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研究生: 李承祐
論文名稱: 設計與合成 1,2-取代 4-Benzylidene-5-imidazolinone 衍生物作為 GFP Chromophore 類似物
Design and Synthesis of 1,2-Substituted 4-Benzylidene-5-imidazolinone Derivatives as GFP Chromophore Analogs
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: 2010
畢業學年度: 98
語文別: 中文
論文頁數: 217
中文關鍵詞: 螢光蛋白質
英文關鍵詞: GFP
論文種類: 學術論文
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  • 本論文主旨為 GFP chromophore 類似物的合成研究。利用 N-acylglycine 為起始物,在醋酸酐 / 醋酸鈉的條件下與各種具取代基的苯甲醛進行合環反應形成 4-benzylidene-5-oxazolinone的衍生物。我們先利用一級胺類或 C-端具保護基的胺基酸於室溫下對oxazolinone 進行開環,形成含有 2-acylamido-3-arylacrylamide 的直鏈開環結構,再利用本論文的條件,以 pyridine 為溶劑和反應試劑,對其進行合環反應,有效率的形成一系列 4-benzylidene-5-imidazolinone的衍生物,之後並藉由方法學來測試此合環條件的普遍應用性。當使用不同的 N-acylglycines, 一級胺與各種苯環對位具取代基的苯甲醛,可以合成一系列的 1,2-位取代 4-benzylidene-5-imidazolinones 的衍生物作為 GFP chromophore 的類似物,包含了 1 位接有 CH3, Bn, CH2COOMe, CH2COOH, CH3CHCOOH, CH3CHCOOMe, H 的官能基;2 位接有 CH3, 2-phthalimidopropyl 的官能基;benzylidene對位上接有 H, halide, CN, OH 等的官能基。結果顯示,我們發展的方法經由開環再合環的路徑形成 4-benzylidene-5-imidazolinones,相較於之前文獻報導過的方法,更有效率且溫和。

    The main focus of this thesis is to study the synthesis of GFP chromophore analogs via a cyclization reaction. N-acylglycines were heated with various benzaldehydes and sodium acetate in acetic anhydride to form a series of 4-benzylidene-5-oxazolinone derivatives. The oxazolinones were treated with primary amines or C-terminal protected amino acids under room temperature to afford the ring-opened adducts, which contained the 2-acylamido-3-arylacrylamide moiety. Our investigation has found that the desired 4-benzylidene-5-imidazolinone derivatives could be obtained in good yields when the ring-opened adducts were heated in pyridine. We have also demonstrated the generality of the methodology. When different N-acylglycines and primary amines were employed, a wide variety of 1- and 2-substituted 4-benzylidene-5-imidazolinones could be obtained. It is also applicable to various para-substituted benzaldehydes that would afford different substituents at the para-position of the benzylidene.

    We have successfully synthesized a series of 1,2-substituted-4-benzylidene-5-imidazolinone as the analogs of GFP chromophores, comprising CH3, Bn, CH2COOMe, CH2COOH, CH3CHCOOH, CH3CHCOOMe, H at 1-position; CH3, Ph, 2-phthalimidopropyl at 2-position; H, halide, CN, OH at the para-position of benzylidene. Our results have shown that our approach toward the 4-benzylidene-5-imidazolinones from ring-opening / ring-closing route is more facile and efficient than the existing methods.

    目錄 3 藥品試劑縮寫對照表 5 Abstract 6 中文摘要 7 第一章 緒論 8 第二章 GFP chromophore 類似物的合環探討與方法及延伸 11 2.1 序論 & 化學方法及合成 11 2.2 結果和討論 24 2.3 MIO 於化學方法合成之研究與探討 34 2.4 利用簡單化學方法作為延伸合成 GFP chromophore 類似物 39 2.5 設計與合成1-位取代4-benzylidene-2-methyl-5-imidazolinone衍生物作為GFP chromophore 類似物 40 第三章 設計與合成1,2-取代 4-benzylidene-5-imidazolinone 衍生物作為 GFP chromophore 類似物 44 第四章 結論 63 第五章 儀器設備、實驗步驟、參考文獻和光譜數據 65 5.1 一般實驗處理 65 5.2 儀器設備 65 5.3 實驗步驟 67 5.4 參考文獻 102 附圖 105 (光譜檔) 105

