凯林硫代内酯衍生物的合成及其体外抗血小板聚集活性研究.PDF

现代药物与临床 Drugs Clinic 第 30 卷 第 9 期 2015 年 9 月 ·1051 · • 实验研究 • 4- 甲基-(3S, 4S)-凯林硫代内酯衍生物的合成及其体外抗血小板聚集活性 研究 * * 胡梦楠，闫超群，何素海，梁泰刚 ，李青山 山西医科大学 药学院，山西 太原 030001 摘 要：目的 设计并合成凯林硫代内酯衍生物，并测定其体外血小板聚集抑制活性。方法 以 7-羟基-4- 甲基香豆素为原 料，经亲核取代、克莱森重排、硫化反应、sharpless 不对称羟基化、酯化反应制备目标化合物 5a～5h ；采用微量反应板酶 标仪比浊法评价目标化合物的抗血小板聚集活性。结果 合成了 8 个新化合物，其结构经 1 13 H-NMR 、 C-NMR 及 MS 确证。 活性测试结果表明，化合物 5h、5b 的活性强于阳性对照药奥扎格雷钠，具有抗血小板聚集活性。结论 4- 甲基-(3S, 4S)-凯 林硫代内酯衍生物具有良好的抗血小板聚集活性，值得进一步研究。 关键词：凯林硫代内酯；7-羟基-4- 甲基香豆素；奥扎格雷钠；合成；抗血小板聚集活性 中图分类号：R914 ；R973 文献标志码：A 文章编号：1674 - 5515(2015)09 - 1051 - 06 DOI: 10.7501/j.issn.1674-5515.2015.09.001 Synthesis of 4-methyl-(3′S, 4′S)-khelthiolactone derivatives and their anti-platelet aggregation activities in vitro HU Meng-nan, YAN Chao-qun, HE Su-hai, LIANG Tai-gang, LI Qing-shan School of Pharmaceutical Science, Shanxi Medical University, Taiyuan 030001, China Abstract: Objective To design and synthesize khelthiolactone derivatives, and to evaluate their anti-platelet aggregation activities in virto. Methods 7-Hydroxy-4-methyl coumarin was used as starting material to synthesize the target compounds by nucleophilic substitution reaction, claisen rearrangement, sulfuration reaction, sharpless asymmetrical dihydroxylation, and esterification reactions. The anti-platelet aggregation activities of the synthesized compounds were evaluated by microplate reader method. Results Eight novel khelthiolactone derivatives were synthesized and characterized by 1H-NMR, 13C-NMR, and MS data. The in vitro assay indicated that compounds 5h and 5b exhibited remarkable anti-platelet ag