簡易檢索 / 詳目顯示

回結果列表
研究生： 郭俊偉
Chun-Wei Kuo
論文名稱： 壹、N-溴代丁二醯亞胺作為催化劑在有機合成上的應用; 貳、磷化物在有機合成上之應用；參、合成含有1,2,4-噁二唑之吡唑類衍生物在CB1受體拮抗劑之生物活性研究
(I) Novel synthetic strategy for the synthesis of biologically active N-heterocycles catalyted by N-bromosuccinimide (II) Application of phosphous reagent in organic synthesis (III) SAR study on novel series of oxadiazoles as CB1 cannabinoid receptor antagonists
指導教授： 姚清發
Yao, Ching-Fa
夏克山
Shia, Kak-Shan
學位類別： 博士
Doctor
系所名稱： 化學系
Department of Chemistry
論文出版年： 2008
畢業學年度： 96
語文別： 中文
論文頁數： 370
中文關鍵詞： N-溴代丁二醯亞胺 、催化劑 、磷化物 、1,2,4-噁二唑 、吡唑 、CB1受體拮抗劑
英文關鍵詞： N-bromosuccinimide, catalyst, phosphorus reagent, 1,2,4-oxadiazole, pyrazole, CB1 receptor antagonist
論文種類： 學術論文
相關次數： 點閱：213  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

    • 本論文共分成三部分
    第一部分以便宜易取得之N-溴代丁二醯亞胺 (NBS) 試劑，分別催化合成具生物活性1,5-benzodiazepines衍生物以及吲哚基硝基烷化合物，此高效催化效率皆可使反應順利進行，並得到高產率的產物。
    第二部分以磷化物試劑，二氯化磷酸乙酯 (ethyl dichlorophosphate)或是二氯化磷酸苯酯 (phenyl dichlorophosphate)進行官能基的轉變及Beckmann 重排反應，反應順利可在室溫下進行並且得到高產率的產物。
    第三部分為探討含1,2,4-噁二唑為新型CB1受體拮抗劑之抗肥胖藥物的開發研究，以Rimonabant（SR141716A, Acomplia™）作為先導化合物進行pyrazole-C3位置的官能基修飾，依生物同質性概念成功引入1,2,4-噁二唑取代之新型化合物並顯現高度之CB1受體親和力、功能活性與CB2/1選擇性。發現具高度CB1親和力與CB2/1選擇性的化合物如11g, 11h等，將適合針對減重機制與抗肥胖藥物的特性進一步深入研究動物體內活性（in vivo efficacy）、藥物動力學（pharmacokinetics）及毒理試驗（toxicology）期能獲得具有潛力治療肥胖症的先導藥物或候選藥物。

    In the first part of this dissertation, we have focused on the use of relatively low toxic, inexpensive reagents such as N-bromosuccinimide for carrying out the catalytic synthetic methodology. Various biologically important 1,5-benzodiazepine derivatives were efficiently synthesized in excellent yields. Furthermore, 3-indolyl-nitroalkane derivatives can be synthesized utilizing this newly development catalytic system as well.

    The second part is focused on ethyl dichlorophosphate mediates functional group transormation from primary amides into nitriles under mild condition. However, phenyl dichlorophosphate also promotes Beckmann rearrangement at room temperature with highly efficiently to afford products in good to high yields.

    Finally, a novel series of 1,2,4-oxadiazole as potent and selective CB1 cannabinoid receptor antagonists has been developed. Replacing the conventional pyrazole 3-aryl substituent of rimonabant with the 1,2,4-oxadiazole moiety, a novel class of 1,2,4-oxadiazole-pyrazole derivatives, behaving as highly potent CB1 receptor antagonists with good CB2/1 selectivity, was discovered.

