1-吲哚基取代β-咔啉生物碱及其衍生物的合成和初步抗肿瘤活性

Synthesis of 1-indole substituted β-carboline alkaloid and its derivatives and evaluation of their preliminary antitumor activities

摘要: 目的设计合成eudistomin U及其6位甲氧基/溴取代衍生物和5′位溴取代衍生物并测试其抗肿瘤活性。方法以吲哚-3-甲醛或5-溴-吲哚-3-甲醛和色胺或取代色胺为原料先缩合,再通过Pictet-Spengler反应环合得到四氢-β-咔啉,然后用DDQ脱氢芳构化得到目标化合物。结果合成了eudistomin U及其6位甲氧基/溴取代衍生物和5′位溴取代衍生物,利用核磁共振、质谱、高分辨质谱确认结构。结论合成了海洋生物碱eudistomin U及其一系列衍生物,初步体外抗肿瘤试验结果表明它们均具有一定的抗肿瘤活性。

Abstract: AimTo synthesize eudistomin U and its 6-OCH₃/Br derivatives and 5′-Br derivatives as antitumor agents. MethodsUsing tryptamine and indole-3-aldehyde as starting materials, through condensation, Pictet-Spengler cyclization and dehydrogenation three steps, the alkaloids and its derivatives were prepared. ResultsThe structures of the compounds were determined by ₁HNMR, MS and HRMS. Antitumor activity in vitro was tested. ConclusionEudistomin U and its derivatives were synthesized. The results showed that they all showed antitumor activities against mouse P388 strain.