研究生: |
葉耀廷 Yao-Ting, Yeh |
---|---|
論文名稱: |
掌性環亞基胺-N-氧化物化學: 多羥基吡咯和哌啶生物鹼的製備 Chiral Cyclic Nitrone Chemistry: Preparation of Polyhydroxylated Pyrrolidine and Piperidine Alkaloids |
指導教授: |
陳建添
Chen, Chien-Tien |
學位類別: |
碩士 Master |
系所名稱: |
化學系 Department of Chemistry |
論文出版年: | 2008 |
畢業學年度: | 96 |
語文別: | 中文 |
論文頁數: | 129 |
中文關鍵詞: | 多羥基吡咯 、多羥基哌啶 、醣水解酵素抑制劑 、環亞基胺-N-氧化物 |
英文關鍵詞: | Polyhydroxylated pyrrolidine, Polyhydroxylated piperidine, glycosidase inhibitors, Cyclic nitrone |
論文種類: | 學術論文 |
相關次數: | 點閱:134 下載:0 |
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多羥基吡咯和哌啶生物鹼的化合物結構吸引很多的化學合成家的注意,因其驚人的生物活性和具有作為藥物的的潛力,特別是在治療癌症、糖尿病和病毒的傳染病過程中作為醣水解酵素抑制劑。
因此發展新的方法合成多羥基吡咯和哌啶的化合物是相當的重要,尤其是此類環形結構的掌性衍生物。
在這論文中,我們利用D-木糖為起始物,發展新的合成方法,且有效率的合成多羥基吡咯和哌啶衍生物,以評估其生物活性。
The chiral polyhydroxy alkaloids have attracted considerable attention in organic synthesis owing to their remarkable biological properties and their potential as pharmaceuticals, especially, to serve as glycosidase inhibitors in treatment of cancers, diabetes and viral infections.
The development of new methods for the synthesis of pyrrolidine- or piperidine-based compounds is therefore of considerable importance, particularly for the approaches leading to chiral derivatives of these ring skeletons.
In this thesis, we have developed new and efficient synthetic protocols to prepare various polyhydroxylated pyrrolidine and piperidine-based alkaloids from D-xylose to evaluate their biological activities.
1. (a) Winchester, B.; Fleet, G. W. J. Glycobiology 1992, 2, 199-210. (b) Sears, P.; Wong, C. H. Angew. Chem. Int. Ed. 1999, 38, 2300-2324. (c) Wang, R. W.; Qing, F. L. Org. Lett. 2005, 7, 2189-2192.
2. (a) Butters. T. D.; Dwek, R. A.; Platt, F. M. Chem. Rev. 2000, 100, 4683-4696. (b) Watson, A. A.; Fleet, G. W. J.; Asano, N.; Molyneux, R. J.; Nash, R. J. Phytochem. 2001, 56, 265-295.
3. (a) Pinder, A. R. Nat. Prod. Rep. 1985, 2, 181-187. (b) Pinder, A. R. Nat. Prod. Rep. 1986, 3, 171-180. (c) Pinder, A. R. Nat. Prod. Rep. 1987, 4, 527-537. (d) Pinder, A. R. Nat. Prod. Rep. 1989, 6, 515-521. (e) Plunkett, A. O. Nat. Prod. Rep. 1994, 11, 581-590. (f) O’Hagan, D. Nat. Prod. Rep. 2000, 17, 435-446.
4. Inoue, S.; Tsuruoka, T.; Niida, T. J. Antibiot. 1966, 19, 288-292.
5. (a) Niwa, T.; Tsuruoka, T.; Goi, H.; Kodama, Y.; Itoh, J.; Inoue, S.; Yamada, Y.; Niida, T.; Nobe, M; Ogawa, Y. J. Antibiot. 1984, 37, 1579-1581. (b) Miyake, Y.; Ebata, M. Agric. Biol. Chem. 1988, 52, 661-666.
6. Inouye, S.; Tsurouka, T.; Ito, T.; Niida, T. Tetrahedron 1968, 24, 2125-2144.
7. Yagi, M.; Kouno, T.; Aoyagi, Y.; Murai, H. Nippon Nogei Kagaku Kaishi 1976, 50, 571-572.
8. Welter, A.; Jadot, J.; Dardenne, G.; Marlier, M.; Casimir, J. Phytochemistry 1976, 15, 747-749.
9. De Malo, E. B.; Gomes, A. D. S.; Carvalho, I. Tetrahedron 2006, 62, 10277-10302.
10. Pearson, M. S. M.; Mathé-Allainmat, M.; Fargeas, V.; Lebreton, J. Eur. J. Org. Chem. 2005, 2159-2191.
11. Asano, N.; Ishii, S., Kizu, H.; Ikeda, K.; Yasuda, K.; Kato, A., Martin; O. R.; Fan, J. Q. Eur. J. Biochem. 2000, 267, 4179-4186.
12. Asano, N. Current Topics in Medicinal Chemistry 2003, 3, 471-484.
13. Zou, W. Current Topics in Medicinal Chemistry 2005, 5, 1363-1391.
14. (a) Jones, D. W. C.; Nash, R. J.; Bell, E. A.; Williams, J. M. Tetrahedron Lett. 1985, 26, 3125–3126. (b) Fleet, G. W. J.; Nicholas, S. J.; Smith, P. W.; Evans, S. V.; Fellows, L. E.; Nash, R. J. Tetrahedron Lett. 1985, 26, 3127–3130. (c) Asano, N.; Ikeda, K.; Yu, L.; Kato, A.; Takebayashi, K.; Adachi, I.; Kato, I.; Ouchi, H.; Takahata, H.; Fleet, G. W. J. Tetrahedron: Asymmetry 2005, 16, 223-229.
