去甲斑蝥素-半乳糖衍生物的合成与抗癌活性

设计并合成了肝靶向抗癌前药去甲斑蝥素-半乳糖(NCTD-Gal)偶联物。以去甲斑蝥素为原料，经氨基酸修饰后，再通过酰化、氢解、糖苷化和脱乙酰基反应合成去甲斑蝥素-半乳糖衍生物。合成了7个新β-O-糖苷化合物，结构通过IR、 MS、 ¹H NMR和元素分析确证。对产物4a进行了初步小鼠体内抗肿瘤实验，结果显示，4a中、高剂量组抑瘤率明显高于NCTD组，表明半乳糖苷化对NCTD抗癌作用有一定提高。

Synthesis and anticancer activity of norcantharidin-galactose derivatives

To design and synthesize the hepatic targeting anticancer prodrug with norcantharidin (NCTD-Gal) conjugating structure, galactosylated NCTD derivatives were synthesized from NCTD analogues modified by a series of amino acids via acylation, hydrolysis, glycosylation and deacetylation. Seven new compounds were synthesized as beta-O-glycosides and characterized by IR, MS, NMR and element analysis. The compound 4a was chosen for the inchoate antitumor experiments on mice. The result showed that the antitumor inhibition rate of 4a groups with medium and high dose are clearly higher than that of NCTD group, which suggests that anticancer effect of NCTD is improved at a certain degree by galactosylation.