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 H-1 and C-13 NMR, ESI and HRMS spectra. Compounds 2a-e and 3 showed no significant scavenging activity towards the free radicals ABTS(+)& x2d9; and NO & x2d9;, but compounds 2a and 2c showed promising activity as acetylcholinesterase inhibitors (IC50 = 78.99 +/- 2.75 mu M and 27.52 +/- 0.23 mu M, respectively).
keywords
FUROQUINOLINE ALKALOIDS; DERIVATIVES; INHIBITORS; COUMARINS; STEMS
subject category
Chemistry
authors
Ferreira, JPS; Cardoso, SM; Paz, FAA; Silva, AMS; Silva, VLM
our authors
Filipe Alexandre Almeida Paz
Principal Researcheracknowledgements
The authors would like to thank University of Aveiro and FCT/MEC for the financial support to the QOPNA (FCT UID/QUI/00062/2019), LAQV-REQUIMTE (UIDB/50006/2020) and CICECO Aveiro Institute of Materials (UIDB/50011/2020 & UIDP/50011/2020) research projects, financed by national funds and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement and to the Portuguese NMR network. Vera L. M. Silva thanks to the Assistant Professor position (within CEE-CINST/2018; since 01/09/2019) and also to the funding from national funds through the FCT-I.P., in the framework of the execution of the program contract provided in paragraphs 4, 5, and 6 of art. 23 of Law no. 57/2016 of 29 August, as amended by Law no. 57/2017 of 19 July and the Integrated Programme of SR&TD ``pAGE-Protein Aggregation Across the Lifespan'' (reference CENTRO-01-0145FEDER-000003), co-funded by Centro 2020 program, Portugal 2020 and European Union, through the European Regional Development Fund.