    目 錄 中文摘要……………………………………………………………I 英文摘要……………………………………………………………II 縮寫對照表........................................III 第一章 N-溴代丁二醯亞胺作為催化劑在有機合成上的應用………1 1 緒論……………………………………………………………………1 1.1 NBS作為催化劑………………………………………………1 1.2 NBS作為氧化劑………………………………………………4 1.3 NBS在綠色化學的應用………………………………………7 1.4 NBS對酮的羰基鄰位氫取代的研究…………………………9 第一節 N-溴代丁二醯亞胺催化合成1,5-benzodiazepines衍生物…11 1 前言…………………………………………………………………11 1.1 合成1,5-benzodiazepines衍生物的方法……………………13 1.2 研究構想……………………………………………………20 1.3 實驗結果與討論……………………………………………21 1.4 結論……………..……………………………………………29 第二節 N-溴代丁二醯亞胺催化合成β-吲哚硝基烷化合物………31 1 前言…………………………………………………………………31 1.1 共軛硝基化合物……………………………………………….32 1.2 吲哚基硝基烷化合物的合成研究構想……………………34 1.3 實驗結果與討論……………………………………………37 1.3.1 共軛硝基苯乙烯衍生物的製備……………………………37 1.3.2 N-溴代丁二醯亞胺催化吲哚與共軛硝基苯乙烯衍生物的反 應…………………………………………………………37 1.4 結論……………………………………………………………46 第二章 磷化物在有機合成上之應用……………………………48 1 緒論…………..……………………………………………………48 1.1 磷化物試劑應用於有機合成之文獻介紹………………… 49 1.2 研究構想……………………………………………………55 1.3 實驗結果與討論………………………………………………55 1.4 結論……………………………………………………………61 第一節 磷化物試劑應用在Beckmann 重排反應之研究…………62 1 緒論…………………………………………………………………62 1.1氣、液相Beckmann 重排中的催化劑………………………63 1.1.1酸性試劑用於Beckmann 重排反應的研究……………64 1.2 離子液體用於Beckmann 重排反應的研究………………69 1.3 磷化物試劑用於Beckmann 重排反應的研究………………72 1.4 實驗結果與討論……………………………………………74 1.5 結論…………………………………………………………83 第三章 合成含有1,2,4-噁二唑之吡唑類衍生物在CB1受體拮抗劑之生物活性研究…………………………………………………………84 1 前言………………………………………………………………84 1.1 肥胖症（obesity）………………………………………84 1.2 抗肥胖藥物的分類…………………………………………88 1.2.1 抑制食慾的藥物（Anorexic drugs）…………………88 1.2.2 阻礙營養素吸收的藥物………………………………91 1.2.3 增加熱量消耗的藥物…………………………………92 1.3 類大麻素受體拮抗劑的抗肥胖藥物………………………93 1.3.1 內生性類大麻素系統（endogenous cannabinoids）…93 1.3.2 以CB1受體為標靶的抗肥胖藥物..............96 1.4 研究構想…………………………………………………101 2 結果與討論………………………………………………………103 2.1 oxadiazole衍生物之合成…………………………………103 2.2 生物活性評估與討論 ………………………………108 3 結論………………………………………………………………111

    1. Djerassi, C. Chem. Rev. 1948, 43, 271.
    2. Muller, T. E.; Beller, M. Chem. Rev. 1998, 98, 675.
    3. Talluri, S. K.; Sudalai, A. Org. Lett. 2005, 7, 855.
    4. Karimi, B.; Seradj, H. Synlett 2001, 519.
    5. Sun, X. F.; Sun, R. C.; Zhao, L.; Sun, J. X. J. Appl. Polym. Sci. 2004, 92, 53.
    6. Sun, X. F.; Sun, R. C.; Tomkinson, J.; Baird, M. S. Carbohydr. Polym. 2003, 53, 483.
    7. Sun, X. F.; Sun, R. C.; Sun, J. X. J. Mater. Sci. 2003, 38, 3915.
    8. Thakur, V. V.; Sudalai, A. Tetrahedron Lett. 2003, 44, 989.
    9. Khazaei, A.; Rostami, A.; Raiatzadeh, A.; Mahboubifar, M. Can. J. Chem. 2007, 85, 336.
    10. Sharma, V. B.; Jain, S. L.; Sain, B. J. Mol. Catal. 2005, 227, 47.
    11. Surendra, K.; Krishnaveni, N. S.; Rao, K. R. Tetrahedron Lett. 2005, 46, 4111.
    12. Reddy, M. S.; Narender, M.; Rao, K. R. Tetrahedron Lett. 2005, 46, 1299.
    13. Surendra, K.; Krishnaveni, N. S.; Kumar, V. P.; Sridhar, R.; Rao, K. R. Tetrahedron Lett. 2005, 46, 4581.
    14. Krishnaveni, N. S.; Surendra, K.; Rao, K. R. Adv. Synth. Catal. 2004, 346, 346.
    15. Kim, D. W.; Choi, H. Y.; Lee, K. J.; Chi, D. Y. Org. Lett. 2001, 3, 445.
    16. Rahman, A. N. M.; Bishop, R.; Tan, R.; Shan, N. Green Chem. 2005, 7, 207.
    17. Sarma, J. A. R. P.; Nagaraju, A. J. Chem. Soc., Perkin Trans. 2 2000, 1113.
    18. Sarma, J. A. R. P.; nagaraju, A.; Majumdar, K. K.; Samuel, P. M.; Das, I.; Roy, S.; McGhie, A. J. J. Chem.. Soc., Perkin Trans. 2 2000, 1119.
