目的 设计合成去甲斑蝥素酰胺类衍生物,并评价其抗肝癌活性.方法 以呋喃和顺丁烯二酸酐为起始原料,通过Diels-Alder反应成环,再经氧化和胺化反应制得目标化合物.评估目标化合物对人肝癌细胞 HepG-2的抑制活性.结果与结论 合成了 16个化合物,其中11个未见文献报道,其结构经1H-NMR、 13C-NMR、IR、HR-MS谱确证.体外活性测试结果表明,化合物6f展现出较强抑制HepG-2细胞生长的活性,其IC50值为(7. 10±0.04)μmol.L-1,与阳性对照组顺铂的IC50值[(9. 83 ±0. 28) μmol-L-1]相当.初步探讨了目标化合物的抗肝癌活性构效关系,为斑蝥素衍生物进一步结构改造提供参考.“,”In China,hepatoma is one of the most common malignant tumors,which seriously endangers health. Based on our previous work, a series of norcantharidin amides derivatives(5a-5g,6a-6g) were designed and synthesized,including sixteen compounds of epoxidation of 5,6 position double bonds(5a-5g) and amidation of anhydride (6a-6g),among which eleven compounds are first reported. Thus their anti-hepatoma were evaluated in the HepG-2 cell line. Using furan and maleic anhydride as the materials, compounds 5a-5g and 6a-6g were prepared by Diels-Alder,oxidation and amination reactions. The chemical structures of the compounds were confirmed by 1H-NMR,13C-NMR, IR and HR-MS spectra. In vitro anti-hepatoma activities were tested by MTT assay. Compound 6f[ (7. 10 ±0. 04) μmol-L11] is commensurate with cisplatin[ (9. 83 ±0. 28) μmol? L-1] in anti-hepatoma activity,and it can be studied as a leading compound of anti-hepatoma. Antitumor activity data showed that the existence of pyridine moiety was in favour of anti-hepatoma activity. The 5a-5g of the epoxidation structure have the same laws of anti-hepato-ma activity, with the dehydronorcantharidin derivatives (6a-6g). However, when the substituents are constructed,the former of anti-hepatoma activity is lower than that of the latter. The above results provide a direction for further study on the study of the effects of anti-hepatoma.