簡易檢索 / 詳目顯示

回結果列表
研究生： 吳啟誠
論文名稱： 利用 Vilsmeier-Haack 反應合成海洋生物鹼 isophakellin 及 ugibohlin 的 A-B-C 三環結構
Synthesis of the tricyclic A-B-C ring of marine alkaloids isophakellin and ugibohlin
指導教授： 簡敦誠
學位類別： 碩士
Master
系所名稱： 化學系
Department of Chemistry
論文出版年： 2011
畢業學年度： 99
語文別： 中文
論文頁數： 74
中文關鍵詞： 海洋生物鹼
英文關鍵詞： marine alkaloid
論文種類： 學術論文
相關次數： 點閱：60  下載：3 
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報

    • 天然界中有一系列的海洋生物鹼，包含isophakellin (1a) 、 ugibohlin (5b) 和其他結構類似物，它們具有pyrrole和imidazole的單元結構，並被證實含有抗腫瘤、抑制免疫的活性與顯著的低毒性，讓這些海洋生物鹼成為全合成的目標產物。我們主要的研究目標，為發展三環化合物4-amino-5,6,7,9-tetrahydropyrrolo[2,3-f]indolizin-9-one (3-10a~3-10d) 的合成途徑，做為isophakellin (1a) 和 ugibohlin (5b)的A-B-C三環並作為其全合成的前驅物。
    在海洋生物鹼A-B-C三環的合成研究中，我們利用pyrrole (3-1) 與trichloroacetyl chloride 行Friedel-Crafts reaction生成2-(trichloroacetyl)-1H-pyrrole (3-3)，再將其水解為pyrrole-2- carboxylic acid (3-6) 與一系列N-alkyl proline amides進行脫水反應合成含有A-C環的N-(1H-Pyrrole-2-carbonyl)-pyrrolidine-2-carboxylic acid amides (3-9a~3-9f) ，這些醯胺化合物經由Vilsmeier-Haack反應得到預期的A-B-C環化合物研究，我們的研究成果提供實用途徑來合成三環化合物(3-10a~3-10d)，並可作為 isophakellin (1a) 和 ugibohlin (5b) 全合成的前驅物。

    A series of marine natural products, including isophakellin (1a) and ugibohlin (5b), have been reported to conceive pyrrole and imidazole units. They have been revealed to contain effective antitumor activity, essential immunosuppressive activity and obvious low toxicity, which have enabled these alkaloids to become attractive targets for total syhthesis. Our specific aim was to establish a feasible synthesis for the tricyclic A-B-C ring of marine alkaloids, 4-amino-5,6,7,9- tetrahydropyrrolo[2,3-f]indolizin-9-one (3-10a-3-10d), as synthetic precursors for the total synthesis of isophakellin (1a) and ugibohlin (5b).
    In our synthesis of the tricyclic A-B-C ring of marine alkaloids, 2-(trichloroacetyl)-1H-pyrrole (3-3) as starting material was prepared from pyrrole (3-1) and trichloroacetyl chloride by Friedel-Crafts reaction. 2-(Trichloroacetyl)-1H-pyrrole (3-3) was hydrolyzed to pyrrole-2- carboxylic acid (3-6) and then coupled with a series of N- alkyl proline amides to afford N-(1H-pyrrole-2-carbonyl)-pyrrolidine-2-carboxylic acid amides (3-9a~3-9f), as the A-C ring units. These amides were subjected to the optimized Vilsmeier-Haack reaction condition and the desired tricyclic A-B-C ring of marine alkaloids such as isophakellin (1a) and ugibohlin (5b) were obtained in good yields The expedient synthesis of tricyclic ring compound (3-10a~3-10d) provide suitable precursors for the total synthesis of isophakellin (1a) and ugibohlin (5b).

    目錄............................................................................................................1 藥品試劑縮寫對照表................................................................................2 Abstract.....................................................................................................3 中文摘要....................................................................................................4 第一章 緒論..............................................................................................5 第二章 化學合成與方法 ........................................................................9 第三章 結果與討論................................................................................23 第四章 結論............................................................................................46 第五章 實驗步驟....................................................................................49 5.1 一般實驗處理...............................................................................49 5.2 儀器設備.......................................................................................49 5.3 實驗步驟.......................................................................................51 第六章 參考文獻....................................................................................72

