SIOC English
有机化学
高级检索

有机化学 >

2013 , Vol. 33 >Issue 07: 1472 - 1477

DOI: https://doi.org/10.6023/cjoc201301045

研究论文

含噻吩并[3,2-c]吡啶α-氨基膦酸酯类衍生物的合成及生物活性的研究

  • 马姣丽 ,
  • 朱文娟 ,
  • 李静 ,
  • 纪朋 ,
  • 朱智志 ,
  • 廖新成
展开
  • a 郑州大学化学与分子工程学院 郑州 450052;
    b 河南中烟工业有限责任公司 郑州 450016

收稿日期: 2013-01-19

  修回日期: 2013-03-05

  网络出版日期: 2013-03-14

基金资助

国家自然科学基金(No. 21171149)资助项目.

收起

Synthesis and Biological Activities of α-Aminophosphonates Derivatives Containing Thieno[3,2-c]pyridine

  • Ma Jiaoli ,
  • Zhu Wenjuan ,
  • Li Jing ,
  • Ji Peng ,
  • Zhu Zhizhi ,
  • Liao Xincheng
Expand
  • a College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450052;
    b Henan Tobacco Industry Co., LTD., Zhengzhou 450016

Received date: 2013-01-19

  Revised date: 2013-03-05

  Online published: 2013-03-14

Supported by

Project supported by the National Natural Science Foundation of China (No. 21171149).

Fold

摘要

以3-噻吩甲醛和氨基乙醛缩二甲醇为原料, 经亲核加成、还原、取代、成环、甲酰化反应, 得到2-醛基噻吩并[3,2-c]吡啶(4), 然后与亚磷酸酯、芳香胺发生类Mannich反应得到一系列新型含有噻吩并[3,2-c]吡啶环的α-氨基膦酸酯类衍生物6a～6p. 所有目标化合物的结构均经1H NMR, 13C NMR, 31P NMR, IR和MS确证. 初步的生物活性测定试验表明, 在50 ug/mL浓度下, 大部分目标化合物对食管癌细胞(EC109)、人体肝癌细胞(HepG2)表现出较好的抑癌活性, 其中化合物6k和6o对人体肝癌细胞的抑制率超过90%.

关键词： α-氨基膦酸酯; 噻吩并[3,2-c]吡啶; 合成

本文引用格式

马姣丽 , 朱文娟 , 李静 , 纪朋 , 朱智志 , 廖新成 . 含噻吩并[3,2-c]吡啶α-氨基膦酸酯类衍生物的合成及生物活性的研究[J]. 有机化学, 2013 , 33(07) : 1472 -1477 . DOI: 10.6023/cjoc201301045

Abstract

A series of novel α-aminophosphonate derivatives containing thieno[3,2-c]pyridine (6a～6p), which have never been reported in literature, were synthesized from thieno[3,2-c]pyridine-2-carbaldehyde, phosphate ester and aromatic amine by the Mannich-type reaction. Thieno[3,2-c]pyridine-2-carbaldehyde (4) was produced via nucleophilic addition reaction, reduction, substitution reaction, cyclization, formylation using 3-thiophene formaldehyde and 2,2-dimethoxyethanamine as the starting material. The structures of all compounds have been confirmed by 1H NMR, 13C NMR, 31P NMR, IR and MS techniques. The preliminary results of biological tests indicated that most of the title compounds exhibit relatively good anticancer activity against EC109, HepG2 at the concentration of 50 μg/mL, especially compounds 6k and 6o have more than 90% inhibitory rate against HepG2

