Chinese Journal of Organic Chemistry >
Synthesis of New Chiral γ-Alkoxy-2(5H)-furanone-piperazine-sulfonamide Compounds and Preliminary Evaluation of in Vitro Anticancer Activity
Received date: 2014-09-05
Revised date: 2014-10-01
Online published: 2014-10-21
Supported by
Project supported by the National Natural Science Foundation of China (Nos. 21462032, 21062014), the Research Starting Funds for Imported Talents of Ningxia University (No. 80020241), and the “211” Project in Ningxia University (No. ndzr09-1).
The enantiomerically pure 5-(S)-5-alkoxy-3,4-dibromo-2(5H)-furanones were readily prepared from furfural through a three-step sequence of bromine-promoted oxidation/acetalization of mucobromic acid with chiral (－)-menthol and (+)-borneol/recrystallization of the resulting γ-butenolides. Then the chiral γ-butenolides were reacted with piperazine through a one-pot two-step protocol combining Michael addition and elimination of hydrogen bromide, resulting in the crude furanone-piperazines, which were further toslated with a range of sulfonyl chlorides. 12 furanone-piperazine-sulfonamide complexs were efficiently obtained in moderate to excellent yields (45.3%～96.2%). All the new compounds were identified by 1H NMR, 13C NMR, IR and HRMS technology. The in vitro anti-tumor activities of these complexs against cervical cancer cell lines (Hela) were evaluated by thiazolylblue (MTT) assay method. Among them, 5-(S)-5-borneolyloxy-4-(p-nitrobenzene-sulfonamide-piperazinyl)-3-bromo-2(5H)-furanone (7k) exhibited the best inhibitory activity with an IC50 of 0.02 μmol/L, providing a new promising lead for further development of new anti-Hela drugs.
Wei Mengxue , Gao Xiaohui , Zhang He , Li Xueqiang . Synthesis of New Chiral γ-Alkoxy-2(5H)-furanone-piperazine-sulfonamide Compounds and Preliminary Evaluation of in Vitro Anticancer Activity[J]. Chinese Journal of Organic Chemistry, 2015 , 35(2) : 439 -445 . DOI: 10.6023/cjoc201409008
[1] Frydman, B.; Blokhin, A. V.; Brummel, S.; Wilding, G.; Maxuitenko, Y.; Sarkar, A.; Bhattacharya, S.; Church, D.; Reddy, V. K.; Kink, J. A.; Marton, L. J.; Valasinas, A.; Basu, H. S. J. Med. Chem. 2003, 46, 4586.
[2] Mitsche, L. A. Chem. Rev. 2005, 105, 559.
[3] Foroumadi, A.; Emami, S.; Mansouri, S.; Javidnia, A.; Saeid-Adeli, N.; Shirazi, F. H.; Shafiee. A. Eur. J. Med. Chem. 2007, 42, 985.
[4] He, Q. Q.; Liu, C. M.; Men, X. F.; Zhao, J. X. Chin. J. Med. Chem. 2005, 15, 262 (in Chinese). (何秋琴, 刘超美, 门秀峰, 赵靖霞, 中国药物化学杂志, 2005, 15, 262.)
[5] Bennett, F.; Saksena, A. K.; Lovey, R. G.; Liu, Y.-T.; Patel, N. M.; Pinto, P.; Pike, R.; Jao, E.; Girijavallabhan, V. M.; Ganguly, A. K.; Loebenberg, D.; Wang, H.; Cacciapuoti, A.; Moss, E.; Menzel, F.; Hare, R. S.; Nomeir, A. Bioorg. Med. Chem. Lett. 2006, 16, 186.
[6] Mi, J. L.; Zhou, C. H.; Bai, X. Chin. J. Antibiot. 2007, 32, 587 (in Chinese). (米佳丽, 周成合, 白雪, 中国抗生素杂志, 2007, 32, 587.)