    1. Davenport, D.; Nicol, J. A. C., Proc. R. Soc. London, Ser. B 1955, 144, 399-411.
    2. Shimomura, O.; Johnson, F. H.; Saiga, Y., J. Cell. Physiol. 1962, 59, 223-229.
    3. Morin, J. G.; Hastings, J. W., J. Cell. Physiol. 1971, 77, 313-318.
    4. Morise, H.; Shimomura, O.; Johnson, F. H.; Winant, J., Biochemistry 1974, 13, 2656-2662.
    5. Wu, L.; Burgess, K., J. Am. Chem. Soc. 2008, 130, 4089-4096.
    6. Shimomura, O., FEBS Lett. 1979, 104, 220-222.
    7. Matz, M. V.; Fradkov, A. F.; Labas, Y. A.; Savitisky, A. P.; Zaraisky, A. G.; Markelov, M. L.; Lukyanov, S. A., Nat. Biotechnol. 1999, 17, 969-973.
    8. Terskikh, A.; Fradkov, A.; Ermakova, G.; Zaraisky, A.; Tan, P.; Kajava, A. V.; Zhao, X.; Lukyanov, S.; Matz, M.; Kim, S.; Weissman, I.; Siebert, P., Science 2000, 290, 1585-1588.
    9. Erlenmeyer, J., Liebigs Ann. Chem. 1893, 275, 1-8.
    10. Pinto, I. L.; West, A.; Debouck, C. M.; DiLella, A. G.; Gorniak, J. G.; O'Donnell, K. C.; O'Shannessy, D. J.; Patel, A.; Jarvest, R. L., Bioorg. Med. Chem. Lett. 1996, 6, 2467-2472.
    11. Yampolsky, I. V.; Kislukhin, A. A.; Amatov, T. T.; Shcherbo, D.; Potapov, V. K.; Lukyanov, S.; Lukyanov, K. A., Bioorg. Chem. 2008, 36, 96-104.
    12. Kojima, S.; Ohkawa, H.; Hirano, T.; Maki, S.; Niwa, H.; Ohashi, M.; Inouye, S.; Tsuji, F. I., Tetrahedron Lett. 1998, 39, 5239-5242.
    13. Arya., K., Synthesis 1985, 285-288.
    14. Cativiela, C.; Chueca, J.; García, J. I.; Meléndez, E., Heterocycles 1984, 22, 2775-2781.
    15. Moxwa, E. B., J. Prakt. Chem. 1986, 295-300.
    16. Kidwai, M.; Mohan, R., J. Chin. Chem. Soc. 2003, 50, 1075-1078.
    17. R'etey, J. a., Biochim. Biophys. Acta 2003, 1647, 179-184.
    18. Topuzyan, V. O.; Oganesyan, A. A.; Panosyan, G. A., Russ. J. Org. Chem. 2004, 40, 1644-1646.
    19. Kawasaki, A.; Maekawa, K.; Kubo, K.; Igarashi, T.; Sakurai, T., Tetrahedron 2004, 60, 9517-9524.
    20. Yampolsky, I. V.; Remington, S. J.; Martynov, V. I.; Potapov, V. K.; Lukyanov, S.; Lukyanov, K. A., Biochemistry 2005, 44, 5788-5793.
    21. Rao, K. V. V. P.; Dandala, R.; Handa, V. K.; Rao, I. V. S.; Rani, A.; Shivashankar, S.; Naidu, A., Synlett. 2007, 1289-1293.
    22. Stafforst, T.; Diederichsen, U., Eur. J. Org. Chem. 2007, 6, 899-911.
    23. Petersen, M. A.; Riber, P.; Andersen, L. H.; Nielsen, M. B., Synthesis 2007, 3635-3638.
    24. Hassanein, H. H.; Maha, M. K.; EI-Samaloty, O. N.; EI-Rahim, M. A.; Taha, R. A.; Magda, M. F. I., Arch. Pharmacal Res. 2008, 31, 562-568.
