二苯砜对环蕃及氮杂环二茂铁磺酰的合成、修饰、生物活性研究
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摘要
酶催化作用的模拟是一个富有挑战性的研究领域,激发着化学家,尤其是生物有机化学家的浓厚兴趣。四氮杂环蕃是人工模拟酶研究过程中发现的一类新化合物,也是主客体化学中可以充当主体的一类重要化合物。作为人工模拟酶,利用它本身所具有疏水性空腔,根据环的形状、大小及静电作用的不同,俘获不同种类的有机分子,形成主客体包结络合物,从而可选择性地控制反应、提高反应速率。通过改变氮杂环蕃化合物的形状以及引入活性基团,构成具有协同包结和多重识别功能的活性中心,形成不同包结性能的主体,与客体形成超分子体系,实现酶功能模拟和分子识别。论文第一部分对超分子化学、环蕃、氮杂环蕃及二茂铁环蕃的研究进展进行了简介。第二部分报道了一种未见文献报道的新型氮杂环蕃:1,6,20,25-四氮杂[6.1.6.1]对环蕃-13,32-二苯砜,并用二茂铁磺酰氯对其进行了修饰。
二茂铁及其衍生物在各个领域的作用愈来愈受到人们的重视,尤其是在医药、生化、燃料、催化剂等领域已有广泛的应用。论文第三部分选择了氮杂环化合物吲哚、吗啉、咪唑、苯并三唑、六水合哌嗪、苯并咪唑衍生物分别与具有较强生物活性的二茂铁磺酰氯反应,制得了十一种未见文献报道的氮杂环取代的二茂铁磺酰胺衍生物,并用IR、~1H NMR进行了表征。对部分产物进行了生物活性测试。
论文第四部分合成了荧光材料的中间体,得到了一种未见文献报道的中间体晶体结构,对此晶体结构进行了报道。
Enzyme catalysia simulation is rich in a challenge scitific research, which arouse the curiosity of chemist especially bio-organic chemist. Azaparacyclophane is a new kind of compound which is found in the study of artificial simulation. It can also act as host compound in the host-guest chemistry. As artificial enzymes, using hydrophobic cavities, they can capture different organic molecule to form the host-guest system, based on the difference of the ring site, size and interaction. Azaparacyclophane play a significant role in the simulation of enzyme function in some organic reaction system to mimic the binding of substrates and catalyze the reaction, consequently control the reaction specially and increase the reaction velocity. By changing the ring site and size or modifying the cyclophane with the active unit, we can design the novel active center with coordinated inclusion and multirecognition to get the special host, which would form the supramolecular system with the guest and actualize the molecular recognition and the simulation of enzyme function. In the part 1, a brief introduction of the research progress of supramolecule chemistry、 cyclophane. azaparacyclophane and ferrocenophane is provided. In the part 2, a never reported kind of azaparacyclophane: 1,6,20,25-tetraaza[6.1.6.1] paracyclophane-13,32-disulfone is synthesized and decorated with ferrocenesulfonyl chloride. The application of ferrocene and its derivatives have been attracted more and more attentions in many domains, especially have been widely used in the fields of medicine, biochemistry, fuel and catalyzer. In the part 3, nitrogen heterocycles indole、 morpholine、 imidazole、 1,2,3,-benzotriazole、 piperazine six hydrate、 benzimidazole derivatives is designed to react with ferrocenesulfonyl chloride respectively and eleven new nitrogen heterocyclic ferrocenesulfonyl derivatives are synthesized from ferrocenesulfonyl chloride and the nitrogen heterocycles, confirmed by IR, ~1H NMR and Elemental analysis.In the part 4, the crystal structure of one novel midst system, which was gotten in the synthesis of fluorescene material and had never been reported is presented.
