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The effect of substituents on carbon–carbon double bond isomerization in heterocyclic hydrazine derivatives

Chemistry of Heterocyclic Compounds volume 58, pages 206–216 (2022)Cite this article

Even though enehydrazide moiety is present in many pharmaceuticals, there is currently no straightforward method available for preparing cyclic enehydrazides, which could be valuable building blocks in anticancer research. Herein, we report how electronic effects and ring size influence the direction and yield of Ru catalytic carbon–carbon double bond isomerization in heterocyclic enehydrazines. Having the knowledge of how variation of these properties affects the equilibrium between double bond isomers enables us to control the outcome when preparing different cyclic enehydrazides. Six enehydrazide heterocycles and five enehydrazine heterocycles were synthesized and characterized with the current method. In addition, cytotoxicity evaluation of the synthesized compounds showed that several heterocycles produced in this study could be used in developing anticancer drugs.

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Figure 1.
Scheme 1.
Figure 2.
Figure 3.

Notes

  1. In the NMR spectra, asterisk denotes the minor conformer, so far identified.

References

  1. Rollas, S.; Küçükgüzel, S. G. Molecules 2007, 12, 1910.

    Google Scholar 

  2. Schmidt, E. W. Hydrazine and Its Derivatives: Preparation, Properties, Applications; Wiley-Interscience: New York, 2001, 2nd ed.

  3. Lamberth, C.; Dinges, J. In Bioactive Heterocyclic Compound Classes: Agrochemicals; Lamberth, C.; Dinges, J., Eds.; Wiley-VCH: Weinheim, 2012, p. 1.

  4. Blair, L. M.; Sperry, J. J. Nat. Prod. 2013, 76, 794.

    Article  CAS  Google Scholar 

  5. Beveridge, R. E.; Batey, R. A. Org. Lett. 2013, 15, 3086.

    Article  CAS  Google Scholar 

  6. Ueberschaar, N.; Ndejouong, B. L. S. T.; Ding, L.; Maier, A.; Fiebig, H. H.; Hertweck, C. Bioorg. Med. Chem. Lett. 2011, 21, 5839.

    Article  CAS  Google Scholar 

  7. Helaly, S. E.; Pesic, A.; Fiedler, H. P.; Süssmuth, R. D. Org. Lett. 2011, 13, 1052.

    Article  CAS  Google Scholar 

  8. Le Goff, G.; Martin, M.-T.; Servy, C.; Cortial, S.; Lopes, P.; Bialecki, A.; Smadja, J.; Ouazzani, J. J. Nat. Prod. 2012, 75, 915.

    Article  Google Scholar 

  9. Le Goff, G.; Martin, M.-T.; Iorga, B. I.; Adelin, E.; Servy, C.; Cortial, S.; Ouazzani, J. J. Nat. Prod 2013, 76, 142.

    Article  Google Scholar 

  10. Fustero, S.; Sánchez-Roselló, M.; Jiménez, D.; Sanz-Cervera, J. F.; Del Pozo, C.; Aceña, J. L. J. Org. Chem. 2006, 71, 2706.

    Article  CAS  Google Scholar 

  11. Schmidt, B.; Hauke, S.; Mühlenberg, N. Synthesis 2014, 46, 1648.

    Article  Google Scholar 

  12. Halli, J.; Kramer, P.; Bechthold, M.; Manolikakes, G. Adv. Synth. Catal. 2015, 357, 3321.

    Article  CAS  Google Scholar 

  13. Krompiec, S.; Pigulla, M.; Krompiec, M.; Baj, S.; Mrowiec-Białoń, J.; Kasperczyk, J. Tetrahedron Lett. 2004, 45, 5257.

    Article  CAS  Google Scholar 

  14. Ilisson, M.; Tomson, K.; Tamm, T.; Mäeorg, U. Chem. Heterocycl. Compd. 2018, 54, 572.

    Article  CAS  Google Scholar 

  15. Nielsen, S. D.; Ruhland, T.; Rasmussen, L. K. Synlett 2007, 443.

  16. Menchi, G.; Matteoli, U.; Scrivanti, A.; Paganelli, S.; Botteghi, C. J. Organomet. Chem. 1988, 354, 215.

    Article  CAS  Google Scholar 

  17. He, L.; Liang, B.; Huang, Y.; Zhang, T. Natl. Sci. Rev. 2018, 5, 356.

    Article  CAS  Google Scholar 

  18. Smith, J. M.; Lachicotte, R. J.; Holland, P. L. J. Am. Chem. Soc. 2003, 125, 15752.

    Article  CAS  Google Scholar 

  19. Block, J.; Schulz-Ekloff, G. J. Catal. 1973, 30, 327.

    Article  CAS  Google Scholar 

  20. Arisawa, M.; Terada, Y.; Takahashi, K.; Nakagawa, M.; Nishida, A. J. Org. Chem. 2006, 71, 4255.

    Article  CAS  Google Scholar 

  21. Tšupova, S.; Lebedev, O.; Mäeorg, U. Tetrahedron 2012, 68, 1011.

    Article  Google Scholar 

  22. Xu, H.-D.; Jia, Z.-H.; Xu, K.; Han, M.; Jiang, S.-N.; Cao, J.; Wang, J.-C.; Shen, M.-H. Angew. Chem., Int. Ed. 2014, 53, 9284.

    Article  CAS  Google Scholar 

  23. Bredihhin, A.; Mäeorg, U. Tetrahedron 2008, 64, 6788.

    Article  CAS  Google Scholar 

  24. Bredihhin, A.; Groth, U. M.; Mäeorg, U. Org. Lett. 2007, 9, 1097.

    Article  CAS  Google Scholar 

  25. Ilisson, M.; Mäeorg, U. Synth. Commun. 2017, 47, 1231.

    Article  CAS  Google Scholar 

  26. Lavogina, D.; Samuel, K.; Lavrits, A.; Meltsov, A.; Sõritsa, D.; Kadastik, Ü.; Peters, M.; Rinken, A.; Salumets, A. Reprod. Biomed. Online 2019, 39, 556.

    Article  CAS  Google Scholar 

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This research was supported by institutional research funding project IUT20-17 of the Estonian Ministry of Education and the Estonia–Russia Cross Border Cooperation Program (ER30).

The authors would like to thank Lauri Toom for his help with NMR related problems, Lauri Vares for his support and advice, and TBD Biodiscovery for supplying doxorubicin for cytotoxicity measurements.

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Authors and Affiliations

  1. Institute of Chemistry, University of Tartu, 14a Ravila St, 50411, Tartu, Estonia

    Marta-Lisette Pikma, Mihkel Ilisson, Rasmus Zalite, Darja Lavogina, Tõiv Haljasorg & Uno Mäeorg

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  1. Marta-Lisette Pikma
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  2. Mihkel Ilisson
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Correspondence to Marta-Lisette Pikma.

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Published in Khimiya Geterotsiklicheskikh Soedinenii, 2022, 58(4/5), 206–216

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Pikma, ML., Ilisson, M., Zalite, R. et al. The effect of substituents on carbon–carbon double bond isomerization in heterocyclic hydrazine derivatives. Chem Heterocycl Comp 58, 206–216 (2022). https://doi.org/10.1007/s10593-022-03074-x

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