SIOC English
有机化学
高级检索

有机化学 >

2013 , Vol. 33 >Issue 08: 1741 - 1748

DOI: https://doi.org/10.6023/cjoc201303017

研究论文

6-烷氧基-2-丙硫基-8-氮杂嘌呤核苷的合成及抗血小板凝聚活性评价

  • 邓聪迩 ,
  • 李顺来 ,
  • 刘祥伟 ,
  • 杜洪光
展开
  • 北京化工大学理学院 北京 100029

收稿日期: 2013-03-11

  修回日期: 2013-04-04

  网络出版日期: 2013-04-17

基金资助

国家自然科学基金(No. 21272022)资助项目.

收起

Synthesis of 6-Alkoxyl-2-propylthio-8-azapurine Nucleosides and Their Antiplatelet Aggregation Activity Evaluation

  • Deng Conger ,
  • Li Shunlai ,
  • Liu Xiangwei ,
  • Du Hongguang
Expand
  • College of Science, Beijing University of Chemical Technology, Beijing 100029

Received date: 2013-03-11

  Revised date: 2013-04-04

  Online published: 2013-04-17

Supported by

Project supported by the National Natural Science Foundation of China (No. 21272022).

Fold

摘要

2-硫代巴比妥酸(1)经过巯基的烷基化、嘧啶环硝化以及羟基的氯代三步反应得到5-硝基-2-丙硫基-4,6-二氯嘧啶(4); 1-O-乙酰基-2,3,5-三-O-苯甲酰基-β-D-呋喃核糖(5)经过叠氮取代及叠氮的还原反应得到1-氨基-2,3,5-三-O-苯甲酰基-β-D-呋喃核糖(7); 化合物7与4经过亲核取代、硝基还原、重氮化及偶联反应得到9-[(2',3',5'-三-O-苯甲酰基)-β-D-呋喃核糖基]-2-丙硫基-6-氯-8-氮杂嘌呤(10); 化合物10与醇进行亲核取代及脱保护反应后, 得到10个未见报道的6-烷氧基-2-丙硫基-8-氮杂嘌呤核苷化合物(11). 化合物的结构经过1H NMR, 13C NMR, IR以及HRMS得到表征, 并进行了抗血小板凝聚活性测试.

关键词： 8-氮杂嘌呤核苷; 合成; 结构表征; 抗血小板凝聚

本文引用格式

邓聪迩 , 李顺来 , 刘祥伟 , 杜洪光 . 6-烷氧基-2-丙硫基-8-氮杂嘌呤核苷的合成及抗血小板凝聚活性评价[J]. 有机化学, 2013 , 33(08) : 1741 -1748 . DOI: 10.6023/cjoc201303017

Abstract

2-Thiobarbituric acid (1) was converted to 4,6-dichloro-5-nitro-2-propylthiopyrimidine (4) via S-alkylation, nitration and chlorination. Followed by azide and reduction reaction of azido, 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose (5) was converted to 1-amino-2,3,5-tri-O-benzoyl-β-D-ribofuranose (7). 9-[(2',3',5'-Tri-O-benzoyl)-β-D-ribofuranosyl]-6-chloro-2-propylthio-8-azapurine (10) was obtained via nucleophilic substitution of 7 with 4, reduction, diazotization and coupling reaction. Nucleophilic displacement of the chloride in 10 with various alcohols and deprotection afforded 6-alkoxyl-2-propylthio-8-azapurine nucleosides (11). Their structures were identified by 1H NMR, 13C NMR, IR and HRMS techniques. Moreover, the antiplatelet aggregation activities of compounds 11 were measured.

Key words： 8-azapurine nucleosides; synthesis; characterization; antiplatelet aggregation

参考文献

[1] Jennings, L. K. Am. J. Cardiol. 2009, 103, 4A.
[2] Awtry, E. H.; Loscalzo, J. Circulation 2000, 101, 1206.
[3] Cattaneo, M. Drug News Perspect 2006, 19, 253.
[4] James, E.; David, E.; Cindy, L. Circulation 2003, 108, 1316.
[5] Aerschot, A.; Mamos, P.; Weyns, J. J. Med. Chem. 1993, 36, 2938.
[6] Sagi, G.; Otvos, L.; Ikeda, S. J. Med. Chem. 1994, 37, 1307.
[7] Smith, W. C.; Sidwell, W. R.; Robins, K. R. J. Med. Chem. 1972, 15, 883.
[8] Montgomery, A. J.; Thomas, J. H. J. Med. Chem. 1972, 15, 305.
[9] Matsuda, A.; Shinozaki, M.; Yamaguchi, T. J. Med. Chem. 1992, 35, 241.
[10] Estep, G. K.; Josef, A. K.; Bacon, R. E. J. Med. Chem. 1995, 38, 2582.
[11] Cox, D.; Ingall, A.; Willis, P. WO 9703084, 1997[Chem. Abstr. 1997, 126, 186328].
[12] Zhang, H. C.; Maryanoff, B. E.; Ye, H.; Chen, C. L. WO 2008054795, 2008[Chem. Abstr. 2008, 148, 517743].
[13] Ding, Z. R.; Kim, S.; Kunapuli, S. P. Mol. Pharm. 2005, 69, 338.
[14] Wu, Z. J.; Li, S. L.; Ding, Z. R.; Du, H. G. Chin. J. Org. Chem. 2011, 31, 1618 (in Chinese).
(吴兆军, 李顺来, 丁忠仁, 杜洪光, 有机化学, 2011, 31, 1618.)
[15] He, Q. W.; Du, H. G. Chin. J. Org. Chem. 2012, 32, 1678 (in Chinese).
(何琦文, 杜洪光, 有机化学, 2012, 32, 1678.)
[16] Du, H. G.; Chen, L.; Wang, S. M. CN 102250097, 2011[Chem. Abstr. 2011, 155, 683474].
[17] Bonnert, R.; Ingall, A.; Springthorpe, B.; Willis, P. WO 9828300, 1998[Chem. Abstr. 1998, 129, 95506].
[18] Storer, R.; Gosselin, G.; Griffon, J. F.; Pierra, C. WO 2007144686, 2006[Chem. Abstr. 2006, 148, 79268].
[19] Volpini, R.; Marucci, G.; Buccioni, M.; Ben, D. D.; Lambertucci, C.; Lammi, C.; Mishra, R. C.; Thomas, A.; Cristalli, G. ChemMedChem 2011, 6, 1074.
[20] Niedballa, U.; Vorbrüggen, H. J. Org. Chem. 1976, 41, 2084.
Options
文章导航

/

〈 〉