研究生: |
林亭君 Ting-Jyun Lin |
---|---|
論文名稱: |
硫色烯類衍生物的合成及應用 Synthesis and Application of Thiochromene Derivatives |
指導教授: |
姚清發
Yao, Ching-Fa |
學位類別: |
碩士 Master |
系所名稱: |
化學系 Department of Chemistry |
論文出版年: | 2014 |
畢業學年度: | 102 |
語文別: | 中文 |
論文頁數: | 173 |
中文關鍵詞: | 苯並噻喃 、硫色烯衍生物 、芳香族親核性取代 、1,3-偶極環加成 、2,4,5-三取代三唑產物 |
英文關鍵詞: | Benzothiopyran, thiochromene, nucleophilic aromatic substitution, 1,3-dipolar cycloaddition, 2,4,5-trisubstituted triazoles |
論文種類: | 學術論文 |
相關次數: | 點閱:105 下載:1 |
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苯並噻喃衍生物是重要且常見的主體結構,其不僅已被廣泛的用於醫藥、有機合成中間體、功能性材及染料合成的中間體料等方面,更表現出獨特的生物活性,吸引許多的科學家投入關於苯並噻喃衍生物的合成方法和相關藥物活性方面之研究。
本論文的研究分為兩大部分,第一部分是探討在室溫下以4-二甲氨基吡啶 (DMAP),催化硫代乙酸酯與硝基苯乙烯進行分子間的1,4-麥可加成,能夠簡單且時間快速的合成出一系列高產率的硫色烯衍生物。
第二部分則是探討以一鍋化反應利用硫色烯衍生物做為起始物,再加入疊氮化鈉進行1,3-偶極環加成,可得到具有三氮唑雜環結構的中間產物,接著,加入1-氟-2-硝基苯及碳酸銫,在氧氣條件下進行芳香族親核性取代,即可獲得2,4,5-三取代的三唑產物。自從本世紀初“點擊化學”發明以來,疊氮產物已成為最重要的雜環化合物,大部分的1,2,3-三唑衍生物,不僅顯示出多樣的抗癌、抗發炎和抗菌等活性,也常被用來作為合成天然物的骨架。在此,我們提供了一種有效率且高產率合成三唑結構的方法,期望未來能廣泛應用於有機合成領域上。
The dissertation is divided into two parts summarizing the results based on the experimental works performed during the course of study. The first part includes a convenient procedure for the synthesis of Benzothiopyran (thiochromene) derivatives via the Michael addition of sodium salt of (2-formylphenyl) ethanethioate and nitrostyrene in the presence of 4-Dimethylaminopyridine (DMAP) as catalyst one pot. Benzothiopyran (thiochromene) derivatives are important and ubiquitous motif structure which is present in wide variety of pharmaceuticals, synthetic intermediates, and functional materials. Besides that some of the Benzothiopyran (thiochromene) derivatives acts as dyes. Thus, Benzothiopyran derivatives have triggered sustainably increasing attention in the synthetic and medicinal chemistry communities.
The second part describes a successful route for the one-pot two-step sequence involving a nucleophilic aromatic substitution (SNAr) of activated fluorobenzenes with azide nucleophile and in situ Huisgen cycloaddition of the resulting sodium azides with thiochromenes has been developed for a rapid access to 2,4,5-trisubstituted 1,2,3-(NH)-triazoles. Most of the 1,2,3-triazole derivatives shows anticancer activities, anti-inflammatory and antimicrobial, etc. Also often used as a backbone in the synthesis of natural products. Here, we provide an efficient and high yield method for the synthesis of triazole structure.
1-5、參考文獻
1. Htatokeyama, S.; Ochi, N.; Numata, H.; Takano, S. J. Chem. Soc., Chem. Commun. 1988, 17, 1202.
2. Bloxham, J.; Dell, C. P.; Smith, G.W. Heterocycles 1994, 38, 399.
3. Nawwar, G. A. M.;Abdelrazek, F. M.; Swcllam, R.H. Arch. Pharm. 1991, 342(11), 875.
4. (a) Zamocka, J.; Misikova, E.; Durinda, J. Pharmazie 1991,46, 610. (b) Zhuang, Q. Y.; Feng, Y. J.; Tu, S. J.; Jiang, H.; Shi, D. Q. Chin. J. Org. Chem. 2003, 23, 1245.
