高等学校化学学报 ›› 2013, Vol. 34 ›› Issue (11): 2524-2530.doi: 10.7503/cjcu20130198

• 有机化学 • 上一篇    下一篇

6-取代氨基-2-烷硫基腺苷化合物的合成及抗血小板凝聚活性

魏永吉, 李顺来, 于明武, 杜洪光   

  1. 北京化工大学理学院, 北京 100029
  • 收稿日期:2013-03-05 出版日期:2013-11-10 发布日期:2013-05-03
  • 作者简介:杜洪光,男,博士,教授,主要从事药物合成研究,E-mail:dhg@mail.buct.edu.cn
  • 基金资助:

    国家自然科学基金(批准号:21272022)资助.

Synthesis of 6-Amino-2-alkylthio Adenosine and Their Anti-platelet Aggregation Activity

WEI Yong-Ji, LI Shun-Lai, YU Ming-Wu, DU Hong-Guang   

  1. College of Science, Beijing University of Chemical Technology, Beijing 100029, China
  • Received:2013-03-05 Online:2013-11-10 Published:2013-05-03

摘要:

以鸟苷(1)为原料, 经过糖环保护得到2',3',5'-三-O-乙酰基鸟嘌呤核苷(2), 化合物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-呋喃核糖基)嘌呤(3), 化合物3经重氮化后再与二烷基二硫醚反应得到2-烷硫基-6-氯-9-(2',3',5'-三-O-乙酰基-β-D-呋喃核糖基)嘌呤(4a~4d), 化合物4a~4d与胺进行亲核取代反应后, 脱去糖环保护得到12个新型的6-取代氨基-2-烷硫基腺苷化合物(5a~5l). 采用1H NMR, 13C NMR, IR和高分辨质谱(HRMS)对目标化合物的结构进行了确证, 并对所有化合物进行了体外抗血小板聚集活性测试. 结果表明, 当测试浓度为10 μmol/L时, 化合物5a~5l仍具有一定的抗凝活性, 其中, 6-(3-苯基丙基)氨基-2-丙硫基腺苷(5d)活性最为显著, 抑制率可达90.2%.

关键词: 嘌呤衍生物, 抗血小板聚集, 结构表征

Abstract:

Some purine derivatives are effective inhibitors of platelet aggregation. 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 with isoamyl nitrite and then reacted with dialkyl disulfides to afford 2-alkyl(aryl)thio-6-chloro-9-(2',3',5'-tri-O-acetyl-β-D-ribofuranosyl)purines(4a-4d). 6-Amino-2-alkylthio adenosine(5a-5l) were acquired by aminolysis and deprotection reaction of compounds 4a-4d. The structures of the compounds were identified by 1H NMR, 13C NMR, IR and high resolution mass spectrometer(HRMS). In addition, the platelet aggregation rates(PAR) for the final compounds were measured. The results show that these compounds have a certain anti-platelet aggregation activity under 10 μmol/L. 6-(3-Phenyl propyl)azyl-2-propylthio adenosine has the most significant activity, the PAR was up to 9.8%.

Key words: Purine derivative, Anti-platelet aggregation, Structural characterization

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