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

Year: 2024

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide This paper presents a copper(I)-catalyzed intramolecular tandem acylation/ O -arylation of methyl 2-[2-(2-bromophenyl)acetamido]benzoates for the synthesis of benzofuro[3,2- c ]quinolin-6(5 H )-ones under mild conditions. The combination of CuI, 1,10-phenanthroline, and K 2 CO 3 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- c ]quinolin-6(5 H )-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 50 value of 0.41 μM.

Source: The Journal of Organic Chemistry

DOI: 10.1021/acs.joc.4c02813