(E)-4-硫-5-(2-溴乙烯基)尿苷/脱氧尿苷的合成及细胞毒性评价
收稿日期: 2016-05-16
修回日期: 2016-07-08
网络出版日期: 2016-08-12
基金资助
辽宁省教育厅科技（No. L2013472）、大连市科技计划（No. 2014E12SF074）、大连市金州新区科技计划（No. KJCX-ZTP2014-0009）资助项目.
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).
以尿苷（1a）或2'-脱氧尿苷（1b）类化合物为原料，经碘代、选择性氧化、Heck反应等步骤快捷、环保地合成（E）-5-（2-溴乙烯基）尿苷/（E）-5-（2-溴乙烯基）-2'-脱氧尿苷（5a/5b），再通过酯化、硫羰基化、氨解等步骤合成新化合物（E）-4-硫-5-（2-溴乙烯基）尿苷/（E）-4-硫-5-（2-溴乙烯基）-2'-脱氧尿苷（8a/8b），共得到5种新的硫代产物，其中包含2种新产物8a/8b，3种新中间体7a，7b，10.其结构通过1H NMR，13C NMR，IR，UV，HRMS，X-Ray等谱图手段进行了表征.采用3-（4，5-二甲基-2-噻唑基）-2，5-二苯基-2H-溴化四唑（MTT）实验方法对8a及其类似物进行了细胞毒性评价，发现8a/8b是潜在的抗肿瘤药物.
张晓辉 , 闫德峰 , 马克东 , 赫玲爽 , 高瑞琦 , 徐耀忠 , 李德鹏 . (E)-4-硫-5-(2-溴乙烯基)尿苷/脱氧尿苷的合成及细胞毒性评价[J]. 有机化学, 2016 , 36(12) : 2989 -2996 . DOI: 10.6023/cjoc201605026
(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.
[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
/
| 〈 |
|
〉 |
