Background: Natural occurring β-Carbolines alkaloids are abundant in the plant kingdom or other organisms, and they were found to possess good antitumor activity through multiple mechanisms. Based on previous summarized SARs of β-carboline derivatives, the modification on pyridine ring would have a great impact on their antitumor activities. Therefore, we plan to synthesized arylated β-carboline-3-amides to find more valuable β-Carbolines derivatives.

Methods: A novel bimetallic Pd(OAc)2/AgOAc catalyst system was developed for the amidation of aryl iodides under acid condition. A series of N-arylated β-carbolines derivatives were synthesized using this method. The structures of these compounds were confirmed by 1H NMR, 13C NMR and HRMS, and their in vitro antiproliferative activity was investigated against HepG2 and Hela tumor cell lines by MTT assay.

Results: Eleven N-arylated β-carboline-3-amides were synthesized using this bimetallic catalyzed method in 58-98% yields. These synthesized N-arylated compounds showed no antiproliferative activity at 20 μM.

Conclusion: We have discovered an efficient and bimetallic catalytic system allowing the Narylation of secondary acyclic amides. This is the first report that N-arylation of aliphatic secondary acyclic amides under acid condition.

背景：天然存在的β-卡宾林生物碱在植物界或其他生物体中含量很高，并通过多种机制发现它们具有良好的抗肿瘤活性。基于先前总结的β-咔啉衍生物的SAR，对吡啶环的修饰将对其抗肿瘤活性产生重大影响。因此，我们计划合成芳基化的β-咔啉-3-酰胺，以发现更多有价值的β-咔啉衍生物。

方法：开发了一种新型的双金属Pd（OAc）2 / AgOAc催化剂体系，用于在酸性条件下酰胺化芳基碘。使用该方法合成了一系列N-芳基化的β-咔啉衍生物。通过1 H NMR，13 C NMR和HRMS证实了这些化合物的结构，并通过MTT法研究了它们对HepG2和Hela肿瘤细胞系的体外抗增殖活性。

结果：使用该双金属催化方法合成了11种N-芳基化的β-咔啉-3-酰胺，产率为58-98％。这些合成的N-芳基化化合物在20μM下没有抗增殖活性。

结论：我们发现了一种高效的双金属催化体系，可以使仲无环酰胺的Narylation。这是关于在酸性条件下脂族仲无环酰胺的N-芳基化的首次报道。