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 出版日期:2011-10-25 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 Online:2011-10-25 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(4a4c), 4a4c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5a5c. 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 (4a4c). 2-Alkoxy-N6-alkyl adeno-sine compounds 5a5c were acquired by aminolysis and deprotection reaction of compounds 4a4c. All compounds 5a5c have not been reported so far. The structures of compounds 5a5c 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