    19. Amijs, C. H. M.; Klink, G. P. M.; Koten, K. G. Green Chem. 2003, 5, 470.
    20. Rothenberg, G.; Downie, A. P.; Raston, C. L.; Scot, J. L. J. Am. Chem. Soc. 2001, 123, 8701.
    21. Yang, D.; Yan, Y. L.; Lui, B. J. Org. Chem. 2002, 67, 7429.
    22. Das, B.; Venkateswarlu, K.; Mahender, G.; Mahender, I. Tetrahedron Lett. 2005, 46, 3041.
    23. Tanemura, K.; Suzuki, T.; Nishida, Y.; Satsumabayashi, K.; Horaguchi, T. Chem. Commun. 2004, 470.
    24. (a) Schutz, H. Benzodiazepines; Springer: Heidelberg, 1982, (b) Landquist, J. K. In Comprehensive Heterocyclic Chemistry, Vol. 1; Katritzky, A. R.; Rees, C. W. Eds.; Pergamon: Oxford, 1984, 166-170, (c) Fryer, R. I. Bicyclic Diazapines, In The Chemistry of Heterocyclic Compounds, Vol. 50; Taylor, E. C., Eds.; Wiley: New York, 1991, Chap. II, (d) Randall, L. O.; Kappel, B. Benzodiazepines; Garattini, S.; Mussini, E.; Randall, L. O., Eds; Raven Press: New York, 1973, 27.
    25. De Baun, J. R.; Pallos, F. M.; Baker, D. R. U. S. Patent 3978227, 1976; Chem. Abstr. 1977, 86, 5498d.
    26. Haris, R. C.; Straley J. M. U. S. Patent 1537757, 1968; Chem. Abstr. 1970, 73, 100054w.
    27. (a) Aversa, M. C.; Ferlazzo, A.; Gionnetto, P.; Kohnke, F. H.; Synthesis 1986, 230, (b) Essaber, M.; Baouid, A.; Hasnaoui, A.; Benharref, A.; Lavergne, J. P. Synth. Commun. 1998, 28, 4097, (c) El-Sayed, A. M.; Abdel-Ghany, H.; El-Saghier, A. M. M. Synth. Commun. 1999, 29, 3561, (d) Chimirri, A.; Grasso, S.; Ottana, R.; Romeo, G.; Zappala, M. J. Heterocycl. Chem. 1990, 27, 371.
    28. Stahlhofen, P.; Ried, W. Chem. Ber. 1957, 90, 815.
    29. Ried, W.; Torinus, E. Chem. Ber. 1959, 92, 2902.
    30. (a) Balakrishna, M. S.; Kaboudin, B. Tetrahedron Lett. 2001, 42, 1127, (b) Curini, M.; Epifano, F.; Marcotullio, M. C.; Rosati, O. Tetrahedron Lett. 2001, 42, 3197, (c) Sabita, G.; Reddy. G. S. K.; Reddy, K. B.; Reddy, N. M.; Yadav, J. S. Adv. Synth. Catal. 2004, 346, 921, (d) Kaboudin, B.; Navaee, K. Heterocycles 2001, 55, 1443, (e) Pozarentzi, M.; Stephanatou, J. S.; Tsoleridis, C. A. Tetrahedron Lett. 2002, 43, 1755, (f) Reddy, B. M.; Sreekant, P. M. Tetrahedron Lett. 2003, 44, 4447, (g) Yadav, J. S.; Reddy, B. V. S.; Eshwaraiah, B.; Auradha, K. Green Chem. 2002, 4, 592, (h) Jarikote, D.V.; Siddiqui, S. A.; Rajagopal, R.; Daniel, T.; Lahoti, R. J.; Srinivasan, K. V. Tetrahedron Lett. 2003, 44, 1835, (i) Surya, K. De.; Gibbs, R. A. Tetrahedron Lett. 2005, 46, 1811.
    31. (a) Yadav, J. S.; Reddy, B. V. S.; Praveenkumar, S.; Nagaiah, K. Synthesis 2005, 480, (b) Das, B.; Ramu, R.; Ravikanth, B.; Reddy, V. S. J. Mol. Catal. A: Chem. 2006, 246, 76, (c) Thakuria, H.; Pramanik, A.; Borah, B. M.; Das, G. Tetrahedron Lett. 2006, 47, 3135, (d) Varala, R.; Enugala, R.; Nuvula, S.; Adapa, S. R. Synlett. 2006, 1009, (e) Kumar, R.; Chaudhary, P.; Nimesh, S.; Verma, A. K.; Chandra, R. Green Chem. 2006, 8, 519.
    32. P. I. Dalko and L. Moisan, Angew. Chem., Int. Ed. 2004, 43, 5138.
    33. (a) More, S. V.; Sastry, M. N. V.; Yao, C-F. Green Chem. 2006, 8, 91, (b) Ko, S.; Yao, C-F. Tetrahedron 2006, 62, 7293.
    34. (a) Sundberg, R. J. The Chemistry of Indoles; Academic: New York, 1996; p 113. (b) Livingstone, R. In Ansell, M. F., Ed.; Rodd’s Chemistry of Carbon Compounds; Elsevier: Oxford, 1984; Vol. 4.