15. Yu, C. Y.; Asano, N.; Ikeda, K.; Wang, M. X.; Butter, T. D.; Wormald, M. R.; Dwek, R. A.; Winters, A. L.; Nash, R. J.; Fleet, G. W. J. Chem. Commun. 2004, 1936-1937.
16. Zhou, X.; Liu, W. J.; Ye, J. L.; Huang, P. Q. Tetrahedron 2007, 63, 6346-6357.
17. Liu, J.; Shikhman, A. R.; Lotz, M. K.; Wong, C. H. Chem. Biol. 2001, 8, 701-711.
18. Wrodnigg, T. M.; Diness, F.; Gruber, C.; Hausler, H.; Lundt, I.; Rupitz, K.; Steiner, A. J.; Stütz, A. E.; Tarling, C. A.; Withers, S. G.; Wolfler, H. Bioorg. & Med. Chem. 2004, 12, 3485-3495.
19. Wrodnigg, T. M.; Stütz, A. E.; Withers, S. G. Tetrahedron Lett. 1997, 38, 5463-5466
20. Lie, J.; Numa, M. M. D.; Liu, H.; Huang, S. J.; Sears, P.; Shikhman, A. R.; Wong, C. H. J. Org. Chem. 2004, 69, 6273-6283.
21. Liang, P. H.; Cheng, W. C.; Lee, Y. L.; Yu, H. P.; Wu, Y. T.; Lin, Y. L.; Wong, C. H. ChemBioChem 2006, 7, 165-173.
22. Kilonda, A.; Compernolle, F.; Peeters, K.; Gert, J.; Toppet, S.; Hoornaert, G. Tetrahedron 2000, 56, 1005-1012.
23. McCort, I.; Fort, S.; Dureault, A.; Depezay, J. C. Bioorganic and Medicinal Chemistry, 2000, 8, 135-143.
24. Poupon, E.; Luong, B. X.; Chiaroni, A.; Kunesch, N.; Husson, H. P. J. Org. Chem. 2000, 65, 7208-7210.
25. (a) Cardona, F.; Goti, A. Angew. Chem. Int. Ed. 2005, 44, 7832-7835. (b) Koumbis, A. E.; Gallos, J. K. Current Organic Chemistry, 2003, 7, 585-628.
26. (a) Secrist Ⅲ, J. A.; Tiwari, K. N.; Shortnacy-Fowler, A. T.; Messini, L.; Riordan, J. M.; Montgomery, J. A. J. Med. Chem. 1998, 41, 3865-3871. (b) Behr, J. B.; Erard, A.; Guillerm, G. Eur. J. Org. Chem. 2002, 1256-1262.
27. (a) Barker, R.; Fletcher, H. G. J. Org. Chem. 1961, 26, 4605-4609. (b) Tejima, S.; Fletcher, H. G. J. Org. Chem. 1963, 28, 2999-3004.
28. Lucero, C. G.; Woerpel, K. A. J. Org. Chem. 2006, 71, 2641-2647.
29. Holzapfel, C. W.; Crous, R. Heterocycles 1998, 48, 1337-1342.
30. Yu, C. Y.; Huang, M. H. Org. Lett. 2006, 8, 3021-3024.
31. (a) Toyao, A.; Tamura, O.;Takagi, H.;Ishibadhi, H. Synlett 2002, 1, 35-38. (b) Desvergnes, S.; Py, S.; Vallée, Y. J. Org. Chem. 2005, 70, 1459-1462. (c) Carmona, A. T.; Whigtman, R. H.; Robina, I.; Vogel, P. Helvetica Chim. Acta 2003, 86, 3066-3073. (d) Cardona, F.; Faggi, E.; Liguori, F.; Cacciarini, M.; Goti, A. Tetrahedron Lett. 2003, 44, 2315-2318. (e) Gurjar, M. K. ; Borhade, R. G.; Puranik, V. G.; Ramana, C. V. Tetrahedron Lett. 2006, 47, 6979-6981.
32. (a) Goti, A.; Cicchi, S.; Mannucci, V.; Cardona, F.; Guarna, F.; Merino, P.; Tejero, T. Org. Lett. 2003, 5, 4235-4238. (b) Marradi, M.; Cicchi, S.; Delso, J. I.; Rosi, L.; Tejero, T.; Merino, P.; Goti, A. Tetrahedron Lett. 2005, 46, 1287-1290.
33. (a) Alcón, M.; Poch, M.; Moyano, A.; Pericàs, M. A.; Riera, A. Tetrahedron: Assymmetry 1997, 8, 2967-2974. (b) Masson, G.; Cividino, P.; Py, S.; Vallée, Y. Angew. Chem. Int. Ed. 2003, 42, 2265-2268.
34. Cicchi, S.; Goti, A.; Brandi, A. Synthesis 2007, 4, 485-504.
35. Tamura, O.; Toyao, A.; Ishibashi, H. Synlett 2002, 8, 1344-1346.
36. Stewart, A. O.; Martin, J. G. J. Org. Chem. 1989, 54, 1221-1223.
37. Pilcher, A. S.; Ammon, H. L.; DeShong, P. J. Am. Chem. Soc. 1995, 117, 5166-5167.