新型芳基修饰的藤黄酸衍生物的合成及其抗肿瘤活性

以取代酚或羟基吡啶为原料，在无水碳酸钾存在下，与溴代醇发生威廉姆森醚合反应制得中间体--芳（杂环）氧基醇(2a~2k)； 2a~2k分别与藤黄酸通过光延反应合成了藤黄酸衍生物（3a~3k）。以DDC/HOSu为偶联剂，芳酸与3-氨基-1-丙醇经偶联反应制得中间体--芳酰氨基醇（5a~5h）; 5a~5h分别与藤黄酸通过光延反应合成了藤黄酸衍生物（6a~6h）。 2, 3, 5和6为新化合物，其结构经¹H NMR, ESI-MS和HR-MS表征。采用MTT法测定了3和6对肺腺癌细胞(A549)、肝癌细胞(HepG-2)和乳腺癌细胞(SK-BR-3)的体外抗肿瘤活性。结果表明：部分化合物对肿瘤细胞的抑制活性明显高于藤黄酸。

Synthesis and Antitumor Activities of Novel Aryl-substituted Gambogic Acid Derivatives

Aryloxy（heterocyclic）-alcohol（2a~2k） were prepared by Williamson ether reaction of substituted phenols(or hydroxypyridines) with bromo-alcohol, using K₂CO₃ as alkali. Gambogic acid derivatives(3a~3k) were synthesized by Mitsunobu reaction of 2a~2m with gambogic acid, respectively. Arycarbonyl amibo alcohols（5a~5h) were prepared by coupling reaction of aromatic acid with 3-amino-1-propanol, using DDC/HOSu as coupling agent. Gambogic acid derivatives(6a~6h) were synthesized by Mitsunobu reaction of 5a~5h with gambogic acid, respectively. 2, 3, 5 and 6 were new compounds and the structures were characterized by ¹H NMR, ESI-MS and HR-MS. The in vitro antitumor activities of 3 and 6 against human lung cancer cells(A549), human liver cancer cells(HepG-2) and human breast cancer cells(SK-BR-3) were investigated by MTT method. The results showed that some of the compounds exhibited better antitumor activities than gambogic acid.