    35. Joule, J. A.; Mills, K. Heterocyclic Chemistry; Blackwell Science Ltd. 2000; p 362.
    36. (a) Corey, E. J.; Estreicher, H. J. Am. Chem. Soc. 1978, 100. 6294. (b) Seebach, D.; Colvin, E. W.; Weller, T. Chimia 1979, 33, 1. (c) Barrett, A. G. M.; Graboski, G. G. Chem. Rev. 1986, 86, 751. (d) Rosini, G.; Ballini, R. Synthesis 1988, 833. (e) Kabalka, G. W.; Guindi, L. H. M.; Varma, R. S. Tetrahedron 1990, 46, 7443. (f) Lewis, R. J.; Moodie, R. B. J. Chem. Soc., Perkin Trans. 2 1997, 563. (g) Adams, J. P.; Paterson, J. R. J. Chem. Soc., Perkin Trans. 1 1999, 749. (h) Adams, J. P.; Paterson, J. R. J. Chem. Soc., Perkin Trans. 1 2000, 3695. (i) Perekalin, V. V.; Lipina, E. S.; Berestovitskaya, V. M.; Efremov, D. A. Nitroalkenes, Conjugated Nitro Compounds; Wiley & Sons, Ltd.: Chichester, 1994. (j) Olah, G. A.; Malhotra, R.; Narang, S. C. Nitration: Methods and Mechanisms; VCH: New York, 1989.
    37. (a) Ono, N. The Nitro group in Organic Synthesis; Wiley-VCH: New York, 2001. (b) Barret, A. G. M.; Graboski, G. G. Chem. Rev. 1986, 86, 751.
    38. (a) Buckley, G. D. J. Chem. Soc. 1947, 1494. (b) Buckley, G. D.; Ellery, E. J. J. Chem. Soc. 1947, 1497. (c) Ashwood, M. S.; Bell, L. A.; Houghton, P. G.; Wright, S. H. B. Synthesis 1988, 379.
    39. (a) Bedford, C. D.; Nielsen, A. T. J. Org. Chem. 1978, 43, 2460. (b) Hayama, T.; Tomoda, S.; Takeuchi, Y.; Nomura, Y. Tetrahedron Lett. 1983, 24, 2795. (c) Seebach, D.; Knochel, P. Helv. Chim. Acta 1984, 67, 261. (d) Seebach, D.; Giorgio, C.; Knochel, P. Tetrahedron 1985, 41, 4861. (e) Hanson, A. T.; Nillson, M. Tetrahedron 1982, 38, 389. (f) Stiver, S.; Yates, P. J. Chem. Soc., Chem. Commun. 1983, 50.
    40. (a). Retherford, C.; Yeh, M.-C. P.; Schipor, I.; Chen, H. G.; Knochel, P. J. Org. Chem. 1989, 54, 5200. (b) Retherford, C.; Knochel, P. Tetrahedron Lett. 1991, 32, 441. (c) Jubert, C.; Knochel, P. J. Org. Chem. 1992, 57, 5425. (d) Jubert, C.; Knochel, P. J. Org. Chem. 1992, 57, 5431.
    41. (a) Yao, C.-F.; Chen, W.-C.; Lin, Y.-M. Tetrahedron Lett. 1996, 37, 6339. (b) Yao, C.-F.; Kao, K.-H.; Liu, J.-T.; Chu, C.-M.; Wang, Y.; Chen,W.-C.; Lin, Y.-M.; Lin, W.-W.; Yan, M.-C.; Liu, J.-Y.; Chuang, M.-C.; Shiue, J.-L. Tetrahedron 1998, 54, 791. (c) Yan, M.-C.; Tu, Z.; Lin, C.; Yao, C.-F. Tetrahedron Lett, 2002, 43, 7991.
    42. (a) Yao, C.-F.; Yang, C.-S.; Fang, H.-Y. Tetrahedron Lett. 1997, 38, 6419. (b) Kao, K.-H.; Yang, C.-S.; Liu, J.-T; Lin, W.-W.; Fang, H.-Y.; Yao, C.-F.; Chen. C. Tetrahedron 1998, 54, 13997. (c) Yan, M.-C.; Liu, J.-Y.; Lin, W.-W.; Kao, K.-H.; Liu, J.-T; Jang, J.-J.; Yao, C.-F. Tetrahedron 1999, 55, 12493. (d) Tu, Z.; Jang, Y.; Lin, C.; Liu, J.-T.; Hsu, J.; Sastry, M. N. V. N.; Yao, C.-F. Tetrahedron 2005, 61, 10541. (e) Gao, S.; Tu, Z.; Kuo, C.-W.; Liu, J.-T.; Chu, C.-M.; Yao, C.-F. Organic & Biomolecular Chemistry 2006, 4, 2851. (f) Liu, J.-T; Lin, W.-W.; Jang, J.-J.; Liu, J.-Y.; Yan, M.-C.; Hung, C.; Kao, K.-H.; Wang, Y.; Yao, C.-F. Tetrahedron 1999, 55, 7115.
