23-羟基白桦脂酸的30位羟基衍生物的合成及其抗肿瘤活性

目的:对天然活性化合物23-羟基白桦脂酸进行结构修饰,寻找新的抗肿瘤候选化合物。方法:将23-羟基白桦脂酸3,23位羟基经乙酰化保护以及28位酯化得23-羟基白桦脂酸酯,再与间氯过氧苯甲酸进行环氧化反应,开环及脱保护得到目标化合物。用MTT法进行抗肿瘤活性的测定。结果:所合成的新化合物6a-e和7a其结构均经过红外光谱,质谱和核磁共振氢谱确证。目标化合物6a-e的抗肿瘤活性在多个细胞系中高于23-羟基白桦脂酸。结论:23-羟基白桦脂酸的衍生物6e可作为比较有潜力的候选化合物进一步进行抗肿瘤活性研究。

Synthesis and anti-tumor activity of 30-hydroxy derivatives of 23-hydroxy betulinic acid

Aim:To improve the anti-tumor effects and to screen candidate for anti-tumor agent,30-hydroxy derivatives 6a-e and 7a were obtained from the modification of 23-hydroxy betulinic acid.Methods:After protection of the hydroxyl at C-3 and C-23 and carboxyl at C-28 of 23-hydroxy betulinic acid,the oxidation of compounds 5a-e was processed with m-chloroperoxybenzoic acid in chloroform by refluxing for 6 h.Meanwhile,the anti-tumor activity of the target compounds was tested by MTT.Results:The structures of the target compounds have been confirmed by the analytical and spectral analyses.The results showed that the anti-tumor activity of the target compounds was much potent than that of 23-hydroxy betulinic acid.Conclusion:The derivative of 23-hydroxy betulinic acid(6e) is a promising lead compound as the anti-tumor agent worth further investigation.