乌苏烷型-2,12-烯-28-羧酸酯的合成及其体外抗肿瘤活性研究

目的设计合成了乌苏烷型-2,12-烯-28-羧酸酯类化合物,并对其进行了体外抗肿瘤活性研究。方法熊果酸先进行C28-羧基与卤代烃发生酯化反应,然后C3-羟基与甲基磺酰氯在0℃冰浴条件下发生甲基磺酰化反应,最后在168℃回流条件下发生消除反应,从而得到目标产物;通过MTT法对上述合成的乌苏烷型-2,12-烯-28-羧酸酯类化合物进行体外抗肿瘤活性研究。结果设计并合成了7个目标产物3a~3g,利用IR、MS和1H-NMR确证了结构;抗肿瘤活性筛选结果表明3b对A549肿瘤细胞的抑制率略低于阳性对照药吉非替尼。结论此路线操作简单,设计合理,对进一步开展熊果酸的结构改造和抗肿瘤活性研究具有一定的参考价值。

Synthesis of ursane type-2,12-diene-28-carboxylic acid ester and their antitumor activity in vitro

Objective To search for a synthetic route for synthesis ofursane type-2,12-diene-28-carboxylic acid ester and to study their antitumor activities in vitro. Methods The carboxyl group at C28 of ursolic acid reacted with halogenated hydrocarbons by esterification reaction, and the hydroxyl group at C3 reacted with methyl sufonyl chloride by methyl sulfonic acid reaction at 0 ℃. The target product was obtained after the elimination reaction at 168 ℃. The antitumor activities of the compounds were tested by MTT assay. Results Seven target products 3a--3g were synthesized, and were characterized by IR, MS and ℃H-NMR. The antitumor activity screening results showed that compound 3b exhibited lower inhibitory rate against A549 cells than gefitinib. Conclusion This route has the advantages of simple operation and reasonable design, provids some practical reference value for the further development on the structure modification ofursolic acid derivatives and study on anti-tumor activity.