[7] McRobb, F. M.; Crosby, I. T.; Yuriev, E.; Lane, J. R.; Capuano, B. J. Med. Chem. 2012, 55, 1622.
[8] Jiang, X. H.; Song, Y. L.; Feng, D. Z.; Long, Y. Q. Tetrahedron 2005, 61, 1281.
[9] Anandan, S.-K.; Ward, J. S.; Brokx, R. D.; Denny, T.; Bray, M. R.; Patel, D. V.; Xiao, X. Y. Bioorg. Med. Chem. Lett. 2007, 17, 5995.
[10] Li, J.; Wang, H.-W.; Ma, J.-L.; Zhu, Z.-Z.; Ji, P.; Liao, X.-C. Chem. Reag. 2014, 36, 13 (in Chinese). (李静, 王海卫, 马姣丽, 朱智志, 纪朋, 廖新成, 化学试剂, 2014, 36, 13.)
[11] Finlay, M. R. V.; Acton, D. G.; Andrews, D. M.; Barker, A. J.; Dennis, M.; Fisher, E.; Graham, M. A.; Green, C. P.; Heaton, D. W.; Karoutchi, G.; Loddick, S. A.; Morgentin, R.; Roberts, A.; Tucker, J. A.; Weir, H. M. Bioorg. Med. Chem. Lett. 2008, 18, 4442.
[12] Nguyen, T.; Sakasegawa, Y.; Doh-ura, K.; Go, M. L. Eur. J. Med. Chem. 2011, 46, 2917.
[13] Zhao, M.; Yin, J.; Huffman, M. A.; McNamara, J. M. Tetrahedron 2006, 62, 1110.
[14] Boxer, M. B.; Jiang, J. K.; Heiden, M. G. V.; Shen, M.; Skoumbourdis, A. P.; Southall, N.; Veith, H.; Leister, W.; Austin, C. P.; Park, H. W.; Inglese, J.; Cantley, L. C.; Auld, D. S.; Thomas, C. J. J. Med. Chem. 2010, 53, 1048.
[15] Sun, D.; Wang, Z.; Di, Y.; Jaen, J. C.; Labelle, M.; Ma, J.; Miao, S.; Sudom, A.; Tang, L.; Tomooka, C. S.; Tu, H.; Ursu, S.; Walker, N.; Yan, X.; Ye, Q.; Powers, J. P. Bioorg. Med. Chem. Lett. 2008, 18, 3513.
[16] Berrade, L.; Aisa, B.; Ramirez, M. J.; Galiano, S.; Guccione, S.; Moltzau, L. R.; Levy, F. O.; Nicoletti, F.; Battaglia, G.; Molinaro, G.; Aldana, I.; Monge, A.; Perez-Silanes, S. J. Med. Chem. 2011, 54, 3086.
[17] Wang, M. M.; Duan, Y. C.; Ye, X. W.; Ren, J. L.; Yu, B.; Zhang, E.; Liu, H. M. Chin. J. Org. Chem. 2013, 33, 2384 (in Chinese). (王盟盟, 段迎超, 叶先炜, 任景丽, 余斌, 张恩, 刘宏民, 有机化学, 2013, 33, 2384.)
[18] Kitson, R. R. A.; Millemaggi, A.; Taylor, R. J. K. Angew. Chem., Int. Ed. 2009, 48, 9426.
[19] Mao, B.; Geurts, K.; Fañanás-Mastral, M.; van Zijl, A. W.; Fletcher, S. P.; Minnaard, A. J.; Feringa, B. L. Org. Lett. 2011, 13, 948.
[20] Gunasekera, S. P.; McCarthy, P. J.; Kelly-Borges, M.; Lobkovsky, E.; Clardy, J. J. Am. Chem. Soc. 1996, 118, 8759.
[21] Avcibasi, H.; Anil, H.; Toprak, M. Phytochemistry 1987, 26, 2852.
