1,3-Dipolar Cycloaddition of Nitrile Oxides and Nitrilimines to (-)-β-Caryophyllene: Stereoselective Synthesis of Polycyclic Derivatives and Their Biological Testing.

Autor: Shybanov DE; Department of Chemistry, M. V. Lomonosov Moscow State University, 119991 Moscow, Russia., Kukushkin ME; Department of Chemistry, M. V. Lomonosov Moscow State University, 119991 Moscow, Russia., Grishin YK; Department of Chemistry, M. V. Lomonosov Moscow State University, 119991 Moscow, Russia., Roznyatovsky VA; Department of Chemistry, M. V. Lomonosov Moscow State University, 119991 Moscow, Russia., Tafeenko VA; Department of Chemistry, M. V. Lomonosov Moscow State University, 119991 Moscow, Russia., Abo Qoura L; Research Institute of Molecular and Cellular Medicine, People's Friendship University of Russia (RUDN University), 117198 Moscow, Russia.; N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russian Federation, 115478 Moscow, Russia., Pokrovsky VS; Research Institute of Molecular and Cellular Medicine, People's Friendship University of Russia (RUDN University), 117198 Moscow, Russia.; N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russian Federation, 115478 Moscow, Russia., Yarovaya OI; N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Lavrentjev Avenue 9, 630090 Novosibirsk, Russia., Belyaevskaya SV; Pasteur Research Institute of Epidemiology and Microbiology, 14 MiraStr, 197101 St. Petersburg, Russia., Volobueva AS; Pasteur Research Institute of Epidemiology and Microbiology, 14 MiraStr, 197101 St. Petersburg, Russia., Esaulkova IL; Pasteur Research Institute of Epidemiology and Microbiology, 14 MiraStr, 197101 St. Petersburg, Russia., Zarubaev VV; Pasteur Research Institute of Epidemiology and Microbiology, 14 MiraStr, 197101 St. Petersburg, Russia., Beloglazkina EK; Department of Chemistry, M. V. Lomonosov Moscow State University, 119991 Moscow, Russia.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2024 Oct 24; Vol. 25 (21). Date of Electronic Publication: 2024 Oct 24.
DOI: 10.3390/ijms252111435
Abstrakt: The cycloaddition of nitrile oxides and nitrilimines to one or both of the C=C double bonds of caryophyllene is described. The possibility of introducing five-membered fused and spiro-linked heterocycles into the structure of sesquiterpenes by the 1,3-dipolar cycloaddition reactions of nitrile oxides and nitrilimines to caryophyllene was demonstrated. As a result of these reactions, pharmacophore fragments of isoxazoline and pyrazoline are introduced into the structure of caryophyllene, which leads to an increase in the conformational rigidity of the molecule. A complete stereochemical assignment of 1,3-dipolar cycloaddition adducts to caryophyllene was carried out. The study of antiviral and cytotoxic activity for some heterocyclic derivatives synthesized in this work revealed relatively high biological activity of previously little-studied cycloaddition adducts at the exocyclic C=CH 2 bond of caryophyllene. The effect of substituents in the synthesized heterocycles on biological activity was demonstrated. Compounds with a good inhibitory effect on the H1N1 influenza virus were revealed. The activity of the compound was demonstrated up to 6 h post infection, and this could be due to slight inhibiting activity against viral neuraminidase, necessary at the stage of progeny virion budding.
Databáze: MEDLINE
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