二茂铁及其衍生物在各个领域的作用愈来愈受到人们的重视,尤其是在医药、生化、燃料、催化剂等领域已有广泛的应用。论文第三部分选择了氮杂环化合物吲哚、吗啉、咪唑、苯并三唑、六水合哌嗪、苯并咪唑衍生物分别与具有较强生物活性的二茂铁磺酰氯反应,制得了十一种未见文献报道的氮杂环取代的二茂铁磺酰胺衍生物,并用IR、~1H NMR进行了表征。对部分产物进行了生物活性测试。
论文第四部分合成了荧光材料的中间体,得到了一种未见文献报道的中间体晶体结构,对此晶体结构进行了报道。
Enzyme catalysia simulation is rich in a challenge scitific research, which arouse the curiosity of chemist especially bio-organic chemist. Azaparacyclophane is a new kind of compound which is found in the study of artificial simulation. It can also act as host compound in the host-guest chemistry. As artificial enzymes, using hydrophobic cavities, they can capture different organic molecule to form the host-guest system, based on the difference of the ring site, size and interaction. Azaparacyclophane play a significant role in the simulation of enzyme function in some organic reaction system to mimic the binding of substrates and catalyze the reaction, consequently control the reaction specially and increase the reaction velocity. By changing the ring site and size or modifying the cyclophane with the active unit, we can design the novel active center with coordinated inclusion and multirecognition to get the special host, which would form the supramolecular system with the guest and actualize the molecular recognition and the simulation of enzyme function. In the part 1, a brief introduction of the research progress of supramolecule chemistry、 cyclophane. azaparacyclophane and ferrocenophane is provided. In the part 2, a never reported kind of azaparacyclophane: 1,6,20,25-tetraaza[6.1.6.1] paracyclophane-13,32-disulfone is synthesized and decorated with ferrocenesulfonyl chloride. The application of ferrocene and its derivatives have been attracted more and more attentions in many domains, especially have been widely used in the fields of medicine, biochemistry, fuel and catalyzer. In the part 3, nitrogen heterocycles indole、 morpholine、 imidazole、 1,2,3,-benzotriazole、 piperazine six hydrate、 benzimidazole derivatives is designed to react with ferrocenesulfonyl chloride respectively and eleven new nitrogen heterocyclic ferrocenesulfonyl derivatives are synthesized from ferrocenesulfonyl chloride and the nitrogen heterocycles, confirmed by IR, ~1H NMR and Elemental analysis.In the part 4, the crystal structure of one novel midst system, which was gotten in the synthesis of fluorescene material and had never been reported is presented.
引文
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[2] 刘育,尤长城,张衡益,《超分子化学—合成受体的分子识别与组装》,2001,南开大学出版社
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[5] 史真,《现代杂环化学选论》,陕西科学技术出版社,1996
[6] Vogtle F,《超分子化学》 1995
[7] Hilggenfeld R., Saenger W., Angew. Chem.,Int. Ed. Engl, 1982, 21:787-788
[8] a) Odashima K, Iitaka Y., Koga K., J. Am. Chem. Soc. 1980, 102:2504. b) Odashima K., Itai A., Iitaka Y., Koga K., J. Org. Chem. 1985, 50: 4478～4484.
[9] J.M. Lehn. Angew. Chem. Int. Ed. Engl. 1989, 27:89
[10] 白银娟,史真,《大环化学和超分子化学研究进展论文选集》,西北大学出版社,1994
[11] Odamshima K., Itai A., Iitaka Y., et.al., Tetrahedron Lett., 1980, 21:4347
[12] Dickert F, Haunschild A., Reif M., Adv.Mater. 1993, 5:277-279
[13] Mod K, Odashima K., Itai A., Heterocycles, 1984, 21:388
[14] Odashima K., Koga K., Heterocycles. 1981, 15(2):1151-4
[15] Chung-Fang Lai, Odashima K., Koga K., Tetrahedron Lett. 1985, 26(42):5179-5182.
[16] Murakami Y., Ohno T., Hayashida O., J. Chem. Soc., Chem. Commun., 1991,950-952
[17] Shino T., J. Chromatory.A, 2000, 877:61～69.
[18] Kikuchi, J. Supram. Chem, 2001, 1:275～281.
[19] Webb T. H., Wilcox C. S., Chem. Soc. Rev., 1993, 22(6): 383～395
[20] Lehn J.M., Angew.Chem. Int Ed. Engl., 1988, 27(1):89-112
[21] WANG Chuan-Zhang(王传忠), ZHU Zhi-ang(朱志昂), LI Ying(李瑛) et al., Chem. J. Chinese Universities(高等学校化学学报), 2001, 22(2):262-264
[22] LIU Yu(刘育), YOU Chang-Cheng(尤长城). Chem. J. Chinese Universities(高等学校化学学报), 2001, 22(4): 591-597
[23] 岳红,《高等无机化学》,机械工业出版社,2002
[24] D.J. Cram, H. J. Steinberg. J. Am. Chem. Soc.,1951, 73: 5691-5704.
[25] Diederich F, cyclophane, Stoddar, J. F., Ed., Monographs in supramolecular Chemistry, The Royal Society of Chemistry, Cambridge, 1991.
[26] 史真,王建华,有枧化学,1993,13:113～121
[27] 高勇,史真,化学通报,2004,67(4):w026
[28] 史真.现代在环化学选论.西安:陕西科学技术出版社,1998:131-189.
