6-烷氧基-2-丙硫基-8-氮杂嘌呤核苷的合成及抗血小板凝聚活性评价有机化学.pdfVIP

DOI: 10.6023/cjoc201303017 研究论文 有机化学 Chinese Journal of Organic Chemistry ARTICLE 6-烷氧基-2-丙硫基-8-氮杂嘌呤核苷的合成及抗血小板凝聚活性评价 邓聪迩 李顺来 刘祥伟 杜洪光* (北京化工大学理学院 北京 100029) 摘要 2-硫代巴比妥酸(1)经过巯基的烷基化、嘧啶环硝化以及羟基的氯代三步反应得到 5-硝基-2-丙硫基-4,6-二氯嘧啶 (4); 1-O-乙酰基-2,3,5-三-O-苯甲酰基-β-D-呋喃核糖(5)经过叠氮取代及叠氮的还原反应得到 1-氨基-2,3,5-三-O-苯甲酰 基-β-D-呋喃核糖(7); 化合物 7 与 4 经过亲核取代、硝基还原、重氮化及偶联反应得到 9-[(2,3,5-三-O-苯甲酰基)-β-D- 呋喃核糖基]-2-丙硫基-6-氯-8-氮杂嘌呤(10); 化合物 10 与醇进行亲核取代及脱保护反应后, 得到 10 个未见报道的 6-烷 氧基-2-丙硫基-8-氮杂嘌呤核苷化合物(11 1 13 ). 化合物的结构经过 H NMR, C NMR, IR 以及HRMS 得到表征, 并进行了 抗血小板凝聚活性测试. 关键词 8-氮杂嘌呤核苷; 合成; 结构表征; 抗血小板凝聚 Synthesis of 6-Alkoxyl-2-propylthio-8-azapurine Nucleosides and Their Antiplatelet Aggregation Activity Evaluation Deng, Conger Li, Shunlai Liu, Xiangwei Du, Hongguang* (College of Science, Beijing University of Chemical Technology, Beijing 100029) Abstract 2-Thiobarbituric acid (1) was converted to 4,6-dichloro-5-nitro-2-propylthiopyrimidine (4) via S-alkylation, nitra- tion and chlorination. Followed by azide and reduction reaction of azido, 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose (5) was converted to 1-amino-2,3,5-tri-O-benzoyl-β-D-ribofuranose (7). 9-[(2,3,5-Tri-O-benzoyl)-β-D-ribofuranosyl]-6-chloro- 2-propylthio-8-azapurine (10) was obtained via nucleophilic substitution of 7 with 4, reduction, diazotization and coupling reaction. Nucleophilic displacement of the chloride in 10 with various alcohols and deprotection afforded 6-alkoxyl-2-propyl- thio-8-azapurine nucleosides (11). Their struc