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

Synthesis of 6-Alkoxyl-2-propylthio-8-azapurine Nucleosides and Their Antiplatelet Aggregation Activity Evaluation

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).化合物的结构经过1H NMR,13C NMR,IR以及HRMS得到表征,并进行了抗血小板凝聚活性测试.

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-ribofiaranose （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-propylthio-8-azapurine nucleosides （11）. Their structures were identified by 1H NMR, 13C NMR, IR and HRMS techniques. Moreover, the antiplatelet aggregation activities of compounds 11 were measured.