乌苏烷型-21烯-28-羧酸酯的合成及其体外抗肿瘤活性研究.pdfVIP

·116 · 现代药物与临床 Drugs Clinic 第 29 卷 第 2 期 2014 年 2 月 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 孟艳秋，丁 一，张 萌，杨 哲 沈阳化工大学，辽宁 沈阳 110142 摘 要：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 C -羧基与卤代烃发生酯化反应，然后 C -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 28 3 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 1 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 H-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。 关键词：熊果酸；结构改造；抗肿瘤活性 中图分类号：R284.3 ；R979.1 文献标志码：A 文章编号：1674 - 5515(2014)02 - 0116 - 04 DOI: 10.7501/j.issn.1674-5515.2014.02.002 Synthesis of ursane type-2,12-diene-28-carboxylic acid ester and their antitumor activity in vitro MENG Yan-qiu, DING Yi, YANG Zhe, ZHANG Meng Shenyang University of Chemmical Technology, Shenyang 110142, China Abstract: 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 so