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 |
相關次數: | 點閱:63 下載:0 |
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 |
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.
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.