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Synthetic Transformations of Higher Terpenoids. 41. Synthesis and Anti-Inflammatory Activity of 4-(Carboxyalkyl)-18-nor-isopimara-7,15-Dienes

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Synthetic methods were developed for isopimaric acid derivatives, the terminal carboxylic acid of which was separated by two or three methylenes from the tricyclic skeleton. Their anti-inflammatory activity was studied. A Wittig reaction of isopimarinal (obtained from isopimaric acid) with the phosphorus ylide generated from methoxymethyl(triphenyl)phosphonium chloride using butyllithium formed a mixture of (Z)- and (E)-alkenes (54% yield) and 4-[(Z)-pentenyl]-18-nor-isopimara-7,15-diene (17% yield). Hydrolysis of the mixture of enol ethers by p-toluenesulfonic acid in Me2CO produced 4-(2-oxoethyl)-18-nor-isopimara-7,15-diene. Olefination of pimarinal and its homolog by a Horner–Wadsworth–Emmons reaction led to the corresponding ethers of (E)-alkenes (81–85% yield). Reduction of the double bond by Mg in MeOH and hydrolysis of the ethers proceeded smoothly to the corresponding 4-(carboxyalkyl)-18-nor-isopimara-7,15-dienes (74 and 88% yield). The structure of 4-(2-carboxyethyl)-18-nor-isopimara-7,15-diene was established by an X-ray crystal structure analysis. Significant anti-inflammatory activity of the new C4-modified isopimaric acid derivatives was found in in vivo tests.

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References

  1. Yu. V. Kharitonov, E. E. Shul′ts, T. V. Rybalova, A. V. Pavlova, and T. G. Tolstikova, Chem. Nat. Compd., 57, 879 (2021).

    Article  CAS  Google Scholar 

  2. G. A. Tolstikov, T. G. Tolstikova, E. E. Shults, S. E. Tolstikov, and M. V. Khvostov, Resin Acids of Russian Conifers. Chemistry and Pharmacology [in Russian], B. A. Trofimov (ed.), Geo, Novosibirsk, 2011, 395 pp.

  3. J. Zaugg, S. Khom, D. Eigenmann, I. Baburin, M. Hamburger, and S. Hering, J. Nat. Prod., 74, 1764 (2011).

    Article  CAS  Google Scholar 

  4. S. Salari, M. S. Ejneby, J. Brask, and F. Elinder, Acta Physiol., 222, e12895 (2018).

    Article  Google Scholar 

  5. Y. Imaizumi, K. Sakamoto, A. Yamada, A. Hotta, S. Ohya, K. Muraki, M. Uchiyama, and T. Ohwada, Mol. Pharmacol., 62, 836 (2002).

    Article  CAS  Google Scholar 

  6. C. Wu, K. V. Gopal, T. J. Lukas, G. W. Gross, and E. J. Moore, Eur. J. Pharmacol., 732, 68 (2014).

    Article  CAS  Google Scholar 

  7. A. Nardi, V. Calderone, S. Chericoni, and I. Morelli, Planta Med., 69, 885 (2003).

    Article  CAS  Google Scholar 

  8. M. K. Hjortness, L. Riccardi, A. Hongdusit, A. Ruppe, M. Zhao, E. Y. Kim, P. H. Zwart, B. Sankaran, H. Arthanari, M. C. Sousa, M. De Vivo, and J. M. Fox, Biochemistry, 57, 5886 (2018).

    Article  CAS  Google Scholar 

  9. R. Russo, J. Loverme, G. L. Rana, G. D’Agostino, O. Sasso, A. Calignano, and D. Piomelli, Eur. J. Pharmacol., 566, 117 (2007).

  10. E. M. Pferschy-Wenzig, O. Kunert, A. Presser, and R. Bauer, J. Agric. Food Chem., 56, 11688 (2008).

    Article  CAS  Google Scholar 

  11. X. W. Wu, Q. Wang, Q. Li, Y. M. Cui, Y. K. Pu, Q. Q. Shi, D. W. Bi, J. J. Zhang, R. H. Zhang, X. L. Li, X. J. Zhang, and W. L. Xiao, Chem. Biodiversity, 17 (12), e2000798 (2020).

    CAS  Google Scholar 

  12. L. Juanjuan, L. Yanju, W. Jing, B. Liangwu, and Z. Zhendong, Chin. J. Org. Chem., 37, 731 (2017).

    Article  Google Scholar 

  13. Y.-J. Lu, Z.-D. Zhao, Y.-X. Chen, J. Wang, S.-C. Xu, and Y. Gu, J. Asian Nat. Prod. Res., 23 (6), 545 (2021).

    Article  CAS  Google Scholar 

  14. M. A. Gromova, Yu. V. Kharitonov, M. A. Pokrovskii, I. Yu. Bagryanskaya, A. G. Pokrovskii, and E. E. Shul′ts, Chem. Nat. Compd., 55, 52 (2019).

    Article  CAS  Google Scholar 

  15. M. A. Gromova, Yu. V. Kharitonov, S. A. Borisov, D. S. Baev, T. G. Tolstikova, and E. E. Shul′ts, Chem. Nat. Compd., 57, 474 (2021).