[29] 白银娟,苏玉婵,史真.大环化学和超分子化学研究进展.西安:西北大学出版社,2002:143-146
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[31] Ron Rulkens, Derek P. Gates, David Balaishis, John K. Pudelski, Douglas F. Mcintosh, Alan J. Lough, and Ian Manners. J. Am. Chem. Soc, 1997, 119, 10976-10986.
[32] John B. Sheridan, Karen Temple, Alan J. Lough and Ian Manners. J. Chem. Soc, Dalton. Trans., 1997, 711-713.
[33] 王学杰,王立.化学进展,2002,14(6),486-492.
[34] Patrick. Lipau, Takashi Seki, Gerald Kehr, Alexandra Abele, Roland Frohlich, Gerhand Erker and Stefen Grimme. Organometallics, 2003, 22, 2226-2232.
[35] Stenfan Zurcher, Volker Gramlich, Antonio Togni. Inorganica Chimica Acta, 1999, 291, 355-364.
[36] W. P. Freeman, A. L. Rheingold, R. L. Ostrander, T. D. Tilley, Anrew. Chem., 1993, 105, 1841.
[37] W. P. Freeman, T. D. Tilley, J. Am. Chem. Soc., 1994, 116, 8428.
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[40] M. Hobi, G. Rihs, G. Rist, A. Albinati, P. Zanello, D. Zech, H. Keller, A. Togni, Organometallics, 1994, 13, 1224.
[41] M. Hobi, G. S. Zurcher, V. Gramlich, U. Burckhardt, C. Mensing, m. Spahr, A. Togni, Organometallics, 1996, 15, 5342.
[42] M. Hobi, O. Ruppert, V. Gramlich, A. Togni, Organometallics, 1997, 16, 1384.
[43]S. Zurcher, V. Gramlich, D. Von arx, A. Togni, Inorg. Chem., 1998, 37,4015.
[44] M. J. Gerry Lesley, Ulricke Mock, Nicholas C. Norman, A. Guy Orpen, Craig. R. Rice, Jonath and Starbuck. Journal of Organometallic Chemistry, 1999, 582,116-118.
[45]W. Finck, B. Z. Tang, D. A. Foucher, D. B. Zamble, R. Ziembinski, A. Lough, J. Manneers, Organometallics, 1993,12, 823.
[46] V. V. Dement'ev, F. Cervantes-Lee, L Parkanyi, H. Sharma, K. H. Pannel, M. T. Nguyen, A. Diaz, Organometallics, 1993,12,1987.
[47] H. Stoeckli-Evans, A. G Osbourne, R. H. Whitely, J. Organomet. Chem., 1980,194, 91.
[48] M. Burkexlaing, K. N. Trueblood, Acta Crystallogr, 1965,19, 373.
[49]J..M. Nelson, H. Rengel, I. Manners, J. Am. Chem. Soc. ,1993,115,7035.
[50] K. Hafner, C. Mink, H. J. Lindner, Angew. Chem. Int. Ed. Engl., 1994, 33,1479
[51]R. Rulkens, A. J. Lough, I. Manners, Angew. Chem. Int. Ed. Engl., 1996, 35,1805.
[52] M. Herberhold, U. Steffi, W. Milius, B. Wrackmeyer, Angew. Chem. Int. Ed. Engl. 1996,35,1803.
[53]I. Manners, Can, J. Chem., 1998,76,371.
[54]H. Braunschweig, R. Dirk, M. Muller, P. Nguyen, R. Resendes, D. P. Gates, I. Manners, Angew. Chem. Int. Ed. Engl., 1997,36,2338.
[55] M. Herberhold, U. Dorfler, B. Wrackmeyer, J. Organomet. Chem. 1997, 530,117.
[56] Stephanie Kmippel, Roland Frohlich, Gerhard Erker. Journal of Organometallic Chemistry, 1999, 586, 218-222.
[57]Cheikh M. N'Diaye, Lucien A. Maciejewski, Jacques S. Brocard and Christophe Biot. Tetrahedron letters, 2001,42, 7221-7223.
[58]P. Molina, A. Tarraga, D. Curiel, M. D. Velasco. Journal of Organometallic Chemistry, 2001, 637-639, 258-265.
[59]傅恩琴,王国超,薛鹏,高翠琴,吴成泰.化学通报, 1999,5,20-25.
[60] Patrick Liptau, Stephanie Knuppel, Gerald Kehr, Olga Kataeva, Roland Frohlich, Gerhard Erker. Journal of Organometallic Chemistry, 2001, 621-630.
[61] Andrew J. Locke and Chjristopher J. Richards. Organometallics, 1999,18,3750-3759.
