6-烃氧基-2-烷硫基腺苷化合物的合成及抗血小板凝聚活性

Synthesis of 6-alkoxy-2-alkylthio Adenosine and Their Anti-platelet Aggregation Activity

摘要:

本文以鸟嘌呤核苷（1）为原料，经羟基保护得到2′,3′,5′-三-O-乙酰基鸟嘌呤核苷（2），2与三氯氧磷反应得到2-氨基-6-氯-9-(2′,3′,5′-三-O-乙酰基-β-D-呋喃核糖基)嘌呤（3），3再进行重氮-烷硫化反应，生成2-烷硫基-6-氯-9-(2′,3′,5′-三-O-乙酰基-β-D-呋喃核糖基)嘌呤（4），4与醇进行亲核取代反应同时脱去糖环保护得到8个6-烃氧基-2-烷硫基嘌呤腺苷化合物（5）。化合物的结构经1H NMR、13C NMR、IR和HRMS表征，同时对合成的目标化合物进行了体外抗血小板凝聚活性测试。结果表明，在测试浓度为10 μmol/L时，6-(2-呋喃甲基)氧基-2-丙硫基腺苷具有较高的抗血小板凝聚活性。

Abstract:

Guanosine (1) as the starting material was protected by acetic anhydride to get 2′,3′,5′-tri-O-acetyl-guanosine(2) , then chlorinated with phosphorus oxychloride to obtain 2-amino-6-chloro-9-(2′,3′,5′-tri-O-acetyl-β-D-ribofuranosyl)purine(3). Further diazotization-sulfenylation processes gave rise to 2-alkylthio-6-chloro-9-(2′,3′,5′-tri-O-acetyl-β-D-ribofuranosyl)purines(4). 6-Alkoxy-2-alkylthio adenosine (5) were acquired by aromatic nucleophilic substitution and deprotection reaction. The structures of the compounds were identified by 1H NMR、13C NMR、IR and HRMS. What is more, platelet aggregation rate(PAR) for the compounds were measured. The results show that, these compounds have a certain anti-platelet aggregation activity under 10μmol/L, wherein 6-(2-furanylmethyl)oxy-2-propylthio adenosine presents the most significant activity.