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Letters in Drug Design & Discovery


ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Research Article

Bimetallic Catalyzed N-arylation Used in Synthesis of Novel β-carbolines Derivatives

Author(s): Rui Cai , Li Zhu, Pengfei Wang and Yu Zhao*

Volume 17, Issue 5, 2020

Page: [520 - 525] Pages: 6

DOI: 10.2174/1570180815666181025124615

Price: $65


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.

Keywords: Bimetallic catalysis, β-carbolines-3-amide, arylation, synthesis, antiproliferative activity, 1H NMR, 13C NMR.

Graphical Abstract
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