新型齐墩果酸糖苷化衍生物的合成及体外抗HCT8活性

为提高齐墩果酸的水溶性和稳定性,以齐墩果酸苷元为起始原料,对其28-COOH进行甲基化修饰后制得齐墩果酸-28-羧甲酯(1)。分别以D-半乳糖、D-葡萄糖、D-氨基葡萄糖为起始原料,通过对糖羟基的保护与去保护,得到一系列的二糖、四糖片段。通过三氯乙酰亚胺酸酯途径和对甲苯硫基途径,利用合成的糖片段对1的3-位羟基进行糖化学结构修饰,合成了4种新型的齐墩果酸糖苷化衍生物(2~5),其结构经1H NMR,13C NMR和MS(ESI)表征。采用MTT法测试了2~5对高表达人结肠癌细胞(HCT8)的体外抑制活性。结果表明:2~5对HCT8有一定的抑制作用,化合物5浓度为1×10^-3 mmol/L时,抑制率达到(98.96±0.10)%。

Synthesis and In Vitro Anti-HCT 8 Activities of Novel Oleanolic Glycoside Derivatives

In order to improve the water solubility and stability of oleic acid,oleanolic acid-28-carboxy methyl ester(1)was obtained by methylating oleanolic acid glycosides with oleanolic acid glycosides.At the same time,using D-galactose,D-glucose and D-glucosamine as starting materials,a series of disaccharide and tetranose fragments were obtained by protecting and deprotecting hydroxyl groups on sugar.Four new oleanolic acid glycosylation derivatives(2~5)were obtained by glycosylation of 3-hydroxyl groups of 1 by trichloroacetylidene ester pathway and p-toluene thio-group pathway.The structures were characterized 1H NMR,13C NMR and MS(ESI).High expression human colon cancer cell line(HCT8)was used to study the antitumor activities of 2~5 in vitro by MTT assay.The results showed that 2~5 had a certain inhibitory effect on HCT8,and the inhibition rate of compound 5 reached(98.96±0.10)%at the highest concentration of 1×10^-3 mol/L.