臺灣博碩士論文加值系統

摘要
我們設計合成一系列具有triketone結構之潛在抑制劑，2-o-halobenzoyl-cyclohexane-1,3-diones 28-35及 2-alkylcarbonyl-cyclo-hexane-1,3-diones 36-39等化合物，利用烯醇硼酸鹽互變異構法測試其對對羥苯丙酮酸雙氧 (4-hydroxyphenylpyruvate diox-ygenase)之活性，均能有效抑制對羥苯丙酮酸雙氧之活性。其中最強之抑制劑為當2-benzoylcyclclohexane-1,3-diones上ortho位置取代基為-NO2，時IC50 值為0.16μM。
另外我們合成具有3-alkanyloxy-2-cyclohexen-1-one 結構之non-triketone之潛在抑制劑，如化合物47-59，均能有效抑制對羥苯丙酮酸雙氧之活性。化合物3-Cyclopropane carbonyloxy-2-(chloro)cycl-ohexen-1-one 56抑制能力最強，IC50值為0.015μM。

目錄
摘要………………………………………………………………Ⅰ
壹、緒論……………………………………………………………….1
貳、實驗設計(一)…………………………………………………….11
實驗設計(二)…………………………………………………….15
參﹑結果與討論
實驗(一)………………………………………………………….22
實驗(二)……………………………………………………….…26
肆、結論………………………………………………………………..29
伍、實驗
一、儀器設備及試藥來源……………………………………..31
二、酵素純化及分析
(一)苯丙酮酸互變異構的純化及分析……………….34
(二)對羥苯丙酮酸雙氧的純化……………………….36
(三)電泳………………………………………………….41
三、化合物的合成…………………………………………….44
(一)分析原理…………………………………………….63
(二)分析程序…………………………………………….64
(三) 抑制結果…………………………………………..65
陸、參考資料…………………………………………………………..83
柒、光譜資料…………………………………………………………..86

參考文獻
1. Bender, D. A. (1985) in "Amino Acid Metabolism",2nd ed, p212,
John Wiley & Sons. London.
2. Ministry of Health, Mortality and Morbidity during the London fog of December 1952. London: HM sationery Officer, 1954.
3. Scheparts, B.; Gurin, S. J. Biol. Chem. 1949, 180, 663.
4. Lindstedt, S,; Holme, E.; Lock, E,; Hjalmarson, O,; Strandvik, B. Lancet 1992, 340, 813.
5. Therfall, D. R. Biochim. Biophys. Acta 1972, 280, 472.
6. Lindblad, B.; Lindstedt, G.; Lindstedt, S.; Rundgren, M. J. Biol.
Chem. 1977, 252, 5073.
7. Roche, P. A.; Moorehead, T. J.; Hamolton, G. A. Arch. Biochem. Biophys. 1982, 26, 62
8. Laskowska-Klita, T.; Mochnacka, I. Acta. Biochim. Pol. 1973, 20, 259.
9. Nakai, C.; Nozaki, M.; Hayaishi, O.; Saito, I.; Matsuura, T. Biochem. Biophys. Res. Commun. 1975, 67, 590.
10. Lin, K.; Crawhill, J. C. Can. J. Biochem. 1976, 54, 423.
11. Wada, G. H.; Fellman, J. H. Methods Enzymol. 1987, 142, 148.
12. Lindstedt, S.; Odelhog, B.; Rundgren, M. Biochemistry 1977, 16, 3369.
13. Endo, F.; Awata,H.; Tanoue, A.; Ishiguro, M.; Eda, Y.; Titani, K.; Matsuda, I. J. Biol. Chem. 1992, 267, 24235.
14. Lindblad, B.; Lindstedt, G.; Lindstedt, S. J. Am. Chem. Soc. 1970, 92, 7446.
15. Rundgren, M. J. Biol. Chem. 1977, 252, 5094.
16. Leinberger, R.; Hull, W. E.; Simon, H.; Retey,J. Eur. J. Biochem. 1981, 117, 311.
17. Goodwin, s.; witkop, b. J. Am. Chem. Soc. 1957, 79, 179.
18. Hamilton, G. A. Bioorg. Chem. 1971, 1, 83.
19. Nicholas, P. Chouch.; Robert, M. Adlington.; Jack, E. Baldwin.
Tetrahedron. 1997, 53, 6993.
20. Patrick ,J. Sabourin.; Loran, L. Bieber. Biological Chemistry. 1982, 257,7468.
21. Lindstedt, S.; Holme, E.; Lock, E.A. Lancet 1992, 340,813.
22. Ellis, M. K.; Whitfielf, A. C. W.; Smith, L. L. Toxicology And Applied Pharmacology 1995, 133, 12.
23. Lee, D. L.; Prisbylla, M. P; Cromartie, T. H.; Dagarin, D. P.;
Howard, S. W.; Provan, W. M.; Ellis, M. K.; Fraser, T.; Mutter,
L. C. Weed Sci. 1997, 45,601.
24. Michaely, W. J,; Kratz, G. W. USPatent NO. 4,780,127, 1988.
25. Jacob, Secor. Plant Physiol, 1994, 106, 1429.
26. (a).Burton, J. D.; Gronwaid, J. W.; Somers, D. A.; Gengenbach, B. G,; Wyse, D. L.; Connelly, J. A. Biophys. Res. Commun. 1987, 148, 1039. (b).Focke, M.; Lichtenthaler, H. K. Z. Naturforsch. 1987, 42c, 1361.
(c).Rendina, A. R.; Felts, J. M. Plant Physiol. 1988, 86, 983.
27. For recent reviews on the inhibition of ACCase by cyclohexanedione
Derivatives (a). Harwood, J. L. Trends Biochem. Sci. 1988, 13, 330.
(b). Knowles, J. R.. Ann. Rev. Biochem. 1989, 58, 195. (c). Gronwald, J. W. Biochem. Soc. Trans. 1994, 22, 616. (d). Herbert, D,; Walker, K. A.;Price, L. J.; Cole, D. J.; Pallett, K. E.; Ridley, S. M.; Harwood, J. L. Pestic. Sci. 1997, 148, 1039.
28. Lin,S-w.; Yang,D-y. Bioorg.Med.Chem.lett.1999, 9, 551.
29. (a). Buhler, D. D.; Swisher, B. A.; Burnside, O.C. Weed Sci. 1985, 33, 291. (b). Swisher, B. A.; Corbin, F. T. Weed Sci. 1982, 30, 640. (C). Ishikawa, H.; Yamada, S.; Hosaka, H.; Kawana, T.; Okunaki, J. S.; Kohara, K. J. Pestic. Sci. 1985, 10,187.
30. For a recent review see: Incledon, B. J.; Hall, J. C. Pest Biochem. Physiol. 1997, 57, 255.
31. Chem.Abs. 1992, 96, 1991 68w.
32. Robert, L.; William, E. H.; Helmut, S.; Janos, R. Eun. J. Biochem. 1981, 117, 311.
33. David, J. B.; Patrick, A. R.; Thomas, J. M.; Brian, J. R. F.; Gorgon, A. H. Methods in Enzymology. 1987, 142, 132.
34. Robing, G. S.; Alan, C. W.; Chem. Soc. Perkin Tran.Ⅰ. 1987, 2153.
35. James, L. C.; Howard, J. W.; Saukaran, N. J. Org. Chem. 1977, 42, 14.
36. Arakawa . Pharm. Bull. 1957, 5, 528.
37. Kopka, I.; Rathke, M. W.; J. Org. Chem. 1981, 46, 3771.