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Medicinal Chemistry Research

, Volume 26, Issue 7, pp 1415–1426 | Cite as

Synthesis and analgesic activity of monoterpenoid-derived alkyl-substituted chiral hexahydro-2H-chromenes

  • Irina Il’ina
  • Alla Pavlova
  • Dina Korchagina
  • Oleg Ardashov
  • Tat’yana Tolstikova
  • Konstantin Volcho
  • Nariman Salakhutdinov
Original Research

Abstract

A set of new 2-alkyl-substituted 4,7-dimethyl-3,4,4a,5,8,8a-hexahydro-2H-chromene-4,8-diols was obtained by reactions of monoterpenoid (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol with aliphatic aldehydes in the presence of montmorillonite clay K10. Synthesized compounds were evaluated for their analgesic activity in vivo using the acetic acid-induced writhing test and the hot-plate test. Five compounds showed a significant analgesic activity in the acetic acid-induced writhing test; two of them also demonstrated analgesic activity in the hot-plate test. These compounds seem to be most promising for further development.

Keywords

Terpene Chromene Heterocyclic compounds Analgesic activity Acetic acid-induced writhing test Hot-plate test 

Notes

Acknowledgements

Authors are grateful to the Russian Foundation for Basic Research (Grant No. 15-33-20198) for the financial support

Conflict of interest

The authors declare that they have no competing interests.

