目的对鬼臼毒素的A环及D环进行结构改造,以期获得合成潜在候选药物的关键中间体。方法以去甲表鬼臼毒素(DMEP)为起始原料,经醚裂解、甲基化、水解、PDC氧化、NaBH4还原、Swern氧化等反应制备得到了6个鬼臼毒素开环衍生物。结果与结论目标产物结构经1H-NMR、HR-MS确证,并结合构象分析和1H-NMR偶合常数的测定提出了确定D环开环类似物中C8′位构型的方法。 OBJECTIVE To structurally modify the A and D rings of podophyllotoxin in order to obtain the key intermediates for the synthesis of potential drug candidates. Methods Six podophyllotoxin ring-opening derivatives were prepared by using DMEP as the starting material, and then were cleaved by ether, methylated, hydrolyzed, PDC oxidized, NaBH4 reduced, and swern oxidized. Results and Conclusions The structure of the target product was confirmed by 1H-NMR and HR-MS. The conformational analysis and 1H-NMR coupling constants were used to determine the configuration of C8 ’in the D ring.