[62]Andrew J. Locke, Claire Jones, and Chjristopher J. Richards. Journal of Organometallic Chemistry, 2001,637-639, 669-676.
[63]Bernd Wrackmeyer, Elena V. Klimkina and Wolfgang Milius. Inorganic Chemistry Communications, 2004,7,412-416.
[64]Toshiyuki Moriuchi, Seiji Bandoh, Yoko Miyaji, Toshikazu Hirao, Journal of Organometallic Chemistry, 2000,599,135-142.
[65]T. Moriuchi, I. Ikeda, Organometallics, 1995,14,3578.
[2] 刘育,尤长城,张衡益,《超分子化学—合成受体的分子识别与组装》,2001,南开大学出版社
[3] Diederich,F, "Cyclophane", Stoddart, J. E, Ed., Monographs in Supramolecular Chemistry, The Royal Society of Chemistry, Cambridge, 1991.
[4] Schneider H.J., Angew Chem Int Ed Engl, 1991, 30:1417-1436.
[5] 史真,《现代杂环化学选论》,陕西科学技术出版社,1996
[6] Vogtle F,《超分子化学》 1995
[7] Hilggenfeld R., Saenger W., Angew. Chem.,Int. Ed. Engl, 1982, 21:787-788
[8] a) Odashima K, Iitaka Y., Koga K., J. Am. Chem. Soc. 1980, 102:2504. b) Odashima K., Itai A., Iitaka Y., Koga K., J. Org. Chem. 1985, 50: 4478～4484.
[9] J.M. Lehn. Angew. Chem. Int. Ed. Engl. 1989, 27:89
[10] 白银娟,史真,《大环化学和超分子化学研究进展论文选集》,西北大学出版社,1994
[11] Odamshima K., Itai A., Iitaka Y., et.al., Tetrahedron Lett., 1980, 21:4347
[12] Dickert F, Haunschild A., Reif M., Adv.Mater. 1993, 5:277-279
[13] Mod K, Odashima K., Itai A., Heterocycles, 1984, 21:388
[14] Odashima K., Koga K., Heterocycles. 1981, 15(2):1151-4
[15] Chung-Fang Lai, Odashima K., Koga K., Tetrahedron Lett. 1985, 26(42):5179-5182.
[16] Murakami Y., Ohno T., Hayashida O., J. Chem. Soc., Chem. Commun., 1991,950-952
[17] Shino T., J. Chromatory.A, 2000, 877:61～69.
[18] Kikuchi, J. Supram. Chem, 2001, 1:275～281.
[19] Webb T. H., Wilcox C. S., Chem. Soc. Rev., 1993, 22(6): 383～395
[20] Lehn J.M., Angew.Chem. Int Ed. Engl., 1988, 27(1):89-112
[21] WANG Chuan-Zhang(王传忠), ZHU Zhi-ang(朱志昂), LI Ying(李瑛) et al., Chem. J. Chinese Universities(高等学校化学学报), 2001, 22(2):262-264
[22] LIU Yu(刘育), YOU Chang-Cheng(尤长城). Chem. J. Chinese Universities(高等学校化学学报), 2001, 22(4): 591-597
[23] 岳红,《高等无机化学》,机械工业出版社,2002
[24] D.J. Cram, H. J. Steinberg. J. Am. Chem. Soc.,1951, 73: 5691-5704.
[25] Diederich F, cyclophane, Stoddar, J. F., Ed., Monographs in supramolecular Chemistry, The Royal Society of Chemistry, Cambridge, 1991.
[26] 史真,王建华,有枧化学,1993,13:113～121
[27] 高勇,史真,化学通报,2004,67(4):w026
[28] 史真.现代在环化学选论.西安:陕西科学技术出版社,1998:131-189.
[29] 白银娟,苏玉婵,史真.大环化学和超分子化学研究进展.西安:西北大学出版社,2002:143-146
[30] Richard W, Heo, T. Randall Lee, Journal of Organometallic Chemistry, 1999, 578, 31-42.
[31] Ron Rulkens, Derek P. Gates, David Balaishis, John K. Pudelski, Douglas F. Mcintosh, Alan J. Lough, and Ian Manners. J. Am. Chem. Soc, 1997, 119, 10976-10986.
[32] John B. Sheridan, Karen Temple, Alan J. Lough and Ian Manners. J. Chem. Soc, Dalton. Trans., 1997, 711-713.
[33] 王学杰,王立.化学进展,2002,14(6),486-492.
[34] Patrick. Lipau, Takashi Seki, Gerald Kehr, Alexandra Abele, Roland Frohlich, Gerhand Erker and Stefen Grimme. Organometallics, 2003, 22, 2226-2232.