5. Rukachaisirikul, T.; Innok, P.; Aroonrerk, N.; Boonamnuaylap, W.; Limrangsun, S.; Boonyon, C.; Woonjina, U.; Suksamrarn, A. J. Ethnopharmacol. 2007, 110, 171.
6. (a) Abraham, K.; Wohrlin, F.; Lindtner, O. Mol Nutr Food Res. 2010, 54, 228-239. (b) Wagner, B. D. Molecules 2009, 14, 210. (c) Dong, B.; Ma, T.; Zhang, T. Acta Pharm Sin. 2011, 46, 35.
7. Perkin, W. H. J. Chem. Soc. 1877, 31, 388.
8. Bradford, P. M.; Micael, G. E.; Frank, G.; Favoloro, Jr. Named Reactions and Reagents in Organic Synthesis. John Wiley & Sons: New York. pp490.
9. Robert, K.; Kaufmann, H. K.; Michael, L.; Stock, H. Proceedings National Academy of Sciences 2011, 108, 11790.
10. Vliet, L. A.; Rodenhuis, N.; Dijkstra, D.; Wikstrom, H. J. Med. Chem. 2000, 43, 2871.
11. (a) Murray, J. B.; Paul, S.; Carter, A. E.; Fenwick, A. P.; Fosberry, D. W.; Hamprecht, M. J.; Hibbs, R. L.; Jarvest,* L. M.; Peter, H.; Milner, P. J.; O’Hanlon, A. J.; Pope, C. M.; Richardson, A. W.; David, R. W. Bioorg. Med. Chem. Lett. 2002, 12, 3171. (b) Keisuke, K.; Machiko, O.; Hiroyuki, A. Tetrahedron Lett. 1997, 38, 1805.
12. Bolognesi, M. L.; Bartolini, M.; Cavalli, A.; Andrisano, V.; Rosini, M.; Minarini, A.; Melchiorre , C. J. Med. Chem. 2004, 47, 5945.
13. Chen, Y.; Zhang, Q.; Zhang, B.; Xia, P.; Xia, Y.; Yang, Z. Y.; Kilgore, N.; Wild, C.; Morris-Natschke, S. L.; Lee, K. H. Bioorg. Med. Chem. 2004, 12, 6383.
14. Kanbe, Y.; Kim, M. H.; Nishimoto, M.; Ohtake, Y.; Tsunenari, T.; Taniguchi, K.; Ohizumi, I.; Kaiho, S.; Nabuchi, Y.; Kawata, S.; Morikawa, K.; Jo, J. C.; Kwon, H. A.; Lim, H. S.; Kim, H. Y. Bioorg. Med. Chem. Lett. 2006, 16, 4090.
15. Spruce, L. W.; Rajadhyaksha, S. N.; Berlin, K. D.; Gale, J. B.; Miranda, E. T.; Ford, W. T.; Blossey, E. C.; Verma, A. K.; Hossain, M. B.; Helm, D.; Breitman, T. R. J. Med. Chem. 1987, 30, 1474.
16. Arnoldi, A.; Bonsignori, A.; Melloni, P.; Merlini, L.; Quadri, M. L.; Rossi, A. C. J. Med. Chem. 1990, 33, 2865.
17. (a) Bowers, W. S.; Ohta, T.; Cleere, J. S. and Marsella, P. A. Science 1976, 193, 542. (b) Tobe, S. S.; Pratt, G. E. Biochem. J. 1974, 144, 107. (c) Camps, F.; Colomina, O.; Coll, J.; Messeguer, A. Heterocyclic Chem. 1983, 20, 1115.
18. Meyers, C. Y.; Rinaldi, C.; Bonoli, L. J. Org. Chem. 1963, 28, 2440.
19. Kristy, M.; Waugh, K.; Darrell, B.; Warren, T. F.; Elizabeth, M. H.; Carrol, J. P.; Schomber, P. R.; Thompson, M. D.; Schiff, L. J. J. Med. Chem. 1985, 28, 116.
