本篇論文主要分為兩個部份。第一部份主旨為 GFP 吸光基團類似物的合成研究。利用 N-acylglycine 為起始物，在醋酸鈉 / 醋酸酐的條件下與各種取代基的苯甲醛進行 Erlenmeyer azlactone synthesis 反應形成 4-arylidene-5-oxazolinone 衍生物。接下來再使用一級胺在室溫下對 oxazolinone 進行開環反應，可以得到含有直鏈結構的 N-alkyl-2-acylamido-3-arylacrylamide。接下來有兩個方法可以進行合環反應，一個是使用 pyridine 作為反應試劑和反應溶劑，進行脫水合環反應形成 4-arylidene-5-imidazolinone 衍生物，適用於不同官能基上；另外一個是使用改良後的 Mitsunobu 反應，一樣可以進行合環反應，雖然有些例子產率不高，但這是一個較為溫和的反應。
　　第二部份是合成 α-(pyrrol-2-yl)pyrrolidine 衍生物。使用氮上有 Bn 保護的 proline 當作起始物，與 thionyl chloride 反應得到醯氯的中間物，隨後使用鹼和 pyrrole 反應，得到α-(pyrrol-2-yl)pyrrolidine 衍生物。在本論文中，我們研究了本反應的適用性，並用來製備一系列α-(pyrrol-2-yl)pyrrolidine 衍生物。

This thesis is divided into two parts. The main focus of the first part is to study the synthesis of Green Fluorescent Protein (GFP) chromophore analogs. N-acylglycine as the starting material was heated with sodium acetate and various benzaldehydes in acetic anhydride to undergo the Erlenmeyer azlactone synthesis reaction to afford a series of 4-arylidene-5-oxazolinones. The oxazolinones were treated with primary amines to give the ring-opened adducts which contain the N-alkyl-2-acylamido-3-arylacrylamide moiety. We first demonstrated that, using pyridine as the reagent and solvent, the ring-opened adducts were heated in pyridine to undergo the dehydrative cyclization reaction to afford the ring-closed 4-arylidene-5-imidazolinone derivatives as the GFP chromophore analogs. Alternatively, our investigation also showed that a modified Mitsunobu reaction condition could also accomplish the same reaction to give the 4-arylidene-5-imidazolinone derivatives.
　　The second part reported a novel reaction for the synthesis of α-(pyrrol-2-yl)pyrrolidine derivatives. N-benzylproline as starting material was treated with thionyl chloride to afford the acyl chloride intermediate. Subsequently, pyrrole was added in the presence of a base to result a decarbonylated product which was identified as an α-(pyrrol-2-yl)pyrrolidine derivative. The scope and generality were examined and the reaction is applicable to a series of pyrrole derivatives.

1.Davenport, D.; Nicol, J. A. C., Proc. R. Soc. London, Ser. B 1955, 144, 399.
2.Shimomura, O.; Johnson, F. H.; Saiga, Y. J. Cell. Physiol. 1962, 59, 223.
3.Morin, J. G.; Hastings, J. W. J. Cell Physiol. 1971, 77, 313.
4.Morise, H.; Shimomura, O.; Johnson, F. H.; Winant, J. Biochemistry 1974, 13, 2656.
5.Wu, L.; Burgess, K., J. Am. Chem. Soc. 2008, 130, 4089.
6.Shimomura, O., FEBS Lett. 1979, 104, 220.
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.
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.
9.Erlenmeyer, J., Liebigs Ann. Chem. 1893, 275, 1.
10.Lin, H. C. Design and Synthesis of 1-Substituted 4-Benzylidene-2-
Methyl-5-imidazolinone Derivatives as GFP analogs; M.Sc. Thesis, National Taiwan Normal University, 2009.
11.Lee, C. Y. Design and Synthesis of 1,2-Substituted 4-Benzylidene-5-
Imidazolinone Derivatives as GFP Chromophore Analogs; M. Sc. Thesis, National Taiwan Normal University, 2010.
12.Chen, Y. C. Facile Synthesis of 4-Arylidene-5-imidazolinones as Synthetic Analogs of Fluorescent Protein Chromophore; M. Sc. Thesis, National Taiwan Normal University, 2011.
13.Arya, K. Synthesis 1985, 285.
14.Cativiela, C.; Chueca, J.; García, J. I.; Meléndez, E. Heterocycles 1984, 22, 2775.
15.Moxwa, E. B. J. Prakt. Chem. 1986, 295.
16.Bondock, S.; Khalifa, W.; Fadda, A. A. Synth. Commun. 2006, 36 (11), 1601.
17.Kojima, S.; Ohkawa, H.; Hirano, T.; Maki, S.; Niwa, H.; Ohashi, M.; Inouye, S.; Tsuji, F. I., Tetrahedron Lett. 1988, 39, 5239.
18.Kidwai, M.; Mohan, R. J. Chin. Chem. Soc. 2003, 50, 1075.
