有机化学 ›› 2011, Vol. 31 ›› Issue (10): 1618-1623. 上一篇    下一篇

研究论文

N6-烷基-2-烷氧基腺苷化合物的合成及抗血小板凝集活性

吴兆军1,李顺来1,丁忠仁2,杜洪光*,1   

  1. (1北京化工大学理学院 北京 100029)
    (2复旦大学上海医学院 上海 200032)
  • 收稿日期:2011-03-14 修回日期:2011-04-15 发布日期:2011-05-10
  • 通讯作者: 杜洪光 E-mail:org_chem@yeah.net

Synthesis of 2-Alkoxy-N6-alkyl Adenosine Compounds and Their Anti-platelet Aggregation Activity

Wu Zhaojun1 Li Shunlai1 Ding Zhon-gren2 Du Hongguang*,1   

  1. (1 College of Science, Beijing University of Chemical Technology, Beijing 100029)
    (2 Fudan University Shanghai Medical School, Shanghai 200032)
  • Received:2011-03-14 Revised:2011-04-15 Published:2011-05-10

以鸟嘌呤核苷(1)为原料, 经羟基保护得到2,3,5-三-O-乙酰基鸟嘌呤核苷(2), 2与三氯氧磷反应得到2-氨基-6-氯-9-(2,3,5-三-O-乙酰基-β-D-呋喃核糖)嘌呤(3), 3经重氮化、水解和O-烷基化得到2-烷氧基-6-氯-9-(2,3,5-三-O-乙酰基-β-D-呋喃核糖)嘌呤(4a~4c), 4a~4c经胺解和水解脱保护反应得到12个未见报道的N6-烷基-2-烷氧基腺苷化合物5a~5c. 化合物的结构经1H NMR, 13C NMR, IR和HRMS等得到表征, 同时对合成的N6-烷基-2-烷氧基腺苷化合物进行了抗血小板凝集活性测试. 结果表明, 在测试浓度为100 μmol/L时, N6-(4-甲基苄基)-2-苄氧基腺苷(5c3)和N6-(2-苯乙基)-2-苄氧基腺苷(5c4)具有相对较低的聚集率, 具有一定的抗血小板凝集活性.

关键词: 腺苷, N6-烷基-2-烷氧基腺苷, 合成, 结构表征, 抗血小板凝集

Guanosine (1) as the starting material was protected by acetic anhydride to get 2,3,5-tri-O-acetyl-guanosine (2), then chlorinated with phosphorus oxychloride to obtain 2-amino-6-chloro- 9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine (3). Compound 3 was diazotized and hydrolyzed, subsequently reacted with several alkyl halides respectively to afford 2-alkoxy-6-chloro-9-(2,3,5-tri-O-acetyl-β- D-ribofuranosyl)purine (4a~4c). 2-Alkoxy-N6-alkyl adeno-sine compounds 5a~5c were acquired by aminolysis and deprotection reaction of compounds 4a~4c. All compounds 5a~5c have not been reported so far. The structures of compounds 5a~5c were identified by 1H NMR, 13C NMR, IR and HRMS techniques. What is more, the anti-platelet aggregation rates for the final compounds were measured. At a concentration of 100 μmol/L, the test results of the biological activity of anti-platelet aggregation showed that N6-(4-methylbenzyl)-2-benzyloxy adenosine (5c3) and N6-(2-phenethyl)-2-benzyloxy adenosine (5c4) have a relatively low aggregation rate and have a certain anti-platelet aggrega-tion activity.

Key words: adenosine, 2-alkoxy-N6-alkyl adenosine, synthesis, characterization, anti-platelet aggregation