    43. (a) Harrington, P. E.; Kerr, M. A. Synlett, 1996, 1047. (b) Yadav, J. S.; Abraham, S.; Reddy, B. V. S.; Sabitha, G. Synthesis 2001, 2165. (c) Bandini, M.; Melchiorre, P.; Melloni, A.; Umani-Ronchi, A. Synthesis 2002, 1110. (d) Komoto, I.; Kobayashi, S. J. Org. Chem. 2004, 69, 680. (e) Zhan, Z.-P.; Yang, R.-F.; Lang, K. Tetrahedron Lett. 2005, 46, 3859. (f) Bartoli, G.; Bosco, M.; Giuli, S.; Giuliani, A.; Lucarelli, L.; Marcantoni, E.; Sambri, L.; Torregiani, E. J. Org. Chem. 2005, 70, 1941. (g) Lin, C.; Hsu, J.; Sastry, M. N. V.; Fang, H.; Tu, Z.; Liu, J.-T.; Yao, C.-F. Tetrahedron 2005, 61, 11751. (h) Firouzabadi, H.; Iranpoor, N.; Nowrouzi, F. Chem. Commun. 2005, 6, 789. (i) Azizi, N.; Arynasab, F.; Saidi, M. R. Org. Biomol. Chem. 2006, 4275. (j) Ballini, R.; Clemente, R. R.; Palmieri, A.; Petrini, M. Adv. Synth. Catal. 2006, 348, 191. (k) Wu, P.; Wan, Y.; Cai, J. Synlett 2008, 1193.
    44.(a) Jia, Y.-X.; Zhu, S.-F.; Yang, Y.; Zhou, Q.-L. J. Org. Chem. 2006, 71, 75. (b) Bandini, M.; Garelli, A.; Rovinetti, M.; Tommasi, S.; Umani-Ronchi, A. Chirality 2005, 17, 522. (c) Zhan, Z. P.; Lang, K. Synlett 2005, 1551.(c) Desolé, G.; Herrera, R. P.; Bici, A. Synlett 2004, 2374. (d) Herrera, R. P.; Sgarzani, V.; Bernardi, L.; Ricci, A. Angew. Chem., Int. Ed. 2005, 44, 6576. (e) Zhuang, W.; Hazell, R. G.; Jorgensen, K. A. Org. Biomol. Chem. 2005, 14, 2566.
    45. Liu, J.-T; Yao, C.-F. Tetrahedron Lett. 2001, 42, 6147.
    46. Itoh, K.; Kishimoto, S. New J. Chem. 2000, 24, 347
    47. Liu, H.; Xu, J.; Du, D. -M. Org. Lett. 2007, 9, 4725.
    48. Mahboobi, S.; Wiegrebe, W.; Popp, A. J. Nat. Prod. 1999, 62, 577.
    49. Mahboobi, S.; Popp, A. Burgemeister, T.; Schollmeyer, D. Tetrahedron: Asymmetry 1998, 9, 2369.
    50. (a) Narsaiah, A. V.; Nagaiah, K. Adv. Synth. Catal., 2004, 346, 1271. (b) Bose, D. S.; Narsaiah, A. V. Synthesis, 2001, 373. (c) Ishihara, K.; Furuya, Y.; Yamamoto, H. Angew. Chem. Int. Ed., 2002, 41, 2983. (d) Bose, D. S.; Goud, P. R. Tetrahedron Lett., 1999, 40, 747. (e) Bose, D. S.; Jayalakshmi, B. J. Org. Chem., 1999, 64, 1713. (f) Ley, S. V.; Leach, A. G.; Storer, R. I. J. Chem. Soc., Perkin Trans. 1, 2001, 358. (g) Wang, E. C.; Huang, K. S.; Chen, H. M.; Wu, C. C.; Lin, G. J. J. Chin. Chem. Soc., 2004, 51, 619.
