Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

[3+2]-Cycloaddition of Nitrile Imines to Parabanic Acid Derivatives – an Approach to Novel Spiroimidazolidinediones

Juliana V. Kuznetsova
ORCID logo ,
Varvara T. Tkachenko
,
Lada M. Petrovskaya
,
Maria E. Filkina
,
Dmitry E. Shybanov
,
Yuri K. Grishin
,
Vitaly A. Roznyatovsky
ORCID logo ,
Viktor A. Tafeenko
,
Anna S. Pestretsova
,
Vera A. Yakovleva
,
Vadim S. Vadim
,
Maxim E. Kukushkin
,
Elena K. Beloglazkina
* ORCID logo
Version 1 : Received: 28 November 2023 / Approved: 28 November 2023 / Online: 28 November 2023 (16:25:22 CET)

A peer-reviewed article of this Preprint also exists.

Kuznetsova, J.V.; Tkachenko, V.T.; Petrovskaya, L.M.; Filkina, M.E.; Shybanov, D.E.; Grishin, Y.K.; Roznyatovsky, V.A.; Tafeenko, V.A.; Pestretsova, A.S.; Yakovleva, V.A.; Pokrovsky, V.S.; Kukushkin, M.E.; Beloglazkina, E.K. [3+2]-Cycloaddition of Nitrile Imines to Parabanic Acid Derivatives—An Approach to Novel Spiroimidazolidinediones. Int. J. Mol. Sci. 2024, 25, 18. Kuznetsova, J.V.; Tkachenko, V.T.; Petrovskaya, L.M.; Filkina, M.E.; Shybanov, D.E.; Grishin, Y.K.; Roznyatovsky, V.A.; Tafeenko, V.A.; Pestretsova, A.S.; Yakovleva, V.A.; Pokrovsky, V.S.; Kukushkin, M.E.; Beloglazkina, E.K. [3+2]-Cycloaddition of Nitrile Imines to Parabanic Acid Derivatives—An Approach to Novel Spiroimidazolidinediones. Int. J. Mol. Sci. 2024, 25, 18.

Abstract

1,3 Dipolar cycloaddition of imidazolidine derivatives containing exocyclic double bonds is a convenient method of creating spiro-conjugated molecules with the promising anticancer active. In this work, the derivatives of parabanic acid (2-thioxoimidazolidine-4,5-diones and 5-aryliminoimidazolidine-2,4-diones) were firstly investigated as dipolarophiles in the reactions with nitrile imines. The generation of nitrile imines was carried out either by the addition of tertiary amine to hydrazonoyl chlorides «drop by drop» or using recently proposed diffusion mixing technique, which led to ~5-15% increasing of target compounds yields. It was found that the addition of nitrile imines to C=S or C=N exocyclic double bonds led to 1,2,4-thiazolines or triazolines and occurred regioselectively in accordance to the ratio of FMO coefficients of reactants. The yield of the resulting spiro-compound depended on the presence of alkyl substituents in nitrile imine structure and was significantly decreases at the reactions with imines with strong electron donor or electron-withdrawing groups. Some of the obtained compounds showed reasonable in vitro cytotoxicity. IC50 values were calculated for HCT116 (colon cancer) cells using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test.

Keywords

parabanic acids; imines; imidazolones, spiro-compounds; 1,3-dipolar cycloaddition; nitrile imines.

Subject

Chemistry and Materials Science, Organic Chemistry

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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