Copper(I)-Catalyzed Intramolecular Tandem Acylation/-Arylation Under Mild Conditions: Synthesis of Benzofuro[3,2-]quinolin-6(5)-ones and G-Quadruplex-Targeting Analogues

Overview

Journal J Org Chem

Publisher American Chemical Society

Specialty Chemistry

Date 2024 Dec 27

PMID 39726144

Authors

Show-Jen Chiou

Yi-Chien Lin

Yi-Fu Chang

Yu-Fen Chen

Tzu-Hao Lo

Chia-Shen Tsai

Hung-Chun Liao

Pei-Yi Tsai

Shih-Hsien Chuang

Jiann-Jyh Huang

Affiliations

Soon will be listed here.

Abstract

This paper presents a copper(I)-catalyzed intramolecular tandem acylation/-arylation of methyl 2-[2-(2-bromophenyl)acetamido]benzoates for the synthesis of benzofuro[3,2-]quinolin-6(5)-ones under mild conditions. The combination of CuI, 1,10-phenanthroline, and KCO in DMSO was found to be the optimal reaction condition, producing the target products in high yields (84-99%) at 70 °C for 16 h. The tandem reaction was applicable to substrates bearing halo, electron-withdrawing, and electron-donating groups at their phenyl moieties with a broad substrate scope. Further derivation produced compounds serving as G-quadruplex DNA (G4 DNA) stabilizers. The most potent analogue, 2,9-bis{[3-(diethylamino)propyl]amino}-5-methylbenzofuro[3,2-]quinolin-6(5)-one, significantly increased the melting temperature of G4 DNA by 9.8 °C at 1.0 μM, approximately 4.6 times more selective than duplex DNA. The G4 stabilizer also showed anticancer activity, actively inhibiting MDA-MB-231 cancer cells with a GI value of 0.41 μM.

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