    1. Al Mourabit, A.; Potier, P. Eur. J. Org. Chem. 2001, 237-243
    2. Hoffmann, H. ; Lindel, T. Synthesis, 2003, 12, 1753-1783
    3. Bickmeyer, U. ; Grube, A; Klings, K.-W.; Koeck, M. Toxicon 2007, 50, 490-497.
    4. Zoellinger, M.; Kelter, G.; Fiebig, H.-H.; Lindel, T. Bioorg. Med. Chem. Lett. 2007, 17, 346-349.
    5. Kato,T.; Shizuri, Y.; Izumida, H.; Yokoyama, A.; Endo, M. Tetrahedron Lett. 1955,36, 2133-2136.
    6. Kinnel, R. B.; Gehrken, H. P.; S cheuer, P. J. J. Am. Chem. Soc. 1933, 115,3376-3377.
    7. Kinnel, R. B.; Gehrken, H. P.; Swali, R.; Skoropowski, G.; Scheuer, P. J. J. Org. Chem. 1998, 63, 3281-3286.
    8. Denanteuil, G.; Ahond, A.; Guilhem, J.; Poupat, C.; Dau, E. T. H.; Potier, p.; Pusset, M.; Pusset, J.; Laboute, P. Tetrahedron 1985, 41, 6019-6033.
    9. Fedoreyev, S. A.; Utkina, N. K.; Ilyin, S. G,; Reshetnyak, M. V.; Maximov, O. B. Tetrahedron Lett. 1986, 27, 3177-3180.
    10. Assmann, M.; van Soest, R. W. M.; Kock, M. J. Nat. Prod. 2001, 64, 1345-1347.
    11. Sharma, G. M.; Burkohold, P. R. J. Chem. Soc. D, Chem. Commun. 1971, 151-152.
    12. Sharma, G.; Magdofffairchild, B. J. Org. Chem. 1977, 42, 4118-4214.
    13. Foley, L. H.; Buchi, G. J. Am. Chem. Soc. 1982, 104, 1776-1777.
    14. Wiese, K. J.; Yakushijin, K.; Horne, D. A. Tetrahedron Lett. 2002, 43, 5135-5136.
    15. Wang, S.; Romo, D. Angew. Chem. Int .Ed. 2008, 47, 1284-1286.
    16. Poullennec, K. G.; Romo, D. J. Am. Chem. Soc. 2003, 125,6344-6345.
    17. Chung, R.; Yu, E.; Incarvito, C.D.; Austin, D. J.Org. Lett. 2004, 6, 3881-3884.
    18. Zoellinger, M.; Mayer, P.; Lindel, T. Synlett 2007, 17, 2756-2758.
    19. Zoellinger, M.; Mayer, P.; Lindel, T. J. Org. Chem. 2006, 71, 9431-9439.
    20. Gaich, T.; Baran, P.S. J. Org. Chem. 2010, 75, 4657-4673.
    21. Lindel, T.; Hoffmann, H. Liebigs Ann. Chem. 1997, 1525-1528.
    22. Mizuni, A.; Inomata, N.; Miya, M.; Kamel, T.; Shibata, M.; Tatsuoka, T.; Yoshida, M.; Takiguchi, C.; Miyazaki, T. Chem. Pharm. Bull. 1999, 47, 246-256.
    23. Matoba, K.; Fukushima, A.; Takahata, H.; Hirai, Y.; Yamazaki, T. Chem. Pharm. Bull. 1982, 30, 1300-1306.
    24. Foley, L. H.; Buchi, G. J. Am. Chem. Soc. 1982.104,1776-1777.
    25. Sosa, A. C. B.; Yakushijin, K.; Horne, D. A. Tetrahedron Lett. 2000, 41, 4295-4299.
    26. Annoura, H.; Tatsuoka, T. Tetrahedron Lett.1995, 36, 413-416.
    27. Xu, Y. Z.; Phan, G.; Yakushijin, K.; Horne, D. A. Tetrahedron Lett. 1994, 35, 351-354.
    28. Marchais, S.; Al Mourabit, A.; Ahond, A.; Poupat, C.; Potier, P. Tetrahedron Lett. 1999, 40, 5519-5522.
    29. Wang, S.; Room, D. Angew. Chem. Int. Ed., 2008, 47, 1284-1286.
    30. Travert, N.; Martin, M., T.; Edron-Kondracki, M., L.; Al-Mourbit, A. Tetrahedron Lett. 2005, 46, 249-252.
    31. Jacquot, D., E., N.; Hoffmann, H.; Polborn, K.; Lindel, T. Tetrahedron Lett. 2002, 43, 3699-3702.
    32. Zollinger, M.; Mayer, P.; Lindel, T.J. Org. Chem., 2006, 71, 9431-9439.
    33. Jacquot, D., E., N.,; Zollinger, M.; Lindel,T. Angew. Chem. Int. Ed., 2005, 44, 2295-2298
    34. Chang Y. -Y., Study On Total Syntheseis Of A-B-C Ring For Marine Alkaloid (±)-Dibromoisophakellin; M. Sc. Thesis, National Taiwan Normal University, 2009.
    35. Schmuck, Carsten; Bickert, Volker; Merschky, Michael; Geiger, Lars; Rupprecht, Daniel; Dudaczek, Juergen; Wich, Peter; Rehm, Thomas; Machon, Uwe. Eur. J. Org. Chem. 2001, 237-243.
    36. Jacquot, D., E., N.,; Zollinger, M.; Lindel, T. Angew. Chem. Int. Ed., 2005, 44, 2295-2298.
    37. Jacquot, D., E., N.,; Hoffmann, H.; Polborn, K.; Lindel, T. Tetrahedron Lett. 2002, 43, 3699-3702.
    38. Xu, Y. Z.; Phan, G.; Yakushijin, K.; Horne, D. A. Tetrahedron Lett. 1994, 35, 351-354.
    39. Marchais, S.; Al Moruabit, A.; Ahond, A.; Poupat, C.; Potier, P. Tetrahedron Lett. 1999, 40, 5519-5522.
    40. R.-P. Moldovan, T. Lindel , Z. Naturforsch. B: Chem. Sci. 2009, 64b, 1612-1616.
    41. Chung, R.; Yu, E.; Incarvito, C., D.; Austin, D. J. Org. Lett. 2004, 6, 3881-3844.
    42. Lwowski, W.; Maricich, T. J. J. Am. Chem. Soc. 1965, 87, 3630-3637.

    下載圖示
    QR CODE