, Yasumatsu, K. Bitterness Reduction of naringin and limonin by β-cyclodextrin. Agric. Biol. Chem. 1986, 46(2), 2203
[57] 王俊，杨培法，李杰，李翠勤．阳离子型双子表面活性剂的合成及表面活性应用化工，2005，34(11)，692-694
[58] 赵忠奎，乔卫红，李宗石．Gemini表面活性剂[J]．化学通报 2002，65：1-5．
[59] 王云斐，刘云．Gemini型表面活性剂的合成进展．精细化工，2004，21(2) 98-111
[60] Shinkai. S. Calixarenes-The Third Generation of Supramolecules. Tetrahedron 1993, 49, 8933
[61] 姚蒙正，程侣伯，王家儒．精细化工产品合成原理[M]．北京：中国石化出版社，1992．290-291．
[62] 苏瑜，马德桴，薛仲华．十二烷基二苯醚双磺酸盐的合成[J]．精细化工， 2002(19)：443-445．
[63] M. J. Rosen, L. D. Song. Dynamic Surface Tension of Aqueous Surfactant Solutions 8. Effect of Spacer on Dynamic Properties of Gemini Surfactant Solutions. J. Collod. Interface Sci. 1996, 179: 261-268
[2] 赵维蓉等．化妆品学．合肥：科学技术出版社，1990：56-58
[3] 陶金斐．氨基酸类表面活性剂的制备特性及其应用．1991，1：4-6
[4] 耿愚，倪家宝，冼美明．非天然氨基酸3-(4-噻唑基)-D，L-丙氨酸盐酸盐的合成．氨基酸和生物资源，2000，22(2)：27-29
[5] Desai M. D, Zuckermann R. N, Moos W H, Recent Advances In the Generation of Chemical Diversity Libraries, Drug. Des. Res. 1994,33 (2), 174-188.
[6] Hoffmann R. V, Kim H. O, A Simple Synthesis Approach To Cbl-Phe- W-(Chz)-Gly-Pro-Omean dR elatedP eptideIs osteres, Tetrahedron Lett. 1992, 33 (25), 3579-3582
[7] 郭利，刘刚，挥榴红，多肽类似物-类肽和假肽的研究进展，国外医学．1995， 22(22)，261-2670
[8] 彭师奇，多肽药物化学，科学出版社，1993：49-940
[9] 黄锁义，田华，王加彦，王麟生．含氨基酸的手性化合物外消旋体的制取方法精细化工中间体．2005，34(6)，23-26
[10] 陈英军，张卓标，吕海龙．我国蛋氨酸生产现状及市场分析．精细于专用化学品，2005，13(16)，22-24
[11] 刘云，徐琪寿．氨基酸发酵生产的研究进展．氨基酸和生物资源，1999，21(4)19-23
[12] 孙志贤．现代生物化学与研究技术[M]，北京：军事医学科学出版社，1993
[13] 惠永正，陈耀全．化学与生命科学[M]．北京：化学工业出版社，1992：38
[14] 姜忠义，陈洪钫．苯丙氨酸光学异构体的酶法拆分．应用化学，2001，18(3)， 231-232
[15] SchoelkopfU, Busse U,Kilger R, etal. Asymmetric cyntheses via heterocyclic intermediates; ⅩⅪ: Enantioselective synthesis of α -alkylleucine methylestersusingthebislactimetherofcyclo(L- Leu-L-Leu) as starting material. Synthesis, 1984, 32(3), 271-274
[16] CarlosC, MariaDD, JoseAG. Diastereoselecti strecker reaction of imines derived??fromD-glycer-aldehyde. A new route to β-hydroxy- α-aminoaci. Tetrahedron Lett, 1995, 36(16): 2859-2860
[17] EvansDA, BrittonTC, EllmanTA, etal. The asymmetric synthesis of A-aminoacids: eectrophilic azidation of chiral imide enolates, apractical approach to the synthesis of(R)and(S)- α -azidocar boxylicacids. J Am Chem Soc, 1990, 112(1): 4010-4030
[18] Leonard, F, Wajngurt, A, Klein. M, Smith. C. M. Cetraliy active 2-(substituted phenyl)- β-aminobutyric acids. J. Org. Chem, 1961, 26, 4062-4065
[19] Suda, H.; Takita, T.; Aoyagi, T.; Umezawa, H. The structure of bestatin. The J. of Antibiolics, 1976, 29(1), 100-101
[20] Guichard, G.; Abele, S.; Seebach, D. Preparation of N-Fmoc-protected 2- and 3-amino acids and their use as building blocks for the solid-phase synthesis of -peptides. 1998, 81 (2), 187-206
[21] Vicario J L; Badia D; Carrillo L Asymmetric synthesis of beta-substituted alpha-methyl-beta-amino esters by Mannich reaction of (S, S)-(+)-pseudoephedrine acetamide derived enolate with imines. Organic letters (2001), 3(5), 773-776.
[22] Nelson S G; Spencer K L Sequential acyl halide-aldehyde cyclocondensation and enzymatic resolution as a route to enantiomerically enriched beta-lactones. The Journal of organic chemistry (2000), 65(4), 1227-1230.
[23] 于平．生物转化和手性拆分技术制备D-氨基酸研究进展．生物学通报 2005，40(9)，3-5
[24] 李俊，蔡水洪，朱中南，赵玲．手性化合物的萃取拆分研究．化学世界， 2001，42(5)，233-236
[25] Bowman, N. S.; McCloud, G. T.; Schweitzer, G. K. Partial resolutionn of some organic racemates by solvent extraction. Journal of the American Chemical Society 1968, 90(14), 3848-3852.
