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2013 , Vol. 33 >Issue 08: 1720 - 1727

DOI: https://doi.org/10.6023/cjoc201303018

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
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  • 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

  网络出版日期: 2013-04-24

基金资助

国家自然科学基金(No. 21272022)资助项目.

收起

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

  • Wang Tao ,
  • Du Hongguang
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  • College of Science, Beijing University of Chemical Technology, Beijing 100029

Received date: 2013-03-12

  Revised date: 2013-04-11

  Online published: 2013-04-24

Supported by

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

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摘要

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3～8, 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

本文引用格式

汪韬 , 杜洪光 . 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[J]. 有机化学, 2013 , 33(08) : 1720 -1727 . DOI: 10.6023/cjoc201303018

Abstract

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

参考文献

[1] Jennings, L. K. Am. J. Cardiol. 2009, 103(3), 4.
[2] Camaioni, E.; Boyer, J. L; Mohanram, A. J. Med. Chem. 1998, 41(2), 183.
[3] Ingall, A. H.; Dixon, J.; Bailey, A. J. Med. Chem. 1999, 42(2), 213.
[4] Fox, S. C.; Behan, M. W. H.; Heptinstall, S. Cell Calcium 2004, 35(1), 39.
[5] Owen, T. R; Serradell, N.; Bolos, J. Drugs Future 2007, 32(10), 845.
[6] Springthorpe, B.; Bailey, A.; Barton, P. Bioorg. Med. Chem. Lett. 2007, 17(21), 6013.
[7] Eltayeb, A.; Griessmeier, K. J.; Mueller, C. E. Bioorg. Med. Chem. Lett. 2005, 15(24), 5450.
[8] Mateos, T. G.; Evans, R. J.; Heath, M. F. Res. Vet. Sci. 2002, 73(2), 171.
[9] Vasiljev, K. S.; Uri, A.; Laitinen, J. T. Neuropharmacology 2003, 45(1), 145.
[10] Zhang, Y.; Ye, J.; Hu, L. J. Thromb. Haemostasis 2012, 10(10), 2149.
[11] Kikugawa, K.; Iizuka, K.; Ichino, M. J. Med. Chem. 1973, 16(4), 358.
[12] Kikugawa, K.; Suehiro, H.; Ichino, M. J. Med. Chem. 1973, 16(12), 1381.
[13] Wu, Z. J.; Li, S. L.; Ding, Z. R.; Du, H. G. Chin. J. Org. Chem. 2011, 31(10), 1618 (in Chinese).
(吴兆军, 李顺来, 丁忠仁, 杜洪光, 有机化学, 2011, 31(10), 1618.)
[14] He, Q. W.; Du, H. G. Chin. J. Org. Chem. 2012, 32(9), 1678 (in Chinese).
(何琦文, 杜洪光, 有机化学, 2012, 32(9), 1678.)
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