目的 設(shè)計合成了烏蘇烷型-2,12-烯-28-羧酸酯類化合物，并對其進行了體外抗腫瘤活性研究。方法 熊果酸先進行C28-羧基與鹵代烴發(fā)生酯化反應(yīng)，然后C3-羥基與甲基磺酰氯在0 ℃冰浴條件下發(fā)生甲基磺酰化反應(yīng)，最后在168 ℃回流條件下發(fā)生消除反應(yīng)，從而得到目標(biāo)產(chǎn)物；通過MTT法對上述合成的烏蘇烷型-2,12-烯-28-羧酸酯類化合物進行體外抗腫瘤活性研究。結(jié)果 設(shè)計并合成了7個目標(biāo)產(chǎn)物3a～3g，利用IR、MS和1H-NMR確證了結(jié)構(gòu)；抗腫瘤活性篩選結(jié)果表明3b對A549腫瘤細(xì)胞的抑制率略低于陽性對照藥吉非替尼。結(jié)論 此路線操作簡單，設(shè)計合理，對進一步開展熊果酸的結(jié)構(gòu)改造和抗腫瘤活性研究具有一定的參考價值。

Objective To search for a synthetic route for synthesis of ursane 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 1H-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 of ursolic acid derivatives and study on anti-tumor activity.

國家自然科學(xué)基金資助項目（21372156）