新型芳基修饰的藤黄酸衍生物的合成及其抗肿瘤活性

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

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。

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 with3-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 by1 H 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.