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¹H-NMR、¹³C-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-(3'S, 4'S)-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。

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 aggregation activities, and they were better than control drug ozagrel sodium. Conclusion 4-Methyl-(3'S, 4'S)-khelthiolactone derivatives have good anti-platelet aggregation activities, which could be a valuable candidate for further development.

国家自然科学基金资助项目(81101687)