有机化学 ›› 2013, Vol. 33 ›› Issue (08): 1720-1727.DOI: 10.6023/cjoc201303018 上一篇    下一篇

研究论文

9-(2-羟基乙基)-6-烷氨基-8-甲氧基-2-烷硫基嘌呤的合成及其抗血小板凝集活性

汪韬, 杜洪光   

  1. 北京化工大学理学院 北京 100029
  • 收稿日期:2013-03-12 修回日期:2013-04-11 出版日期:2013-08-25 发布日期:2013-04-24
  • 通讯作者: 杜洪光 E-mail:dhg@mail.buct.edu.cn
  • 基金资助:

    国家自然科学基金(No. 21272022)资助项目.

Synthesis of 6-Alkylamino-2-alkylthio-9-(2-hydroxyethyl)-8-methoxy-purines and Their Anti-platelet Aggregation Activities

Wang Tao, Du Hongguang   

  1. College of Science, Beijing University of Chemical Technology, Beijing 100029
  • Received:2013-03-12 Revised:2013-04-11 Online:2013-08-25 Published:2013-04-24
  • Supported by:

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

以6-氯鸟嘌呤(1)为原料, 与乙酸-2-溴-乙酯反应得到9-乙酰氧基乙基-2-氨基-6-氯嘌呤(2), 2经溴代得到9-乙酰氧基乙基-2-氨基-6-氯-8-溴嘌呤(3), 3在甲醇中与甲醇钠反应得到9-(2-羟基乙基)-2-氨基-8-甲氧基-6-氯嘌呤(4), 对4的羟基进行乙酰化保护得到9-乙酰氧基乙基-2-氨基-8-甲氧基-6-氯嘌呤(5), 5经重氮化反应后再与二烷基二硫醚反应得到9-乙酰氧基乙基-8-甲氧基-2-烷硫基-6-氯嘌呤(6), 6与胺进行亲核取代反应得到9-乙酰氧基乙基-6-烷氨基-8-甲氧基-2-烷硫基嘌呤(7), 7的羟基脱保护后得到9-(2-羟基乙基)-6-烷氨基-8-甲氧基-2-烷硫基嘌呤(8). 合成了24个未见报道的化合物38, 它们的结构经1H NMR, 13C NMR, IR及HRMS等手段得到表征, 并对9个目标化合物8进行了抗血小板凝集活性测试.

关键词: 嘌呤衍生物, 合成, 结构表征, 抗血小板凝集

2-Amino-6-chloropurine (1) was reacted with 2-bromoethyl acetate to yield 9-acetoxyethyl-2-amino-6-chloro-purine (2), which was treated with NBS to afford 9-acetoxyethyl-2-amino-8-bromo-6-chloropurine (3). 3 was reacted with sodium methanol to afford 2-amino-6-chloro-9-(2-hydroxyethyl)-8-methoxypurine (4), and then 4 was treated with acetic anhydride to yield 9-acetoxyethyl-2-amino-6-chloro-8-methoxypurine (5). After that 5 was diazotized and reacted with dialkyl disulfide to yield 9-acetoxyethyl-2-alkylthio-6-chloro-8-methoxypurine (6) and 6 was treated with amine to afford 9-acetoxyethyl-6-alkylamino-2-alkylthio-8-methoxypurine (7). Deprotection of hydroxyl group in compound 7 provided target compound 8. All 24 novel compounds 3~8 were acquired and their structures were identified by 1H NMR, 13C NMR, IR and HRMS techniques. Besides, the anti-platelet aggregation activities of the nine target compounds were tested.

Key words: purine derivatives, synthesis, characterization, anti-platelet aggregation