Skip to main content
SpringerLink
Log in

Efficient synthesis and free-radical scavenging capacity of new 2,4-substituted tetrahydroquinolines prepared via BiCl3-catalyzed three-component Povarov reaction, using N-vinylamides

  • Full-Length Paper
  • Published:
Molecular Diversity Aims and scope Submit manuscript

Abstract

Efficient synthesis of new structurally different 2-(het)aryl-4-amidyl-substituted tetrahydroquinolines 8–29 is reported. The synthesis based on BiCl3-catalyzed three-component Povarov reaction between anilines, (het)aryl aldehydes and enamides offers a fast, safe, and cheap way for efficient tetrahydroquinoline libraries construction. Using N-vinylamides (N-vinylpyrrolidin-2-one and N-vinylacetamide) in this reaction, it was possible to obtain two series of different cis tetrahydroquinolines with antioxidant properties. Among 14 tested compounds, 7 tetrahydroquinolines revealed a prominent anti-radical capacity, equal or higher than that of the commercial antioxidants. Being the most active molecule, the N-[2-(α-furanyl)-6-methoxy-1,2,3,4-tetrahydroquinolin-4-yl] acetamide 21 was ca. 2.2-fold more potent than the well-known antioxidant, vitamin E (α-tocopherol).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Arya P, Joseph R, Gan Z, Rakic B (2005) Exploring new chemical space by stereocontrolled diversity-oriented synthesis. Chem Biol 12: 163–180. doi:10.1016/j.chembiol.2005.01.011

    Article  PubMed  CAS  Google Scholar 

  2. Boger DL, Weinreb S (1987) Hetero Diels–Alder methodology in organic synthesis. Academic Press, San Diego

    Google Scholar 

  3. Weinreb SM (1991) [4 + 2] Cycloadditions. In: Trost BM, Fleming I (eds) Comprehensive organic synthesis. Pergamon, Oxford, pp 401–512

    Chapter  Google Scholar 

  4. Tan DS (2005) Diversity-oriented synthesis exploring the intersections between chemistry and biology. Nat Chem Biol 1: 74–84. doi:10.1038/nchembio0705-74

    Article  PubMed  CAS  Google Scholar 

  5. Arya P, Durieux P, Chen Z-X, Joseph R, Leek D (2004) Stereoselective diversity-oriented solution and solid-phase synthesis of tetrahydroquinoline-based polycyclic derivatives. J Comb Chem 6: 54–64. doi:10.1021/cc034053z

    Article  PubMed  CAS  Google Scholar 

  6. Arya P, Couve-Bonnaire S, Durieux P, Laforce O, Kumar R, Leek DM (2004) Solution- and solid-phase synthesis of natural product-like tetrahydroquinoline-based polycyclics having a medium size ring. J Comb Chem 6: 735–745. doi:10.1021/cc049935s

    Article  PubMed  CAS  Google Scholar 

  7. Spring DR (2003) Diversity-oriented synthesis; a challenge for synthetic chemists. Org Biomol Chem 1: 3867–3870. doi:10.1039/B310752N

    Article  PubMed  CAS  Google Scholar 

  8. Spandl RJ, Bender A, Spring DR (2008) Diversity-oriented synthesis; a spectrum of approaches and results. Org Biomol Chem 6: 1149–1158. doi:10.1039/B719372F

    Article  PubMed  CAS  Google Scholar 

  9. Kouznetsov VV, Astudillo L, Vargas LY, Cazar ME (2004) Synthesis of some secondary amine derivatives bearing a heteroaryl fragment. J Chil Chem Soc 49: 107–203. doi:10.4067/S0717-97072004000400010

    Article  Google Scholar 

  10. Inserra PF, Ardestani SK, Watson RR (1997) Antioxidants and immune function. In: Garewal HS (ed) Antioxidant and disease prevention. CRC Press, Boca Raton, pp 19–29

    Google Scholar 

  11. MDL Drug Data Report (MDDR) database: http://www.akosgmbh.de/Symyx/software/databases/mddr.htm

  12. Meier HR, Evans S (1989) N-Substituted tetrahydroquinolines for use as antioxidants in lubricants. U.S. Patent 4828741, 9 May

  13. Meier HR, Evans S (1990) N-Substituted tetrahydroquinolines for use as antioxidants in lubricants. U.S. Patent 4919832, 24 Apr

  14. Rasberger M (1983) Tetrahydroquinoline as an antioxidant for lubricants. EP0072349A2, 16 Feb

  15. Nishiyama T, Suzuki T, Hasiguchi Y, Shiotsu S, Fujioka M (2002) Antioxidant activity of aromatic cyclic amine derivatives. Polym Degrad Stab 75: 549–554. doi:10.1016/S0141-3910(01)00258-0