    Article  CAS  Google Scholar 

  16. Y.-G. Suh, Y.-H. Kim, M.-H. Park, Y.-H. Choi, H.-K. Lee, J.-Y. Moon, K.-H. Min, D.-Y. Shin, J.-K. Jung, O.-H. Park, R.-O. Jeon, H.-S. Park, and S.-A. Kang, Bioorg. Med. Chem. Lett., 11, 559 (2001).

    Article  CAS  Google Scholar 

  17. Y.-G. Suh, K.-O. Lee, S.-H. Moon, S.-Y. Seo, Y.-S. Lee, S.-H. Kim, S.-M. Paek, Y.-H. Kim, Y.-S. Lee, J. M. Jeong, S. J. Lee, and S. G. Kim, Bioorg. Med. Chem. Lett., 14, 3487 (2004).

    Article  CAS  Google Scholar 

  18. K. O. Lee, K. H. Min, and Y. G. Suh, Arch. Pharm. Res., 28, 648 (2005).

    Article  CAS  Google Scholar 

  19. T. D. Drebushchak, V. A. Khan, E. N. Shmidt, Zh. V. Dubovenko, E. P. Kemertelizde, and V. A. Pentegova, Chem. Nat. Compd., 18, 49 (1982).

    Article  Google Scholar 

  20. M. C. Garcia-Alvarez, M. Paternostro, F. Piozzi, B. Rodriguez, and G. Savona, Phytochemistry, 18, 1835 (1979).

    Article  CAS  Google Scholar 

  21. F. H. Allen, O. Kenard, D. G. Watson, L. Bramer, A. G. Orpen, and R. Taylor, J. Chem. Soc., Perkin Trans. 2, S1 (1987).

    Article  Google Scholar 

  22. Cambridge Structural Database (Version 5.39), University of Cambridge, UK; F. H. Allen, Acta Crystallogr., Sect. B: Struct. Sci., 58, 380 (2002).

  23. M. A. Gromova, Yu. V. Kharitonov, T. V. Rybalova, and E. E. Shul′ts, Chem. Nat. Compd., 54, 293 (2018).

    Article  CAS  Google Scholar 

  24. Handbook for Experimental (Preclinical) Studies of New Drugs [in Russian], Meditsina, Moscow, 2005, p. 832.

  25. M. A. Timoshenko, A. B. Ayusheev, Yu. V. Kharitonov, M. M. Shakirov, and E. E. Shul′ts, Chem. Nat. Compd., 50, 673 (2014).

    Article  CAS  Google Scholar 

  26. P. Xing, Z. Huang, Y. Jin, and B. Jiang, Synthesis, 45, 596 (2013).

    Article  CAS  Google Scholar 

  27. Yu. V. Kharitonov, E. E. Shul′ts, and M. M. Shakirov, Chem. Nat. Compd., 49, 1067 (2013).

    Article  Google Scholar 

  28. L. Westfelt, Acta Chem. Scand., 20, 2829 (1966).

    Article  CAS  Google Scholar 

  29. G. C. Harris and T. F. Sanderson, J. Am. Chem. Soc., 70, 3870 (1948).

    Article  CAS  Google Scholar 

  30. G. M. Sheldrick, SHELX-97 – Programs for Crystal Structure Analysis, Release 97-2, University of Goettingen, Goettingen, Germany.

  31. G. M. Sheldrick, Acta Crystallogr., Sect. C: Struct. Chem., 71, 3 (2015).

  32. A. L. Spek, PLATON, A Multipurpose Crystallographic Tool, version 10M, Utrecht University, The Netherlands, 2003.

    Google Scholar 

  33. A. L. Spek, J. Appl. Crystallogr., 36, 7 (2003).

    Article  CAS  Google Scholar 

Download references

ACKNOWLEDGMENT

The studies were financially supported by the RFBR in the framework of science project No. 19-33-60043. We thank the Khimiya Research Common Use Center, SB, RAS, for performing the spectral and analytical measurements.

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Authors and Affiliations

  1. Novosibirsk State Pedagogical University, 28 Vilyuiskaya St, 630126, Novosibirsk, Russia

    M. A. Gromova

  2. N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, 9 Prosp. Akad. Lavrent’eva, 630090, Novosibirsk, Russia

    Yu. V. Kharitonov, S. A. Borisov, T. V. Rybalova, T. G. Tolstikova & E. E. Shul’ts

Authors
  1. M. A. Gromova
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  2. Yu. V. Kharitonov
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  3. S. A. Borisov
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  4. T. V. Rybalova
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  5. T. G. Tolstikova
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  6. E. E. Shul’ts
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Correspondence to E. E. Shul’ts.

Additional information

For No. 40, see the literature [1].

Translated from Khimiya Prirodnykh Soedinenii, No. 1, January–February, 2022, pp. 51–59.

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Gromova, M.A., Kharitonov, Y.V., Borisov, S.A. et al. Synthetic Transformations of Higher Terpenoids. 41. Synthesis and Anti-Inflammatory Activity of 4-(Carboxyalkyl)-18-nor-isopimara-7,15-Dienes. Chem Nat Compd 58, 55–64 (2022). https://doi.org/10.1007/s10600-022-03596-y

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  • DOI: https://doi.org/10.1007/s10600-022-03596-y

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