20. Arnoldi, A.; Carughi, M. Synthesis 1988, 155.
21. Gauthier, S.; Labrie, F. Tetrahedron Letters 1996, 37 , 5077.
22. Alper, H.; Xiao, W. J. J. Org. Chem. 1999, 64, 9646.
23. Rios, R.; Sunde’n, H.; Ibrahem, I.; Zhao, G. L.; Eriksson, L.; Co’rdova , A. Tetrahedron Lett.2006, 47, 8547.
24. Wang, W.; Li, H.; Wang, J.; Zu, L. J. Am. Chem. Soc. 2006, 128, 10354.
25. Dodda, R.; Mandal, T.; Zhao, C. G. Tetrahedron Lett. 2008, 49, 1899.
26. Lee, C. H.; Lee, K. J. Heterocyclic Chem. 2009, 46, 1023.
27. Sudhir C. P.; Sankar C. B. Eur. J. Org. Chem. 2013, 4816.
28. Jin, C. K.; Jeong, H. J.; Kim, M. K.; Kim, J. Y.; Yoon, Y. J.; Lee, S. G. Synlett 2001, 12, 1956.
29. Hekmatshoar, R.; Javanshir, S.; Majid M. H. J. Chem. Res. 2007, 60.
30. Niu, Q.; Xu, X. F.; Sun, H. J.; Li, X. Y. Chin. J. Chem. 2012, 1.
31. 楊偉傑,第二章 硫色烯衍生物的合成,國立台灣師範大學化學系碩士論文,民101[2012]。
32. Kanehara, M.; Takahashi, H.; Teranishi, T. Angew. Chem. Int. Ed. 2008, 47, 307.
2-5、參考文獻
1. Wan, Q.; Chen, J.; Chen, G.; Danishefsky, S. J. J. Org. Chem. 2006, 71, 8244.
2. Ferreira, S. B.; Sodero, C. R.; Mariana, F.; Cardoso, C.; Emerson, S. L.; Kaiser, C. R.; Floriano, P.; Silva, J.; Ferreira, V. F. J. Med. Chem. 2010, 53, 2364.
3. Buckle, D. R.; Rockell, C. J. M.; Smith, H.; Spicer, B. A. J. Med. Chem. 1986, 29, 2262.
4. (a) Alvarez, R.; Velazquez, S.; San-Felix, A.; Aquaro, S.; Clercq, E.; Perno, C. F.; Karlsson, A.; Balzarini, J.; Camarasa, M. J. J. Med. Chem. 1994, 37, 4185. (b) Velaquez, S.; Alvarez, R.; Perez, C.; Gago, F.; Clercq, E.; Balzarini, J.; Camarasa, M. J. Antiviral Chem.Chemother. 1998, 9, 481. (c) Cai, D.; Journet, M.; Larsen, R. D. Chem. Abstr. 2000, 132, 293. (d) Perez, M. J.; Perez, A.; San Felix; Balzarini, J.; Clercq, E. D.; Camarasa, M. J. Med. Chem. 1992, 35, 2721.
5. Genin, M. J.; Allwine, D. A.; Anderson, D. J.; Barbachyn,M. R.; Emmert, D. E.; Garmon, S. A.; Graber, D. R.; Grega,K. C.; Hester, J. B.; Hutchinson, D. K.; Morris, J.; Reischer,R. J.; Ford, C. W.; Zurenko, G. E.; Hamel, J. C.; Schaadt, R. D.; Stapert, D.; Yagi, B. H. J. Med. Chem. 2000, 43, 953.
6. Brockunier, L. L.; Parmee, E. R.; Ok, H. O.; Candelore, M. R.; Cascieri, M. A.; Colwell, L. F.; Deng, L.; Feeney, W. P.; Forrest, M. J.; Hom, G. J.; MacIntyre, D. E.; Tota, L.; Wyvratt, M. J.; Fisher, M. H.; Weber, A. E. Bioorg. Med. Chem. Lett. 2000, 10, 2111.
7. Boucher, H. W.; Groll, A. H.; Chiou, C. C. Drugs 2004, 64, 1997.
8. Krcmery, V.; Barnes, J. J. Hos.p Infect. 2002, 50, 243.
9. Sabo, J. A.; Kahman, S. M. Ann Pharmacother 2000, 34, 1032.
10. 陳江飛; 苗彩雲中國臨床藥理學雜誌 2009, 25, 153.
11. Barehlesi, F.; Schimi, M.; Najvar, L. K. Antimierob Agents Che inother 2001, 45, 1355.
12. Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem. Int. Ed. 2001, 40, 2004.