    Article  CAS  Google Scholar 

  16. Nishiyama T, Hasiguchi Y, Sakata T, Sakaguchi T (2003) Antioxidant activity of the fused heterocyclic compounds, 1,2,3,4-tetahydroquinolines, and related compounds—effect of ortho-substituents. Polym Degrad Stab 79: 225–230. doi:10.1016/S0141-3910(02)00285-9

    Article  CAS  Google Scholar 

  17. De Koning AJ (2002) The antioxidant ethoxyquin and its analogues: A review. Int J Food Properties 5: 451–461. doi:10.1081/JFP-120005797

    Article  CAS  Google Scholar 

  18. Błaszczyk A, Skolimowski J (2006) Comparative analysis of cytotoxic, genotoxic and antioxidant effects of 2,2,4,7-tetramethyl-1,2,3,4-tetrahydroquinoline and ethoxyquin on human lymphocytes. Chem-Biol Interact 162: 70–80. doi:10.1016/j.cbi.2006.05.008

    Article  PubMed  Google Scholar 

  19. Dorey G, Lockhart B, Lestage P, Casara P (2000) New quinolinic derivatives as centrally active antioxidants. Bioorg Med Chem Lett 10: 935–939. doi:10.1016/S0960-894X(00)00122-0

    Article  PubMed  CAS  Google Scholar 

  20. Panteleon V, Marakos P, Pouli N, Mikros E, Andreadou I (2003) Synthesis, conformational analysis and free radical scavenging activity of some new Spiropyranoquinolinones. Chem Pharm Bull 51: 522–529. doi:10.1248/cpb.51.522

    Article  PubMed  CAS  Google Scholar 

  21. Kouznetsov VV, Vargas Méndez LY, Muñoz Acevedo A (2010) 3′,4′-Dihydrospiro[piperidine-4,2′-(1′H)quinoline] derivatives as new antioxidant agents with acetylcholinesterase inhibitory property. Lett Drug Des Discov 7: 710–715

    CAS  Google Scholar 

  22. Kouznetsov VV, Bohórquez A, Astudillo L, Fierro R (2006) An efficient synthesis of new C-2 aryl substituted quinolines based on three component imino Diels–Alder reaction. Mol Divers 10: 29–37. doi:10.1007/s11030-006-2344-8

    Article  PubMed  CAS  Google Scholar 

  23. Kouznetsov VV, Mora Cruz U, Zubkov FI, Nikitina EV (2007) An Efficient synthesis of isoindolo[2,1-a]quinoline derivatives via imino Diels–Alder and intramolecular Diels–Alder with furan methodologies. Synthesis 375–384. doi:10.1055/s-2007-965875

  24. Kouznetsov VV, Meléndez Gómez CM, Bermúdez Jaimes JH (2010) Transformations of 2-aryl-4-(2-oxopyrrolinidyl-1)-1,2,3,4-tetrahydro-quinolines, cycloadducts of the BiCl3-catalyzed three component Povarov reaction: oxidation and reduction processes towards new potentially bioactive 2-arylquinoline derivatives. J Heterocycl Chem 47: 1148–1152. doi:10.1002/jhet.44

    Article  CAS  Google Scholar 

  25. Salvador JAR, Pinto RMA, Silvestre SM (2009) Recent advances of bismuth(III) salts in organic chemistry: application to the synthesis of heterocycles of pharmaceutical interest. Curr Org Synth 6: 426–470

    Article  CAS  Google Scholar 

  26. Katritzky A, Rachwal B, Rachwal S (1995) Reactions of N-alkyl-N-phenyl-1H-benzotriazole-1-methanamines with N-vinylamides and N-vinylcarbazole. A convenient synthesis of 4-(dialkylamino)-tetrahydroquinolines. J Org Chem 60: 3993–4001. doi:10.1021/jo00118a014

    Article  CAS  Google Scholar 

  27. Talukdar S, Chen C-T, Fang J-M (2000) A stereoselective route to polysubstituted tetrahydroquinolines by benzotriazole-promoted condensation of aliphatic aldehydes and aromatic amines. J Org Chem 65: 3148–3153. doi:10.1021/jo000033x

    Article  PubMed  CAS  Google Scholar 

  28. Zhang W, Guo Y, Liu Z, Jin X, Yang L, Liu Z-L (2005) Photochemically catalyzed Diels–Alder reaction of arylimines with N-Vinylpyrrolidinone and N-vinylcarbazole by 2,4,6-triphenylpyrylium salt: synthesis of 4-heterocycle-substituted tetrahydroquinoline derivatives. Tetrahedron 61: 1325–1333. doi:10.1016/j.tet.2004.11.042