    51. Yamto, E.; Sugasawa, S. Tetrahedron Lett., 1970, 4383.
    52. Lehnert, W. Tetrahedron Lett., 1971, 1501.
    53. Ressler, C.; Nagarajan, G. R.; Kirisawa, M.; Kashelikar, D. V. J. Org. Chem., 1971, 36, 3960.
    54. Sodeyama, T.; Kodomari, M.; Itabashi, K. Chem. Lett., 1973, 577.
    55. Saraie, T.; Ishiguro, T.; Kawashima, K.; Morita, K. Tetrahedron Lett., 1973, 2121.
    56. Hendrickson, J. B.; Schwartzman, S. M. Tetrahedron Lett., 1975, 277.
    57. Campagna, F.; Carotti, A.; Casini, G. Tetrahedron Lett., 1977, 1813.
    58. Cooper, D.; Trippett, S. Tetrahedron Lett., 1979, 1725.
    59. Olah, G. A.; Narang, S. C.; Fung, A. P.; Gupta, B. G. B. Synthesis, 1980, 657.
    60. (a) Bargar, T. M.; Riley, C. M. Synth. Commun., 1980, 10, 479. (b) Imamoto, T.; Takaoka, T.; Yokoyama, M. Synthesis, 1983, 142. (c) Saednya, A. Synthesis, 1985, 184. (d) Ketcha, D. M.; Gribble, G. W. J. Org. Chem., 1985, 50, 5451. (e) Mai, K.; Patil, G. Tetrahedron Lett., 1986, 27, 2203.
    61. (a) Brown, D. M. Adv. Org. Chem. 1963, 3, 91. (b) Cramer, F.; Schaller, H.; Staab, H. A. Ber. 1961, 94, 1632. (b) Hermans, R. J. M.; Buck, H. M. J. Org. Chem. 1988, 53, 2077. (c) Broka, C.; Hozumi, T.; Arentzen, R.; Itakurea, K. Nucleic Acids Res. 1980, 8, 5461.
    62. Baer, E.; Stancer, H. C. J. Am. Chem. Soc. 1963, 75, 4510.
    63. Liu, H. -J.; Chan, W. -H.; Lee, S. -P. Tetrahedron Lett. 1978, 19, 4461.
    64. Liu, H. -J.; Sabesan, S. I. Can. J. Chem. 1980, 58, 2645.
    65. (a) Liu, H. -J.; Lamoureux, G. V.; Brunet, M. L. Can. J. Chem. 1986, 64, 520.
    66. Liu, H. -J.; Nyangulu, J. M. Tetrahedron Lett. 1989, 30, 5097.
    67. Liu, H. -J.; Nyangulu, J. M. Tetrahedron Lett. 1988, 29, 3267.
    68. Liu, H.-J.; Nyangulu, J. M. Synth. Commun. 1989, 19, 3407.
    69. (a) Azipura, J. M.; Ganboa, I.; Cossio, F. P.; Gonzalez, A.; Arrieta, A.; Palomo, C. Tetrahedron Lett. 1984, 25, 3905. (b) Arrieta, A.; cossio , F. P.; Palomo, C. Tetrahedron 1985, 41, 1703. (c) Azipura, J. M.; Arrieta, A.; Palomo, C. Synth. Commun. 1982, 12, 967.
    70. Kim, C. W.; Chung, B. Y.; Namkung, J. Y.; Lee, J. M.; Kim. S. Tetrahedron Lett. 1990, 31, 2905.
    71. (a) Liu, H. -J.; Yu, S. -Y. Synth. Commun. 1986, 16, 1357. (b) Liu, H. -J.; Wiszniewski, V. Tetrahedron Lett. 1988, 29, 5471.
    72. Goswami, S. P.; Adak, A. K. Chem. Lett. 2003, 32, 678.
    73. Zhu, J. -L.; Chan, Y. -H. Synlett. 2008, 1250.
    74. (a) Luedeke, V. D. In Encyclopedia of Chemical Processing and Design; Mcketta, J. J., Ed.; Marcel Dekker: New York, 1978; pp 72-95. (b) Rademacher, H. In Ullmann’s Encyclopedia of Industrial Chemistry, 5th ed.; Gerhartz, W., Ed.; Wiley: New York, 1987; Vol. A8, pp 201-203. (c) Weber, J. N. In Kirk-Othmer Encyclopedia of Chemical Technology, 4th ed.; Kroschwitz, J. I., Ed.; Wiley: New York, 1990; Vol. 19, pp 500-501. (d) Wessermel, K.; Arpe H.-J. Industrial Organic Chemistry, 4th ed.; Wiley-VCH: Weinheim, Germany, 2003; pp 239-266. (e) Fisher, W. B.; Crescentini, L. In Kirk-Othmer Encyclopedia of Chemical Technology, 4th ed.; Kroschwitz, J. I., Ed.; Wiley: New York, 1990; Vol. 4, pp 827-839.
    75. (a) Owston, N. A.; Parker, A. J.; Williams, J. M. J. Org. Lett. 2007, 9, 3599. (b) Owston, N. A.; Parker, A. J.; Williams, J. M. J. Org. Lett. 2007, 9, 73. (c) Park, S.; Choi, Y.; Han, H.; Yang, S. H.; Chang, S. Chem. Commun. 2003, 1936.
    76. Mundy, B. P.; Ellerd, M. G.; Favaloro, F. G. Name Reactions and Reagents in Organic Synthesis; Wiley-VCH: New York, 2005.
    77. (a) Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry Part B; Springer, 2007. (b) Smith, M. B.; March, J. Advanced Organic Chemistry. 5th ed.; John Wiley and Sons: New York, 2001; p 1415, and references cited therein.