Key words： α-aminophosphonate; thieno[3,2-c]pyridine; synthesis

参考文献

[1] Zhou, H. B.; Cui, Z. P.; Liu, J. C. J. Huazhong Normal Univ. (Nat. Sci.) 2005, 39(3), 343 (in Chinese). (周红斌, 崔泽平, 刘建超, 华中师范大学学报(自然科学版), 2005, 39(3), 343.)
[2] Liu, J. C.; He, H. W. Chin. J. Appl. Chem. 2010, 27(10), 1161 (in Chinese). (刘建超, 贺红武, 应用化学, 2010, 27(10), 1161.)
[3] Pu, X. F.; Liu, P.; Fu, X. L. Drugs Clin. 2012, 27(1), 43 (in Chinese). (卜晓斐, 刘鹏, 付晓丽, 现代药物与临床, 2012, 27(1), 43.)
[4] Song, B. A.; Jiang, M. G.; Wu, Y. L.; He, X. Q.; Yang, S.; Jin, L. H.; Liu, G. Y. Chin. J. Org. Chem. 2003, 23, 967 (in Chinese). (宋宝安, 蒋木庚, 吴扬兰, 何湘琼, 杨松, 金林红, 刘刚, 有机化学, 2003, 23, 967.)
[5] Li, J. P.; Liu, R. J.; Hou, Y. Chin. J. Appl. Chem. 2008, 25(10), 1243 (in Chinese). (李建平, 刘锐杰, 侯瑛, 应用化学, 2008, 25(10), 1243.)
[6] TanaKa, F.; Kincshita, K.; Tanimura, R. J. Am. Chem. Soc. 1996, 118, 2332.
[7] Cao, L.; Wang, Y. G.; Song, X. J. Chin. J. Org. Chem. 2005, 25(8), 1007 (in Chinese). (曹蕾, 汪焱钢, 宋新建, 有机化学, 2005, 25(8), 1007.)
[8] Zhang, G. P.; Wang, W.; Song, B. A. Chin. J. Org. Chem. 2007, 27(2), 279 (in Chinese). (张国平, 王伟, 宋宝安, 有机化学, 2007, 27(2), 279.)
[9] Arsanious, M. H. N.; Isaac, Y. A.; Boulos, L. S. Heteroat. Chem. 2001, 12, 594.
[10] Liao, X. C.; Liu, L.; Guo, Y. C.; Cao, S. X.; Rong, C. L.; Zhao, Y. F. Chin. J. Org. Chem. 2006, 26(2), 233 (in Chinese). (廖新成, 刘伦, 郭艳春, 曹书霞, 荣垂林, 赵玉芬, 有机化学, 2006, 26(2), 233.)
[11] Wu, X. L.; Gao, W. X.; Ma, B.; Wang, Z.; Han, C.; Cao, S. X.; Liao, X. C. Chin. J. Org. Chem. 2009, 29(9), 1429 (in Chinese). (武现丽, 高伟霞, 马兵, 王珍, 韩超, 曹书霞, 廖新成, 有机化学, 2009, 29(9), 1429.)
[12] Song, B. A.; Jiang, M. G.; Wu, Y. L.; He, X. Q.; Yang, S.; Jin, L. H.; Liu, G.; Hu, D. Y. Chin. J. Org. Chem. 2003, 23, 961 (in Chinese). (宋宝安, 蒋木庚, 吴扬兰, 何湘琼, 杨松, 金林红, 刘刚, 胡德禹, 有机化学, 2003, 23, 961.)
[13] Bhagat, S.; Chakraborti, A. K. J. Org. Chem. 2007, 72, 1263.
[14] Bhagat, S.; Chakraborti, A. K. J. Org. Chem. 2008, 73, 6029.
[15] Li, J. P.; Chou, J. K.; Li, H. J. Chin. J. Org. Chem. 2011, 19(1), 78 (in Chinese). (李建平, 仇记宽, 李会娟, 有机化学, 2011, 19(1), 78.)
[16] Zhang, G. P.; Xia, Y. Chin. J. Org. Chem. 2010, 30(3), 449 (in Chinese). (张国平, 夏燕, 有机化学, 2010, 30(3), 449.)
[17] James, H. W.; Michael, L. D.; Robert, T. V. J. Heterocycl. Chem. 1993, 30(1), 289.
[18] Zhijian, L.; Joann, B.; Tom, R. Bioorg. Med. Chem. Lett. 2005, 15(23), 5311.
[19] Wang, Z.; Wu, X. L.; Gao, W. X.; Zhang, Q.; Ge, H. Y.; Liao, X. C. Chem. Reag. 2009, 31(12), 981 (in Chinese). (王珍, 武现丽, 高伟霞, 张谦, 葛会玉, 廖新成, 化学试剂, 2009, 31(12), 981.)
Options
文章导航

/

〈 〉