    Article  CAS  Google Scholar 

  29. Zhou Y, Jia X, Li R, Liu Z, Liu Z, Wu L (2005) Nitrosonium (NO +) initiated and cation radical-mediated imino Diels–Alder reaction. Tetrahedron Lett 46: 8937–8939. doi:10.1016/j.tetlet.2005.10.083

    Article  CAS  Google Scholar 

  30. Damon DB, Dugger R, Magnus-Aryitey G, Ruggeri R, Wester R, Tu M, Abramov Y (2006) Synthesis of the CETP inhibitor Torcetrapib: the resolution route and origin of stereoselectivity in the iminium ion cyclization. Org Process Res Dev 10: 464–471. doi:10.1021/op060014a

    Article  CAS  Google Scholar 

  31. Hadden M, Nieuwenhuyezen M, Potts D, Stevenson PJ, Thompson N (2001) Synthesis and reactivity of hexahydropyrroloquinolines. Tetrahedron 57: 5615–5624

    Article  CAS  Google Scholar 

  32. Guo C, Yang J, Wei J, Li Y, Xu J, Jiang Y (2003) Antioxidant activities of peel, pulp and seed fractions of common fruits as determined by FRAP assay. Nutr Res 23: 1719–1726. doi:10.1016/j.nutres.2003.08.005

    Article  CAS  Google Scholar 

  33. Prior RL, Hoang H, Gu L, Wu X, Bacchiocca M, Howard L, Hampsch-Woodill M, Huang D, Ou B, Jacob R (2003) Assays for hydrophilic and lipophilic antioxidant capacity (oxygen radical absorbance capacity (ORAC FL)) of plasma and other biological and food samples. J Agric Food Chem 51: 3273–3279. doi:10.1021/jf0262256

    Article  PubMed  CAS  Google Scholar 

  34. Sanchez-Moreno C, Larrauri JA, Saura-Calixto F (1998) A procedure to measure the antiradical efficiency of polyphenol. J Sci Food Agric 76: 270–276. doi:10.1002/(SICI)1097-0010(199802)76:2<270

    Article  CAS  Google Scholar 

  35. Mulabagal V, Alexander-Lindo RL, DeWitt DL, Nair MG (2008) Functional food components of Antigonon leptopustea. Food Chem 106: 487–492. doi:10.1016/j.foodchem.2007.06.013

    Article  Google Scholar 

  36. Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C (1999) Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radical Biol Med 26: 1231–1237

    Article  CAS  Google Scholar 

  37. Muñoz-Acevedo A, Vargas Méndez LY, Stashenko EE, Kouznetsov VV (2011) Improved Trolox® equivalent antioxidant capacity assay for efficient and fast search of new antioxidant agents. Anal Chem Lett 1: 86–102

    Google Scholar 

  38. Thorisson S, Gunstone FD, Hardy R (1992) Some oxidation products of ethoxyquin including those found in autoxidising systems. Chem Phys Lipids 60: 263–271

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratorio de Química Orgánica y Biomolecular, Escuela de Química, Universidad Industrial de Santander, A.A. 678, Bucaramanga, Colombia

    Vladimir V. Kouznetsov, Luz K. Luna Parada & John H. Bermudez

  2. Grupo de Investigación en Compuestos Heterocíclicos, Programa de Química, Facultad de Ciencias Básicas, Universidad del Atlántico, A.A. 1890, Barranquilla, Colombia

    Carlos M. Meléndez Gómez

  3. Grupo de Investigaciones Ambientales, Facultad de Química Ambiental, Universidad Santo Tomás, A.A. 1076, Bucaramanga, Colombia

    Leonor Y. Vargas Méndez

  4. Departamento de Química y Biología, Universidad del Norte, A.A. 1569, Barranquilla, Colombia

    Amner Muñoz Acevedo

Authors
  1. Vladimir V. Kouznetsov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carlos M. Meléndez Gómez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Luz K. Luna Parada
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. John H. Bermudez
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Leonor Y. Vargas Méndez
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Amner Muñoz Acevedo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vladimir V. Kouznetsov.

Electronic Supplementary Material

The Below is the Electronic Supplementary Material.

ESM 1 (DOC 2,682 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kouznetsov, V.V., Gómez, C.M.M., Parada, L.K.L. et al. Efficient synthesis and free-radical scavenging capacity of new 2,4-substituted tetrahydroquinolines prepared via BiCl3-catalyzed three-component Povarov reaction, using N-vinylamides. Mol Divers 15, 1007–1016 (2011). https://doi.org/10.1007/s11030-011-9330-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11030-011-9330-5

Keywords

Search

Navigation