[26] TakeuchiT, HorikawaR. Enantioselective solventextracti of neutral D, L-amino acids intwo-phase systems containg N-n-alkyl-proline derivatives and copper??(Ⅱ)ion Analytic Chemistry, 1984, 56: 1152-1155.
[27] 何仕国，俞一军，许文松．DL-苯丙氨酸的酶法拆分研究．化学反应工程与工艺，2004，20(1)，64-68
[28] 吕海涛，云自厚．脲衍生物型手性固定相分离a-氨基酸对映体的研究．色谱，1995，13(1)：8-11
[29] 曾苏，章立，沈向忠，刘志强．色谱[J]，1994，12(4)：259．
[30] 陈晓，龙韫先，邓峰杰．薄层色谱在有机物顺反及对应异构体分离中的应用． 化学研究与应用，1999，11(5)，552-554
[31] 翁家宝．β-环糊精固载相薄层层析法直接拆分氨基酸D，L一对映体．福建师范大学学报(理学版)，1996，12(3)，31-35
[32] 李英杰，高立娣．水溶性B-CD聚合物在毛细管电泳中分离氨基酸对映体．分析实验室，2005，24(12)，51-54
[33] Gassmann, E.; Kuo, J. E.; Zare, R. N. Electrokinetic separation of chiral compounds. Science (1985), 230(4727), 813-814.
[34] 高春生，赵守孝．胶束动电毛细管色谱在旋光异构体拆分中的应用．国外医学药学分册．1994，2l(3)：170-174
[35] Cohen, A. S.; Paulus, A.; Karger, B. L. High-performance capillary electrophoresis using open tubes and gels. Chromatographia, 1987, 24, 15-24.
[36] 京兰，钱小红．亲和毛细管电泳技术及其应用．色谱．1999，17(4)：342-345
[37] 黄锁义，王麟生．N-Boc-3-碘代-L-丙氨酸甲酯的合成研究．化工技术与开发，2004，33(2)：13-15
[38] Stephen Thompson, garret Kalindjianb. The synthesis and biological activity of C2-fluorinated pyrrolo[2, 1-c][1, 4]benzodiazepines. Tetrahedron Letters, 2003, 44(42), 7809-7812
[39] Matthew A, Williams, Hery Rapoport. Synthesis of Constrained DTPA Analogues Incorporation of the Ethylenddiamine Units as Aminopyrrolidines. J. Orm. Chem. 1994, 59(13), 3616-3625
[40] 钟传蓉，黄荣华，代华．水溶性疏水缔合物单体的合成．化学世界，2004，45??(8), 437-441
[41] MakotoTamaki, Guoxia Han and Victor J Hruby. Practical and Efficient Synthesis of Orthogonally Protected Constrained 4-Guanidinoprolines. J. Org. Chem. 2001, 66(3), 1038-1042
[42] 朱步瑶，赵国玺．精细化工，1985，2(4)，1-4
[43] 赵国玺．表面活性剂物理化学．北京大学出版社，1984，24l-249，270-286．
[44] Meguro K etal in Nonionic surfactants, Physical Chemistry Surfactants Science Series 23, Mercel, Dekker Inc, 1987, 138.
[45] Szejtli. J. Cyclodextrin Technology. Kluwer Academic Publisher: Dordrdcht. 1988
[46] Zhu Y-P, Masuyama A, KiritoY-I etal M J Am. Oil Chem. Soc., 1992, 69(7), 626-632
[47] Borse M, Sharma V. Effect of head group polarity and spacer chain length on the aggregation properties of gemini surfactants in an aquatic environment Journal of Colloidand Interface Science, 2005, 284: 282-288.
[48] 刘德荣．表面活性剂的合成与应用．四川科学技术出版社．1987，221-226
[49] Tsuchihashi G, Ori A, Honda Y, A General synthetic method of chiral 2-arylalkanoic esters viathermal 1, 2-rearrangement. Bull Chem Soc Jpn, 1987, 60, 1027
[50] Happel, G, Mathiasch, B, Kammerer, H. Bis calyx [4] arene -Zn- tetraaryl porphyrines. Makromol. Chem. 1975, 176(2), 3317
[51] Tsuchihashi G, Ori A, Honda Y, A General synthetic method of chiral 2"arylalkanoic esters viathermal 1, 2-rearrangement, Bull Chem Soc Jpn, 1987, 60(2), 1027
[52] Chen K D. Separation of ergot alkaloids by micellar electrokinetic capillary chromatography using cationic Gemini surfactants. Journal of Chromatography A, 1998, 822(2): 281-290
[53] Fredric M M, Jason S K. Angew. Chem. Int, Ed., 2000, 39: 1906-1920
[54] Bohmer, V. Calixarenes, Macrocycles with Unlimited Possibilities. Angew. Chem. Int. Ed. Engl. 1995, 34(2), 713.
[55] Zh P, Masuyama Y, Nagata T, Preparation and properties of double chain??surfactants being twosulfonate groups. J. Jpn. Oil Chem. Soc. 1991, (40), 473～477
[56] Konno, A., Misaki, M., Toda, J, Wada, T, Yasumatsu, K. Bitterness Reduction of naringin and limonin by β-cyclodextrin. Agric. Biol. Chem. 1986, 46(2), 2203
[57] 王俊，杨培法，李杰，李翠勤．阳离子型双子表面活性剂的合成及表面活性应用化工，2005，34(11)，692-694
[58] 赵忠奎，乔卫红，李宗石．Gemini表面活性剂[J]．化学通报 2002，65：1-5．
[59] 王云斐，刘云．Gemini型表面活性剂的合成进展．精细化工，2004，21(2) 98-111
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