    25. Jursic, B. S.; Sagiraju, S.; Ancalade, D. K.; Clark, T.; Stevens, E. D., Synth. Commun. 2007, 37, 1709 - 1714.
    26. Poppe, L.; Rétey, J., Angew. Chem. Int. Ed. 2005, 44, 3668-3688.
    27. Martin Langer, A. P.; J'anos, R., Angew. Chem. Int. Ed. 1995, 34, 1464-1465.
    28. Poppe, L., Curr. Opin. Chem. Biol. 2001, 5, 512-524.
    29. János, R., Biochim. Biophys. Acta (BBA) - Proteins & Proteomics 2003, 1647, 179-184.
    30. Barondeau, D. P.; Kassmann, C. J.; Tainer, J. A.; Getzoff, E. D., Biochemistry 2005, 44, 1960-1970.
    31. Barondeau, D. P.; Kassmann, C. J.; Tainer, J. A.; Getzoff, E. D., J. Am. Chem. Soc. 2007, 129, 3118-3126.
    32. Sibi, M. P.; Marvin, M.; Sharma, R., J. Org. Chem. 1995, 60, 5016-5023.
    33. Liotta, D.; Sunay, U.; Santiesteban, H.; Markiewicz, W., J. Org. Chem. 1981, 46, 2605-2610.
    34. Bose, A. K.; Greer, F.; Price, C. C., J. Org. Chem. 1958, 23, 1335-1338.
    35. Shin, Chung-gi; Yonezawa, Y.; Yamada, T., Chem. Pharm. Bull. 1984, 32, 3934-3944.
    36. Dong, J.; Abulwerdi, F.; Baldridge, A.; Kowalik, J.; Solntsev, K. M.; Tolbert, L. M., J. Am. Chem. Soc. 2008, 130, 14096-14098.
    37. Bet, B.; lstrok; akowska; Banecki, B.; Czaplewski, C. L.; ankiewicz; Wiczk, W., Int. J. Chem. Kinet. 2002, 34, 148-155.
    38. Hiroyuki, M.; Yoshio, N., Chem. Pharm. Bull. 2002, 50, 1137-1140.
    39. Conley, J. D.; Kohn, H., J. Med. Chem. 1987, 30, 567-574.
    40. Sandhu, S. S.; Singh, J.; Sharma, S., J. Indian Chem. Soc. 1989, 66, 104-105.
    41. Yennu, S. L.; Divi, S. I., J. Chem. Soc., Perkin Trans. 1 1995, 3043 - 3045.
    42. Crawford; Little, J. Chem. Soc. 1959, 729.
    43. Poisel, H., Chem. Ber. 1977, 110, 948-953.
    44. Johnson; Nicolet, J. Am. Chem. Soc. 1912, 34, 1048-1054.
    45. Paula, M. T.; Ferreira, H. L. S.; Maia, L. S.; Monteiro; Joana S., J. Chem. Soc., Perkin Trans. 1 2001, 3167–3173.
    46. Jakubke, H. D., Chem. Ber. 1964, 97, 2816 - 2828.
    47. Yamashita; Yashiro, Nippon Nogei Kagaku Kaishi 1954, 28, 674.
    48. Mitsunobu, O.; Yamada, M.; Mukaiyama, T., Bull. Chem. Soc. Jpn. 1967, 40, 935-939.
    49. Jye-ShaneYang; Guan-Jhih Huang; Yi-Hung Liu; Shie-Ming Peng, Chem. Commun. 2008, 1344–1346.
    50. Wei-Ti Chuang; Bo-So Chen; Kew-Yu Chen; Cheng-Chih Hsieh; Pi-Tai Chou, Chem. Commun. 2009, 6982–6984.

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