[22] Miles, D. H.; Chittawong, V.; Lho, D.-S.; Payne, A. M.; de La Cruz, A. A.; Gomez, E. D.; Weeks, J. A.; Atwood, J. L. J. Nat. Prod. 1991, 54, 286.
[23] Marcos, I. S.; Escola, M. A.; Moro, R. F.; Basabe, P.; Diez, D.; Sanz, F.; Mollinedo, F.; de la Iglesia-Vicente, J.; Sierrac, B. G.; Urones, J. G. Bioorg. Med. Chem. 2007, 15, 5719.
[24] Takahashi, M.; Dodo, K.; Sugimoto, Y.; Aoyagi, Y.; Yamada, Y.; Hashimoto, Y.; Shirai, R. Bioorg. Med. Chem. Lett. 2000, 10, 2571.
[25] Brohm, D.; Philippe, N.; Metzger, S.; Bhargava, A.; Muller, O.; Lieb, F.; Waldmann, H. J. Am. Chem. Soc. 2002, 124, 13171.
[26] Fu, J. H.; Wang, Z. Y.; Hao, Z. F.; Huo, J. P. Chin. J. Org. Chem. 2011, 31, 1460 (in Chinese). (傅建花, 汪朝阳, 郝志峰, 霍景沛, 有机化学, 2011, 31, 1460.)
[27] Li, T. C.; Kang, L.; Li, X. Q.; Gao, X. H.; Zhou, X. Z. Chin. J. Synth. Chem. 2014, 22, 133 (in Chinese). (李天才, 康蕾, 李学强, 高晓慧, 周学章, 合成化学, 2014, 22, 133.)
[28] Xie, Y.; Wang, N.; Cheng, B.; Zhai, H. Org. Lett. 2011, 14, 3.
[29] Niu, D.; Hoye, T. R. Org. Lett. 2012, 14, 828.
[30] Kurbangalieva, A. R.; Devyatova, N. F.; Kosolapova, L. S.; Lodochnikova, O. A.; Berdnikov, E. A.; Litvinov, I. A.; Chmutova, G. A. Russ. Chem. Bull. Int. Ed. 2009, 58, 126.
[31] Rustullet, A.; Alibs, R.; de March, P.; Figueredo, M.; Font, J. Org. Lett. 2007, 9, 2827.
[32] Zhang, J.; Blazecka, P. G.; Curran, T. T. Tetrahedron Lett. 2007, 48, 2611.
[33] Blazecka, P. G.; Belmont, D.; Curran, T.; Pflum, D.; Zhang, J. Org. Lett. 2003, 5, 5015.
[34] Bennani, Y. L.; Gu, W.; Canales, A.; Díaz, F. J.; Eustace, B. K.; Hoover, R. R.; Jiménez-Barbero, J.; Nezami, A.; Wang, T. J. Med. Chem. 2012, 55, 1920.
[35] Guerrero, M. D.; Aquino, M.; Bruno, I.; Terencio, M. C.; Paya, M.; Riccio, R.; Gomez-Paloma, L. J. Med. Chem. 2007, 50, 2176.
[36] Wei, M. X.; Feng, L.; Li, X. Q.; Zhou, X. Z.; Shao, Z. H. Eur. J. Med. Chem. 2009, 44, 3340.
[37] Li, X.; Li, X. Q.; Liu, H. M.; Zhou, X. Z.; Shao, Z. H. Org. Med. Chem. Lett. 2012, 26, 2191.
[38] van Oeveren, A.; Jansen, J. F. G. A.; Feringa, B. L. J. Org. Chem. 1994, 59, 5999.
[39] Chen, Q.; Geng, Z.; Huang, B. Tetrahedron: Asymmetry 1995, 6, 401.
[40] Li, X.-Q.; Chen, Q.-H. Chem. J. Chin. Univ. 2001, 22, 1677 (in Chinese). (李学强, 陈庆华, 高等学校化学学报, 2001, 22, 1677.)
/
| 〈 |
|
〉 |