13. Moore, N. M.; Lin, N. J.; Gallant, N. D.; Becker, M. L. Biomaterials 2010, 31, 1604.
14. (a) Mindt, T. L.; Struthers, H.; Brans, L.; Anguelov, T.; Schweinsberg, C.; Maes, V.; Tourwe, D.; Schibli, R. J . Am. Chem. Soc. 2006, 128, 15096. (b) Bonnet, D.; Ilien, B.; Galzi, J. L.; Riché, S.; Antheaune, C.; Hibert, M. Bioconjugate Chem. 2006, 17, 1618. (c) Li, J.; Zheng, M. Y.; Tang, W.; He, P. L.; Zhu, W. L.; Li, T. X.; Zuo, J. P.; Liu, H.; Jiang, H. L. Bioorg. Med. Chem. Lett. 2006, 16, 5009.
15. Kacprzak, K. M.; Maier, N. M.; Lindner, W. Tetrahedron Lett. 2006, 47, 8721.
16. Li, H. M.; Cheng, F. O.; Duft, A. M.; Adronov, A. J. Am. Chem. Soc. 2005, 127, 14518 .
17. Husigen, R. Angew. Chem. Int. Ed. 1963, 2, 565.
18. Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew. Chem. Int. Ed. 2002, 41, 2596.
19. (a) Boren, B. C.; Narayan, S.; Rasmussen, L. K.; Zhang, L.; Zhao, H.; Lin, Z.; Jia, G.; Fokin, V. V. J. Am. Chem. Soc, 2008, 130, 8923. (b) Zhang, L; Chen, X.; Xue, P.; Herman H. Y. Sun; Williams I. D.; Sharpless, K. B.; Fokin, V. V.; Jia G. J. Am. Chem. Soc. 2005, 127, 15998.
20. Dimroth, O.; Fester, G. Ber. 1910, 43, 2219.
21. Kim, D. K.; Kim, J. S.; Park, H. J. Bioorg. Med. Chem. Lett. 2004, 14, 2401.
22. Tsai, C. W.; Yang, S. C.; Liu, Y. M.; Wu, M. J. Tetrahedron 2009, 65, 8367.
23. Harvey, G. R. J. Org. Chem. 1966, 31, 1587.
24. Amantini, D.; Fringuelli, F.; Piermatti, O.; Pizzo, F.; Zunino, E.; Vaccaro, L. J. Org. Chem. 2005, 70, 6526.
25. Sengupta, S.; Duan, H.; Lu, W.; Petersen, J. L.; Shi, X. Org. Lett. 2008, 10, 1493.
26. Moltzen, E. K.; Pedersen, H.; Bogeso, K. P.; Meier, E.; Frederiksen, K.; Sanchez, C.; Lembal, H. L. J. Med. Chem. 1994, 37, 4085.
27. Wang, X. J.; Sidhu, K.; Zhang, L.; Campbell, S.; Haddad,N.; Reeves, D. C.; Krishnamurthy, D.; Senanayake, C. H. Org. Lett. 2009, 11, 5490.
28. Barluenga, J.; Valdes, C.; Beltren, G.; Escribano, M.; Aznar, F. Angew. Chem., Int. Ed. 2006, 45, 6893.
29. Yap, A. H.; Weinreb, S. M. Tetrahedron Lett. 2006, 47,3035.
30. Zhang, Y.; Li, X.; Li, J.; Chen, J.; Meng, X.; Zhao, M.; Chen, B. Org. Lett. 2012, 14, 26.
31. Varazo, K.; Droumaguet, C. L.; Fullard, K.; Wang, Q. Tetrahedron Letters 2009, 50, 7032.
32. Habib, P. M.; Raju, B. R.; Kavala, V.; Kuo, C. W.; Yao, C. F. Tetrahedron 2009, 65, 5799.
33. (a) Tsai, C. W.; Yang, S. C.; Liu, Y. M.; Wu, M. J. Tetrahedron 2009, 65, 8367. (b) Li, J.; Wang, D.; Zhang, Y.; Li, J.; Chen, B. Org. Lett. 2009,11, 3024. (c) Wang, X. J.; Sidhu, K.; Li, Z.; Scot, C.; Haddad, N.; Reeves, D. C.; Krishnamurthy, D.; Senanayake, C. H. Org. Lett. 2009, 11, 5490. (d) Zhang, Y.; Li, X.; Li, J.; Chen, J.; Meng, X.; Zhao, M.; Chen, B. Org. Lett. 2012, 14, 26.