Chinese Journal of Organic Chemistry >
Synthesis of (E)-4-Thio-5-(2-bromovinyl)uridine/Deoxyuridine and Its Characterization and Cytotoxicity
Received date: 2016-05-16
Revised date: 2016-07-08
Online published: 2016-08-12
Supported by
Project Supported by the Science and Technology Project of Liaoning Provincial Department of Education (No. L2013472), the Science-technology Plan Projects of Dalian Government (No. 2014E12SF074), the Science-technology Plan Projects of Dalian Jinzhou New Area Government (No. KJCX-ZTPY-2014-0009).
(E)-4-Thio-5-(2-brominevinyl)uridine/2'-deoxyuridine (8a/8b) were efficiently synthesized in an environmental friendly way from uridine/2'-deoxyuridine (1a/1b) that were first transformed to (E)-(2-brominevinyl)uridine/2'-deoxyuridine (5a/5b) via iodination, selective oxidation, and Heck reaction steps. The resulting products 5a/5b were then converted to the targets 8a/8b through esterification, thio-reaction of carbonyl, and hydrolysis steps. Two new compounds 8a/8b and three new intermediates 7a, 7b, 10 were obtained, and their structures have been fully characterized by 1H NMR, 13C NMR, IR, UV, HR-MS and X-Ray. The study of 8a and their derivatives regarding cytotoxicity was carried out by using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) experiment method, and the initial findings suggest that (E)-4-thio-5-(2-brominevinyl)uridine/2'-deoxyuridine (8a/8b) would be potential antitumor drugs.
Zhang Xiaohui , Yan Defeng , Ma Kedong , He Lingshuang , Gao Ruiqi , Xu Yaozhong , Li Depeng . Synthesis of (E)-4-Thio-5-(2-bromovinyl)uridine/Deoxyuridine and Its Characterization and Cytotoxicity[J]. Chinese Journal of Organic Chemistry, 2016 , 36(12) : 2989 -2996 . DOI: 10.6023/cjoc201605026
[1] Wigerinck, P.; Pannecouque, C.; Snoeck, R. Med. Chem. 1991, 34, 2883.
[2] Erikson, R. L.; Szybalski, W. Radiat. Res. 1963, 20, 252.
[3] Franken, N. A.; Van Bree, C.; Veltmaat, M. A.; Rodermond, H. M.; Haveman, J.; Barendsen, G. W. J. Radiat. Res. (Tokyo) 2001, 42, 179.
[4] Pridgeon, S. W.; Heer, R.; Taylor, G. A. Br. J. Cancer 2011, 104, 1869.
[5] Gemenetzidis, E.; Shavorskaya, O.; Xu, Y. Z. Dermatol. Treatment 2013, 24, 209.
[6] Reelfs, O.; Karran, R.; Young, A. R. Photochem. Photobiol. Sci. 2012, 11, 148.
[7] Massey, M.; Xu, Y. Z.; Karran, P. Curr. Biol. 2011, 11, 1142.
[8] Ying, H.-Y.; Zhang, X.-H.; Xu, Y.-Z. J. Mol. Struct. 2011, 27, 398(in Chinese).(银鸿雁, 张晓辉, 徐耀忠, 分子科学学报, 2011, 27, 398.)
[9] Wang, J.; Zheng, X. -F.; Cao, H.-Y.; Zhang, X. -H. J. Lumin. 2013, 34, 361(in Chinese).(王健, 郑学仿, 曹洪玉, 张晓辉, 发光学报, 2013, 34, 361.)
[10] Zhai, H.-X. M. S. Thesis, Dalian University, Dalian, 2014(in Chinese).(翟红秀, 硕士论文, 大连大学, 大连, 2014.)
[11] Jones, A. S.; Verhelst, G.; Walker, R. T. Tetrahedron Lett. 1979, 20, 4415.
[12] Wang, C.-J.; Xie, F.; Zhang, W.-B. Chin. J. Org. Chem. 2008, 28, 503(in Chinese).(王春娟, 谢芳, 张万斌, 有机化学, 2008, 28, 503.)
[13] Huo, S.-H.; Li, D. P.; Wang, J.; Zhang, X. H. J. Mol. Sci. 2013, 29, 392(in Chinese).(霍书华, 李德鹏, 王健, 张晓辉, 分子科学学报, 2013, 29, 392.)
[14] Lapucha, A. R. Synthesis 1987, 256.
[15] Kaneko, K.; Katayama, H.; Wakabayashi, T.; Kumonaka, T. Synthesis 1988, 152.
[16] Sheldrick, G. M. Acta Crystallogr. 2008, A64, 112.
[17] Saenger, W. J. Am. Chem. Soc. 1972, 94, 621.
[18] Parkanyi, L.; Kalman, A.; Czugler, M.; Kovacs, T.; Walker, R. T. Nucleic Acids Res. 1987, 15, 4111.
[19] Robins, M. J.; Barr, P. J.; Giziewicz, J. Can. J. Chem. 1982, 60, 554.
[20] Bui, N. M.; Gillet, R.; Dumont, P. Appl. Radiat. Isot. 1965, 16, 337.
[21] Rong, F. G.; Soloway, A. H. Nucleosides Nucleotides 1986, 29, 213.
[22] Ashwell, M.; Jones, A. S.; Sayers, R. Tetrahedron 1987, 43, 4601.
[23] Jones, A. J.; Rahim, S. G.; Walker, R. T.; De Clercq, E. J. Med. Chem. 1981,24,759
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