Vol 66 No 2 (2021): Journal of the Chilean Chemical Society
Original Research Papers


Miguel Zárraga Olavarría
Universidad de Concepción
Mohamed Dahrouch
Universidad de Concepción
Esteban Lisboa
Universidad de Concepción
Patricia Arroyo
Universidad de Concepción
Alberto Miranda
Universidad Metropolitana de Ciencias de la Educación
Published June 13, 2021
  • hydrophobic,
  • TRPV1
How to Cite
Zárraga Olavarría, M., Dahrouch, M., Lisboa, E., Arroyo, P., & Miranda, A. (2021). SYNTHESIS OF 6-TERT-OCTYL AND 6,8-DITERT-BUTYL COUMARINS, TWO COUMARINS OF BIOLOGICAL INTEREST. Journal of the Chilean Chemical Society, 66(2), 5220-5222. Retrieved from


In this study, the synthesis of new coumarins with aliphatic chains is discussed. The incorporation of the 6-tert-octyl and 6,8-ditert-butyl chains into a coumarin structure from alkylphenols, allows obtaining hydrophobic coumarins with good yields. These coumarins can be potential modulators of TRPV1 receptors. Synthesis and spectroscopic data of these new coumarins are analyzed.




  1. - M. Nikolaeva-Koleva, L. Butron, S. González-Rodríguez, S. et al. A capsaicinoid-based soft drug, AG1529, for attenuating TRPV1-mediated histaminergic and inflammatory sensory neuron excitability. Sci Rep 11, 246 (2021).
  2. - M. Iftinca, M. Defaye & C. Altier, TRPV1-Targeted Drugs in Development for Human Pain Conditions. Drugs (2020).
  3. M.A. Tabrizi, P.G. Baraldi, S. Baraldi, S. Gessi, S. Merighi, P.A. Borea Medicinal chemistry, pharmacology, and clinical implications of TRPV1 receptor antagonists Med Res Rev., 4 (2017), pp. 936-983.
  4. M.A. Gouda, B.M. Hussein, A. El-Demerdash, M.E. Ibrahim, M. Salem, M.H. Helal & W.S. Hamama, A Review: Synthesis and Medicinal Importance of Coumarins and their Analogues (Part II). Current Bioactive Compounds, 16, 993-1008 (2020).
  5. a) A. Stefanachi, F. Leonetti, L. Pisani, M. Catto, A. Carotti, Coumarin: A Natural, Privileged and Versatile Scaffold for Bioactive Compounds. Molecules, 23, 250. (2018). b) M.A. Gouda, A.A. Abu‐Hashem, M.A. Salem, M.H. Helal, M. Al‐Ghorbani, W.S. Hamama, Recent progress on coumarin scaffold‐based anti‐microbial agents (Part III). J Heterocyclic Chem.; 57: 3784– 3817 (2020).
  6. F.C. Meotti, J.V. Ardenghi, J.B. Pretto, M.M. Souza, J. d’ Ávila Moura, A. Cunha Junior, C. Soldi, Moacir G. Pizzolatti and A. R. S. Santos. Antinociceptive properties of coumarins, steroid and dihydrostyryl-2-pyrones from Polygala sabulosa (Polygalaceae) in mice. Journal of Pharmacy and Pharmacology, 58: 107–112 (2006).
  7. Hai-Ning Lyu,Ning-Ning Wei,Peng-Fei Tu,KeWei Wang &Yong Jiang, A new coumarin from Murraya alata activates TRPV1 channel Natural Product Letters, Vol. 34, 1068-1073, ( 2020).
  8. A. Szallasi & M. Sheta Targeting TRPV1 for pain relief: limits, losers and laurels, Expert Opinion on Investigational Drugs, 21:9, 1351-1369 (2012), DOI: 10.1517/13543784.2012.704021
  9. - C. Lespay Rebolledo, P. Sotelo-Hitschfeld, S. Brauchi, M. Zárraga Olavarría,
  10. Design and synthesis of conformationally restricted capsaicin analogues based in the 1, 3, 4-thiadiazole heterocycle reveal a novel family of transient receptor potential vanilloid 1 (TRPV1) antagonists. Eur J Med Chem Vol. 66, 193-203, (2013).
  11. a) B. Benso, C. Lespay-Rebolledo, L. Flores, M. Zárraga, S. Brauchi, Chalcones Derivatives as Potent Inhibitors of TRPV1 Activity. Biophysical Journal. 114(3) (2018).
  12. b) B. Benso, D. Bustos, M. Zarraga, W. Gonzalez, J. Caballero, S. Brauchi, Chalcone derivatives as non-canonical ligands of TRPV1 Int J Biochem Cell Biol 1121:18-23 (2019).
  13. L. F. Lindoy, G. V. Meehan, and N. Svenstrup, Mono- and Diformylation of 4-Substituted Phenols: A New Application of the Duff Reaction, Synthesis, 1029 (1998).
  14. R. Aldred, R. Johnston, D. Levin, J. Neilan, Magnesium-mediated ortho-specific formylation and formaldoximation of phenols, J. Chem. Soc., Perkin Trans. 1, 1823-1831 (1994)

Copyright @2019 | Designed by: Open Journal Systems Chile Logo Open Journal Systems Chile Support OJS, training, DOI, Indexing, Hosting OJS

Code under GNU license: OJS PKP