    78. Wang, B.; Gu, Y.; Luo, C.; Yang, T.; Yang, L. Suo, J. Tetrahedron Lett. 2004, 45, 3369.
    79. Li, D.; Shi, F. -S.; Guo, S.; Deng, Y. Tetrahedron Lett. 2005, 46, 671.
    80. (a) Chandrasekhar, S; Gopalaiah, K. Tetrahedron Lett. 2003, 44, 755. (b) Chandrasekhar, S; Gopalaiah, K. Tetrahedron Lett. 2003, 44, 7437. (c) Chandrasekhar, S; Gopalaiah, K. Tetrahedron Lett. 2002, 43, 2455. (d) Anilkumar, R.; Chandrasekhar, S. K. Tetrahedron Lett. 2000, 41, 5427.
    81. Luca, L. D.; Giacomelli, G.; Porcheddu, A. J. Org. Chem., 2002, 67, 6272.
    82. Furuya, Y.; Ishihara, K.; Yamamoto, H. J. Am. Chem. Soc. 2005, 127, 11240.
    83. Ramalingan, C.; Park, Y. -T. . J. Org. Chem. 2007, 72, 4536.
    84. Welton, T.; Wasserscheid, P. Ionic liquid in Synthesis; Wiley-VCH, Germany, 2003.
    85. Deng, Y.; Peng, J. Tetrahedron Lett. 2001, 42, 403.
    86. Ren, R. X.; Zueva, L. D.; Ou, W. Tetrahedron Lett. 2001, 42, 8441.
    87. Betti, C.; Landini, D.; Maia, A,; Pasi, M. Synlett. 2008, 908.
    88. Zhu, M.; Cha, C.; Deng, W. -P.; Shi, X. -X. Tetrahedron Lett. 2006, 47, 4861.
    89. Hashimoto, M.; Obora, Y.; Sakaguchi, S.; Ishii, Y. J. Org. Chem. 2008, 73, 2894.
    90. Kuo, C. -W.; Zhu, J. -L.; Wu, J. -D.; Chu, C. -M.; Yao, C. -F. Shia, K. -S. Chem. Commun. 2007, 301.
    91. Kobayashi, K.; Sugie, A.; Takahashi, M.; Masui, K.; Morl, A. Org. Lett. 2005, 7, 5083.
    92. Yasuhara, A.; Kanamori, Y.; Kaneko, M.; Numata, A.; Kondo, Y.; Sakamoto, T. J. Chem. Soc., Perkin Trans. 1 1999, 529.
    93. Ross, R. A. Trends Pharmacol Sci. 2007, 28, 567.
    94. Pagotto, U.; Marsicano, G.; Cota, D.; Lutz, B.; Pasquali, R. Endocrine Rev. 2006, 27, 73.
    95. Devane, W.; Hanus, L.; Breuer, A. et al. Science 1992, 258, 1946.
    96. (a) Mechoulam, R. et al. Biochem. Pharmacol. 1995, 50, 83. (b) Sugiura, T.; Kondo, S.; Sukagawa, A. et al. Biochem. Biophys. Res. Commun. 1995, 215, 89.
    97. Fowler, C. Br. J. Pharmacol. 2004, 141, 195. (b) Matias, I.; Bisogno, T.; Marzo, D. V. Int. J. Obes. 2006, 30 (Suppl. 1), S7. (c) Pacher, P.; Batkai, S.; Kunos, G. Pharmacol. Rev. 2006, 58, 389.
    98. (a) Alger, B. E. Progress in Neurobiology 2002, 68, 247. (b) Wilson, R.I.; Nicoll, R. A. Science 2002, 296, 678. (c) Freund, T. F.; Katona, I.; Piomelli, D. Physiol. Rev. 2003, 83, 1017.
    99. Petitet, F.; Donlan, M.; Michel, A. Chem. Biol. Drug Des. 2006, 67, 252.
    100. Lynn, A. B.; Herkenham, M. J. Pharmacol. Exp. Ther. 1993, 268, 1612.
    101. (a) Birch, E. A. Lancet 1889, 1, 625. (b) Donovan, M. Dublin Journal of Medical Science 1845, 26, 368. (c) Touw, M. J. Psychoact. Drugs 1981, 13, 23.
    102. Osei-Hyiaman, D.; DePetrillo, M.; Pacher, P. et al. J. Clin. Invest. 2005, 115, 1298.
    103. Berry, E. M.; Mechoulam, R. Pharmacology & Therapeutics 2002, 95, 185.
    104. (a) Lan, R. et al. J. Med. Chem. 1999, 42, 769. (b) Francisco, M. E. I. et al. J. Med. Chem. 2002, 45, 2708. (c) Nakamura-Palacios, E. M. et al. CNS Drug Rev. 1999, 5, 43.