[35] Stenfan Zurcher, Volker Gramlich, Antonio Togni. Inorganica Chimica Acta, 1999, 291, 355-364.
[36] W. P. Freeman, A. L. Rheingold, R. L. Ostrander, T. D. Tilley, Anrew. Chem., 1993, 105, 1841.
[37] W. P. Freeman, T. D. Tilley, J. Am. Chem. Soc., 1994, 116, 8428.
[38] P. Jutzi, A. Karl, P. Hofmann, Angew. Chem., 1980, 92, 496.
[39] P. Jutzi, A. Karl, C. Burschka, J. Organomet. Chem., 1981, 215, 27.
[40] M. Hobi, G. Rihs, G. Rist, A. Albinati, P. Zanello, D. Zech, H. Keller, A. Togni, Organometallics, 1994, 13, 1224.
[41] M. Hobi, G. S. Zurcher, V. Gramlich, U. Burckhardt, C. Mensing, m. Spahr, A. Togni, Organometallics, 1996, 15, 5342.
[42] M. Hobi, O. Ruppert, V. Gramlich, A. Togni, Organometallics, 1997, 16, 1384.
[43]S. Zurcher, V. Gramlich, D. Von arx, A. Togni, Inorg. Chem., 1998, 37,4015.
[44] M. J. Gerry Lesley, Ulricke Mock, Nicholas C. Norman, A. Guy Orpen, Craig. R. Rice, Jonath and Starbuck. Journal of Organometallic Chemistry, 1999, 582,116-118.
[45]W. Finck, B. Z. Tang, D. A. Foucher, D. B. Zamble, R. Ziembinski, A. Lough, J. Manneers, Organometallics, 1993,12, 823.
[46] V. V. Dement'ev, F. Cervantes-Lee, L Parkanyi, H. Sharma, K. H. Pannel, M. T. Nguyen, A. Diaz, Organometallics, 1993,12,1987.
[47] H. Stoeckli-Evans, A. G Osbourne, R. H. Whitely, J. Organomet. Chem., 1980,194, 91.
[48] M. Burkexlaing, K. N. Trueblood, Acta Crystallogr, 1965,19, 373.
[49]J..M. Nelson, H. Rengel, I. Manners, J. Am. Chem. Soc. ,1993,115,7035.
[50] K. Hafner, C. Mink, H. J. Lindner, Angew. Chem. Int. Ed. Engl., 1994, 33,1479
[51]R. Rulkens, A. J. Lough, I. Manners, Angew. Chem. Int. Ed. Engl., 1996, 35,1805.
[52] M. Herberhold, U. Steffi, W. Milius, B. Wrackmeyer, Angew. Chem. Int. Ed. Engl. 1996,35,1803.
[53]I. Manners, Can, J. Chem., 1998,76,371.
[54]H. Braunschweig, R. Dirk, M. Muller, P. Nguyen, R. Resendes, D. P. Gates, I. Manners, Angew. Chem. Int. Ed. Engl., 1997,36,2338.
[55] M. Herberhold, U. Dorfler, B. Wrackmeyer, J. Organomet. Chem. 1997, 530,117.
[56] Stephanie Kmippel, Roland Frohlich, Gerhard Erker. Journal of Organometallic Chemistry, 1999, 586, 218-222.
[57]Cheikh M. N'Diaye, Lucien A. Maciejewski, Jacques S. Brocard and Christophe Biot. Tetrahedron letters, 2001,42, 7221-7223.
[58]P. Molina, A. Tarraga, D. Curiel, M. D. Velasco. Journal of Organometallic Chemistry, 2001, 637-639, 258-265.
[59]傅恩琴,王国超,薛鹏,高翠琴,吴成泰.化学通报, 1999,5,20-25.
[60] Patrick Liptau, Stephanie Knuppel, Gerald Kehr, Olga Kataeva, Roland Frohlich, Gerhard Erker. Journal of Organometallic Chemistry, 2001, 621-630.
[61] Andrew J. Locke and Chjristopher J. Richards. Organometallics, 1999,18,3750-3759.
[62]Andrew J. Locke, Claire Jones, and Chjristopher J. Richards. Journal of Organometallic Chemistry, 2001,637-639, 669-676.
[63]Bernd Wrackmeyer, Elena V. Klimkina and Wolfgang Milius. Inorganic Chemistry Communications, 2004,7,412-416.
[64]Toshiyuki Moriuchi, Seiji Bandoh, Yoko Miyaji, Toshikazu Hirao, Journal of Organometallic Chemistry, 2000,599,135-142.
[65]T. Moriuchi, I. Ikeda, Organometallics, 1995,14,3578.