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

An elegant synthesis of 2-aroylfuro[3,2-c]quinolines 2a-e from quinolone-based chalcones 1a-e via bromination of the exocyclic double bond followed by furan ring formation was developed. Interestingly, during bromination the tautomerization of compounds’ 1a-e quinolin-4(1H)-one ring 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).