目的 設(shè)計(jì)并合成凱林硫代內(nèi)酯衍生物,并測(cè)定其體外血小板聚集抑制活性。方法 以7-羥基-4-甲基香豆素為原料,經(jīng)親核取代、克萊森重排、硫化反應(yīng)、sharpless不對(duì)稱羥基化、酯化反應(yīng)制備目標(biāo)化合物5a～5h;采用微量反應(yīng)板酶標(biāo)儀比濁法評(píng)價(jià)目標(biāo)化合物的抗血小板聚集活性。結(jié)果 合成了8個(gè)新化合物,其結(jié)構(gòu)經(jīng)¹H-NMR、¹³C-NMR及MS確證?；钚詼y(cè)試結(jié)果表明,化合物5h、5b的活性強(qiáng)于陽(yáng)性對(duì)照藥奧扎格雷鈉,具有抗血小板聚集活性。結(jié)論 4-甲基-(3'S, 4'S)-凱林硫代內(nèi)酯衍生物具有良好的抗血小板聚集活性,值得進(jìn)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.

國(guó)家自然科學(xué)基金資助項(xiàng)目(81101687)