Synthesis of 2-aroylfuro[3,2-c]quinolines from quinolone-based chalcones and evaluation of their antioxidant and anticholinesterase activities

Abstract

An elegant synthesis of 2-aroylfuro[3,2-c]quinolines 2a–e from quinolone-based chalcones 1a–evia bromination of the exocyclic double bond followed by furan ring formation was developed. Interestingly, during bromination the tautomerization of the quinolin-4(1H)-one ring of compounds 1a–e into the corresponding 4-hydroxyquinoline occurred followed by cyclization to give in a one-pot transformation, upon in situ oxidation, the 2-aroylfuro[3,2-c]quinolines 2a–e. In the bromination of the quinolone-based chalcone 1e, bearing a hydroxy group at the ortho-position of the aryl ring, two compounds were obtained; the major one was the expected 2-aroylfuro[3,2-c]quinoline 2e dibrominated in the aryl ring, due to the activating effect of the hydroxy group, and the minor was identified as 12a-bromo-6b,12a-dihydro-12H-chromeno[2′,3′:4,5]furo[3,2-c]quinolin-12-one 3. Two possible mechanistic pathways were proposed to explain the formation of compound 3. The structures of all new compounds were confirmed by ¹H and ¹³C NMR, ESI and HRMS spectra. Compounds 2a–e and 3 showed no significant scavenging activity towards the free radicals ABTS⁺˙ and NO˙, but compounds 2a and 2c showed promising activity as acetylcholinesterase inhibitors (IC₅₀ = 78.99 ± 2.75 μM and 27.52 ± 0.23 μM, respectively).