19.Topuzyan, V. O.; Oganesyan, A. A.; Panosyan, G.A., Russ. J. Org. Chem. 2004, 40, 1644.
20.Kawasaki, A.; Maekawa, K.; Kubo, K.; Igarashi, T.; Sakurai, T., Tetrahedron 2004, 60, 9517.
21.Yampolsky, I. V.; Remington, S.J.; Martynov, V.I.; Potapov, V. K.; Lukyanov, S.; Lukyanov, K.A., Biochemistry 2005, 44, 5788.
22.Rao, K. V. V. P.; Dandala, R.; Handa, V. K.; Rao, I. V. S.; Rani, A.; Shivashankar, S.; Naidu, A. Synlett. 2007, 1289.
23.Stafforst, T.; Diederichsen, U. Eur. J. Org. Chem. 2007, 899.
24.Petersen, M. A.; Riber, P.; Anderson, L. H.; Nielsen, M. B. Synthesis 2007, 3635.
25.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.
26.http://cbc.arizona.edu/njardarson/group/top-pharmaceuticalsposter.
27.Graeme, B.;Julia L.M.; Artis K.; Darren, S.; George, Z.; Kevin, R. C.; Peter O’Brien J. Org. Chem. 2011, 76, 5936.
28.Brennan, M. B. Chem. Eng. News 2000, 78 , 23.
29.Zhang, Q.; Tu, G.; Zhao, Y.; Cheng, T. Tetrahedron 2002, 58, 6795.
30.Kam, T. S.; Sim, K. M. Phytochemistry 1998, 47, 145.
31.David, S. G.; Wasicak, J. T.; Elliott, R. L.; Lebold, S. A.; Hettinger, A. M.; Carrera, G. M.; Lin, N. H.; He, Y.; Holladay, M. W.; Anderson, D. J.; Cadman, E. D.; Raskiewicz, J. L.; Sullivan, J. P.; Arneric, S. P. J. Med. Chem. 1994, 37, 4455.
32.Cosford, N. D. P.; Bleicher, L.; Herbaut, A.; McCallum, J. S.; Vernier, J. M.; Dawson, H.; Whitten, J. P.; Adams, P.; Chavez-Noriega, L.; Correa, L. D.; Crona, J. H.; Mahaffy, L. S.; Menzaghi, F.; Rao, T. S.; Reid, R.; Sacaan, A. I.; Santori, E.; Stauderman, K. A.; Whelan, K.; Lloyd, G. K.; McDonald, I. A. J. Med. Chem. 1996, 39, 3235.
33.Manfré, F.; Pulicani, J. P. Tetrahedron: Asymmetry 1994, 5, 235.
34.Kozmin, S. A.; Rawal, V. H. J. Am. Chem. Soc. 1997, 119, 7165.
35.Choi, Y. H.; Choi, J. Y.; Yang, H. Y.; Him, Y. H. Tetrahedron: Asymmetry 2002, 13, 801.
36.Reisman, S. E.; Doyle, A. G.; Jacobsen, E. N. J. Am. Chem. Soc. 2008, 130, 7198.
37.Peterson, E. A.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2009, 48, 6328.
38.Knowles, R. R.; Lin, S.; Jacobsen, E. N. J. Am. Chem. Soc. 2010, 132, 5030.
39.Higashiyama, K.; Inoue, H.; Takahashi, H. Tetrahedron 1994, 50, 1083.
40.Burgess, L. E.; Meyers, A. I. J. Org. Chem. 1992, 57, 1656.
41.Manescalchi, F.; Nardi, A. R.; Savoia, D. Tetrahedron Lett. 1994, 35, 2775.
42.Brinner, K. M.; Ellman, J. A. Org. Biomol. Chem. 2005, 3, 2109.
43.(a) Reddy, L. R.; Prashad, M. Chem. Commun. 2010, 222; (b) Reddy, L. R.; Das, S. G.; Liu, Y.; Prashad, M. J. Org. Chem. 2010, 75, 2236.
44.Leemans, E.; Mangelinckx, S.; De Kimpe, N. Chem. Commun. 2010, 3122.
45.Ozawa, F.; Hayashi, T. J. Organomet. Chem. 1992, 428, 267.
46.Willoughby, C. A.; Buchwald, S. L. J. Org. Chem. 1993, 58, 7627.
47.Wu, S.; Lee, S.; Beak, P. J. Am. Chem. Soc. 1996, 118, 715.
48.Rapoport, H.; Castagnoli, N. Jr. J. Am. Chem. Soc. 1962, 84, 2178.
49.Kiyooka, Syun-ichi; Sekimura, Yasuhito; Kawaguchi, Katsuhiko Synthesis 1988, 745.
50.Garvey, D. S.; Wasicak, J. T.; Chung, J. Y.-L.; Shue, Y. K.; Carrera, G. M.; May, P. D.; McKinney, M. M.; Anderson, D.; Cadman, E.; Vella-Rountree, L.; Nadzan, A. M.; Williams, M. J. Med. Chem. 1992, 35, 1550.
51.Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923.