    105. For recent reviews, see: (a) Lange, J. H. M.; Kruse, C. G. Drug Disco. Today 2005, 10, 693. (b) Muccioli, G. G.; Lambert, D. M. Expert Opin. Ther. Pat. 2006, 16, 1405. (c) Högenauer, E. K. Expert Opin. Ther. Pat. 2007, 17, 1457.
    106. (a) Lange, J. H. M.; vanStuivenberg, H. H.; Coolen, H. K. A. C.; Adolfs, T. J. P.; McCreary, A. C.; Keizer, H. G.; Wals, H. C.; Veerman, W.; Borst, A. J. M.; DeLooff, W.; Verveer, P. C.; Kruse, C. G. J. Med. Chem. 2005, 48, 1823. (b) Plummer, C. W.; Finke, P. E.; Mills, S. G.; Wang, J.; Tong, X.; Doss, G. A.; Fong, T. M.; Lao, J. Z.; Schaeffer, M. T.; Chen, J.; Shen, C. P.; Stribling, D. S.; Shearman, L. P.; Strack, A. M.; Van der Ploeg, L. H. Bioorg. Med. Chem. Lett. 2005, 15, 1441. (c) Tai, C.-L.; Hung, M.-S.; Pawar, V. D.; Tseng, S.-L.; Song, J.-S.; Hsieh, W.-P.; Chiu, H.-H.; Wu, H.-C. Hsieh, M.-T.; Kuo, C.-W.; Hsieh, C.-C.; Tsao, J.-P.; Chao, Y.-S.; Shia, K.-S. Org. Biomol. Chem. 2008, 6, 447.
    107. Although a general term “antagonist” is used herein, however, it is understandable that as demonstrated by SR141716A, assessed by the [35S]GTPS and/or cAMP assay(s),[117a-c] many CB1 receptor antagonists behave as inverse agonists. In fact, a more appropriate term “modulator” should be used to describe ligands with unknown intrinsic activity. As for known-function ligands, they are broadly classified as full agonists, partial agonists, (neutral, silent) antagonists and inverse agonists, respectively, as indicated in the literature.[117d-f] However, it should be noted that to determine a ligand’s intrinsic activity is often hard to be performed. (a) Reggio, P.H. Curr. Pharm. Des. 2003, 9, 1607. (b) Meschler, J.P. et al. Biochem. Pharmacol. 2000, 60, 1315.
    108. Rinaldi-Carmona, M. et al. J. Pharmacol. Exp. Ther. 2004, 310, 905.
    109. (a) Pi-Sunyer, F. X.; Aronne, L. J.; Heshmati, H. M.; Devin, J.; Rosenstock, J. JAMA 2006, 5, 761. (b) Thornton-Jones, Z. D.; Vickers, S. P.; Clifton, P. G. Psychopharmacology (Berlin) 2005, 179, 452. (c) Raynor, H. A.; Niemeier, H. M.; Wing, R. R. Eat. Behav. 2006, 7, 1.
    110. (a) Scheen, A. J. Lancet 2006, 368, 1660 (b) Oper, A. Nat. Rev. Drug. Discov. 2007, 6, 334.
    111. (a) Cohen, C.; Perrault, G.; Voltz, C.; Steinberg, R.; Soubrie, P. Behav. Pharmacol. 2002, 13, 451. (b) Hungund, B. L.; Basavarajappa, B. S.; Vadasz, C.; Kunos, G.; Rodriguez de Fonseca, F.; Colombo, G.; Serra, S.; Parsons, L.; Koob, G. F. Alcohol. Clin. Exp. Res. 2002, 26, 565.
    112. Xia, M.; Liotta, F.; Pan, M.; Wachter, M. P.; Lu, H. WO patent 2007061948.
    113. (a) Thornber, C. W. Chem. Soc. Rev. 1979, 8, 563. (b) Moreira, L. M.; Barreiro, E. J. Curr. Med. Chem. 2005, 12, 23. (c) Patani, G. A.; LaVoie, E. J. Chem. Rev. 1996, 96, 3147. (d) Hernandez, M. A.; Rathinavelu, A. Basic Pharmacology: Understanding Drug Action and Reaction. Taylor & Francis Group, 2006, Chapter 3, 68−71. (e) Burger, A. Prog.Drug Res. 1991, 37, 287.
    114. Lan, R.;Liu, Q.; Fan, P.; Lin, S.; Fernando, S. R.; McCallion, D.; Pertwee, R.; Makriyannis, A. J. Med. Chem. 1999, 42, 769.
    115. Noriyuki, N.; Miho, S.; Makoto, U. Tetrahedron, 2002, 58, 3561.
    116. Perrin, D. D.; Perrin, D. R. Purification of Laboratory Chemical; 4th. Ed.; Pergamon Press; New York; 1996.

    無法下載圖示 本全文未授權公開
    QR CODE