新型2,6,9-三取代嘌呤衍生物的合成及抗血小板凝集活性  

Synthesis of Novel 2,6,9-Substituted Purine Derivatives and Their Anti-platelet Aggregation Activities

作　　者：何琦文[1] 杨丽龙 陈涛[1] HE Qi-wen;YANG Li-long;CHEN Tao(State Key Laboratory of Fluorine&Nitrogen Chemicals,Xi’an Modern Chemistry Research Institute,Xi′an 710065,China)

机构地区：[1]西安近代化学研究所氟氮化工资源高效开发与利用国家重点实验室

出　　处：《合成化学》2019年第8期617-622,共6页Chinese Journal of Synthetic Chemistry

基　　金：国家自然科学基金资助项目(21272022)

摘　　要：以9-乙酰氧基乙基-2-丙硫基-6-氯嘌呤化合物为原料,经烷胺化和玻沃-布兰还原制得2-(6-烷氨基-2-丙硫基-9 H-嘌呤-9-基)乙醇(2a^2d);2a^2d与二苄基磷酰氯反应制得2-(6-烷氨基-2-丙硫基-9 H-嘌呤-9-基)乙基二苄基磷酸酯(3a^3d);3a^3d与三甲基溴硅烷反应合成了2-(6-烷氨基-2-丙硫基-9 H-嘌呤-9-基)乙基磷酸二氢酯化合物(4a^4d),化合物3与化合物4均为新化合物,其结构经1 H NMR,13 C NMR,31 P NMR,IR和HR-MS(ESI)表征。研究了3a^3d,4a^4d的抗血小板凝集活性。结果表明:含有磷酸基团的嘌呤化合物活性明显优于不含磷酸基团嘌呤化合物的活性,其中4b活性最好,抗血小板凝集活性为17.79%。2-(6-Alkylamino-2-propylt-hio-9 H-purin-9-yl)-ethanol(2a^2d)was acquired by aminolysis reaction and Bouveault-Blanc reaction from 9-acetoxyethyl-2-propylthio-6-chloropurine.Phosphorylation of 2a^2d afforded the phosphoric acid intermediates dibenzyl-2-(6-alkylamino-2-propylt-hio-9 H-purin-9-yl)ethyl phosphate(3a^3d).Finally,2-(6-alkyl-amino-2-propylthio-9 H-purin-9-yl)ethyl dihydroge phosphate(4a^4d)were synthesized by the reaction of bromotrimethylsilane with 3a^3d.3 and 4 were novel compounds.The structures were characterized by 1 H NMR,13 C NMR,31 P NMR,IR and HR-MS(ESI).Meanwhile,the anti-platelet aggregation rates of compounds 3 and 4 were measured.The results showed that the activity of purine compounds containing phosphate groups(4b)was the best,with anti-platelet aggregation rate of 17.79%.

关 键 词：嘌呤衍生物 三甲基溴硅烷 磷酰化 合成 抗血小板凝集 

分 类 号：O626[理学—有机化学] R914.5[理学—化学]