References

  1. Baishya G, Sarmah B, Hazarika N (2013) An environmentally benign synthesis of octahydro-2H-chromen-4-ols via modified montmorillonite K10 catalyzed Prins cyclization reaction. Synlett 24:1137–1141CrossRefGoogle Scholar
  2. Bondalapati S, Reddy UC, Saha P, Saikia AK (2011) An efficient synthesis of dihydro- and tetrahydropyrans via oxonium–ene cyclization reaction. Org Biomol Chem 9:3428–3438CrossRefPubMedGoogle Scholar
  3. Bunyapaiboonsri T, Yoiprommarat S, Intereya K, Rachtawee P, Hywel-Jones NL, Isaka M (2009) Isariotins E and F, spirocyclic and bicyclic hemiacetals from the entomopathogenic fungus Isaria tenuipes BCC 12625. J Nat Prod 72:756–759CrossRefPubMedGoogle Scholar
  4. Eddy NB, Leimbach D (1953) Studies of anesthetics. J Pharmacol Exp Ther 107:385–393PubMedGoogle Scholar
  5. Il’ina IV, Volcho KP, Korchagina DV, Barkhash VA, Salakhutdinov NF (2007) Reactions of allyl alcohols of the pinane series and of their epoxides in the presence of montmorillonite clay. Helv Chim Acta 90:353–368CrossRefGoogle Scholar
  6. Il’ina IV, Volcho KP, Mikhalchenko OS, Korchagina DV, Salakhutdinov NF (2011) Reactions of verbenol epoxide with aromatic aldehydes containing hydroxy or methoxy groups in the presence of montmorillonite clay. Helv Chim Acta 94:502–513CrossRefGoogle Scholar
  7. Il’ina I, Mikhalchenko O, Pavlova A, Korchagina D, Tolstikova T, Volcho K, Salakhutdinov N, Pokushalov E (2014) Highly potent analgesic activity of monoterpene-derived (2S,4aR,8R,8aR)-2-aryl-4,7-dimethyl-3,4,4a,5,8,8a-hexahydro-2H-chromene-4,8-diols. Med Chem Res 23:5063–5073CrossRefGoogle Scholar
  8. Koster R, Anderson M, De Beer EJ (1959) Acetic acid for analgesic screening. Fed Proc 18:412–415Google Scholar
  9. Macedo A, Wendler EP, Dos Santos AA, Zukerman-Schpector J, Tiekink ERT (2010) Solvent-free catalized synthesis of terahydropyran odorants: the role of SiO2·p-TSA catalyst on the Prins-cyclization reaction. J Braz Chem Soc 21:1563–1571CrossRefGoogle Scholar
  10. Mikhalchenko O, Il’ina I, Pavlova A, Morozova E, Korchagina D, Tolstikova T, Pokushalov E, Volcho K, Salakhutdinov N (2013) Synthesis and analgesic activity of new heterocyclic compounds derived from monoterpenoids. Med Chem Res 22:3026–3034CrossRefGoogle Scholar
  11. Mikhalchenko OS, Volcho KP, Salakhutdinov NF (2013) Synthesis of heterocyclic compounds by interaction of aldehydes with monoterpenoids. New developments in aldehydes research. Nova Science Publishers, NewYork, NY, p 49–80Google Scholar
  12. Mikhalchenko OS, Korchagina DV, Volcho KP, Salakhutdinov NF (2014) Formation of the compounds with an epoxychromene framework: role of the methoxy groups. Helv Chim Acta 97:1406–1421CrossRefGoogle Scholar
  13. Nazimova E, Pavlova A, Mikhalchenko O, Il’ina I, Korchagina D, Tolstikova T, Volcho K, Salakhutdinov N (2016) Discovery of highly potent analgesic activity of isopulegol-derived (2R,4aR,7R,8aR)-4,7-dimethyl-2-(thiophen-2-yl)octahydro-2H-chromen-4-ol. Med Chem Res 25:1369–1383CrossRefGoogle Scholar
  14. Patrusheva OS, Zarubaev VV, Shtro AA, Orshanskaya YR, Boldyrev SA, Ilyina IV, Kurbakova SYu, Korchagina DV, Volcho KP, Salakhutdinov NF (2016) Anti-influenza activity of monoterpene-derived substituted hexahydro-2H-chromenes. Bioorg Med Chem 24:5158–5161CrossRefPubMedGoogle Scholar
  15. Pavlova A, Mikhalchenko O, Rogachev A, Il’ina I, Korchagina D, Gatilov Y, Tolstikova T, Volcho K, Salakhutdinov N (2015) Synthesis and analgesic activity of stereoisomers of 2-(3(4)-hydroxy-4(3)-methoxyphenyl)-4,7-dimethyl-3,4,4a,5,8,8a-hexahydro-2H-chromene-4,8-diols. Med Chem Res 24:3821–3830CrossRefGoogle Scholar
  16. Saha P, Reddy UC, Bondalapati S, Saikia AK (2010) A novel synthesis of oxabicyclo[3.3.1]nonanone via (3,5)-oxonium−ene reaction. Org Lett 12:1824–1826CrossRefPubMedGoogle Scholar
  17. Salakhutdinov NF, Volcho KP, Il’ina IV, Korchagina DV, Tatarova LE, Barkhash VA (1998) New reactions of isoprenoid olefins with aldehydes promoted by Al2O3-SiO2 catalysts. Tetrahedron 54:15619–15642CrossRefGoogle Scholar
  18. Sarmah B, Baishya G, Baruah RK (2014) First example of a Prins–Ritter reaction on terpenoids: a diastereoselective route to novel 4-amido-octahydro-2H-chromenes. RSC Adv 4:22387–22397CrossRefGoogle Scholar
  19. Silva Jr LF, Quintiliano SA (2009) An expeditious synthesis of hexahydrobenzo[f]isochromenes and of hexahydrobenzo[f]isoquinoline via iodine-catalyzed Prins and aza-Prins cyclization. Tetrahedron Lett 50:2256–2260CrossRefGoogle Scholar
  20. Stekrova M, Mäki-Arvela P, Kumar N, Behravesh E, Aho A, Balme Q, Volcho K, Salakhutdinov N, Murzin D (2015) Prins cyclization: synthesis of compounds with tetrahydropyran moiety over heterogeneous catalysts. J Mol Catal A Chem 410:260–270CrossRefGoogle Scholar
  21. Syubaev RD, Mashkovskii MD, Shvarts GY, Pokryshkin VI (1986) Comparative pharmacological activity of modern nonsteroidal antiinflammatory preparations. Pharm Chem J 20:17–22CrossRefGoogle Scholar
  22. Szychowski J, Truchon JF, Bennani YL (2014) Natural products in medicine: transformational outcome of synthetic chemistry. J Med Chem 57:9292–9308CrossRefPubMedGoogle Scholar
  23. Timofeeva MN, Volcho KP, Mikhalchenko OS, Panchenko VN, Krupskaya VV, Tsybulya SV, Gil A, Vicente MA, Salakhutdinov NF (2015) Synthesis of octahydro-2H-chromen-4-ol from vanillin and isopulegol over acid modified montmorillonite clays: effect of acidity on the Prins cyclization. J Mol Catal A Chem 398:26–34CrossRefGoogle Scholar
  24. Tolstikova TG, Pavlova AV, Morozova EA, Il’ina IV, Volcho KP, Salakhutdinov NF (2011) Application of 4,7-dimethyl-2-(prop-1-enyl)-3,4,4a,5,8,8a-heahydro-2H-chromen-4,8-diol as analgesic. Patent RU 2418578, 20 May 2011Google Scholar
  25. Torozova A, Mäki-Arvela P, Aho A, Kumar N, Smeds A, Peurla M, Sjöholm R, Heinmaa I, Korchagina DV, Volcho KP, Salakhutdinov NF, Murzin DYu (2015) Heterogeneous catalysis for transformation of biomass derived compounds beyond fuels: synthesis of monoterpenoid dioxinols with analgesic activity. J Mol Catal A Chem 397:48–55CrossRefGoogle Scholar
  26. Volcho KP, Salakhutdinov NF, Barkhash VA (1999) A new way to accelerate reactions catalyzed by clays. Russ J Org Chem 35:1554–1555Google Scholar
  27. Volcho KP, Tatarova LE, Korchasgina DB, Salakhutdinov NF, Aul’chenko IS, Ione KG, Barkhash VA (1994) Cycloaddition of carbonyl compounds to olefins on aluminosilicate catalysts. Zh Org Khim 30:641–653Google Scholar
  28. Yadav JS, Subba Reddy BV, Ganesh AV, Narayana Kumar GGKS (2010) Sc(OTf)3-catalyzed one-pot ene-Prins cyclization: a novel synthesis of octahydro-2H-chromen-4-ols. Tetrahedron Lett 51:2963–2966CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of SciencesNovosibirskRussian Federation
  2. 2.Novosibirsk State UniversityNovosibirskRussian Federation

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