PROCEEDINGS OF THE SHEVCHENKO SCIENTIFIC SOCIETY

Chemical Sciences

Archive / Volume LXXIII 2023

Nataliia SLYVKA1, Lesya SALIYEVA1, Mariia LITVINCHUK2, Mykhailo VOVK2

1Lesya Ukrainka Volyn National University, 13, Voli Ave., Lutsk 43025, Ukraine
e-mail: slivka.natalia@vnu.edu.ua

2Institute of Organic Chemistry of the NAS of Ukraine, 5, Murmanska Str., 02660 Kyiv, Ukraine

DOI: https://doi.org/10.37827/ntsh.chem.2023.73.079

REACTION OF [3+2]-CYCLOADDITION IN THE SYNTHESIS OF NEW (BENZ)IMIDAZO[2,1-b][1,3]THIAZINYL-1,6a-DIHYDROPYRROLO[3,4-d][1,2,3]TRIAZOLE-4,6(3aH,5H)-DIONES

1,2,3-Triazoles, due to their unique chemical and physical properties, have found wide application in organic, medical and pharmaceutical chemistry, agrochemistry and materials chemistry. Functionalized 1,2,3-triazoles, built on the basis of positional substitutions, are characterized by a wide spectrum of biological activity. Equally important for the design of potential drug-like molecules is the imidazo[2,1-b]thiazine condensed cycle, which is the basis of many drugs and compounds with diverse biological activity. Therefore, the combination of these scaffolds in the structure of one molecule seems quite attractive from a chemical and biological point of view. Synthetically available azido(benzo)imidazo[2,1-b][1,3]thiazines, the method of synthesis of which was described in our previous work, were used as basic substrates to obtain previously unknown hybrid compounds 1-{(benz)imidazo[2,1-b]thiazinyl}-1,6a-dihydropyrrolo[3,4-d][1,2,3]triazole-4,6 (3aH,5H)-diones. It was established that the [3+2]-cycloaddition of azides to N-arylmaleinimides during boiling in benzene for 24 h, i.e. under the conditions of the Huisgen reaction, proceeds smoothly and leads to hybrid structures in which the imidazothiazine ring is connected to the pyrrolotriazole nucleus. Composition and structure of synthesized 1-{(benz)imidazo[2,1-b]thiazinyl}-1,6a-dihydropyrrolo[3,4-d][1,2,3]triazole-4,6(3aH,5H)-diones are unambiguously confirmed by the data of physicо-chemical analysis, in particular, chromatography-mass spectrometry, as well as data of elemental analysis. Analysis of 1Н and 13C NMR spectra of the synthesized compounds is characterized by a doubling of the signals of all protons and carbon atoms, which is evidence of their existence in the form of a diastereomeric mixture.
Thus, [3+2]-cycloaddition of azido(benzo)imidazo[2,1-b][1,3]thiazines 1a-c with substituted N-phenyl-maleinimides 2a-d turned out to be an effective approach for obtaining previously unknown 1-{(benz)imidazo¬[2,1-b]thiazinyl}-1,6a-dihydropyrrolo[3,4-d][1,2,3]triazole-4,6(3aH,5H)-diones 3a-e. The proposed synthesis method enables satisfactory yields to obtain target products, which are promising objects for further research into their biological activity.

Keywords: azido(benzo)imidazo[2,1-b][1,3]thiazines; [3+2]-cycloaddition; N-arylmaleinimides; 1-{(benz) imidazo[2,1-b]thiazinyl}-1,6a-dihydropyrrolo[3,4-d][1,2,3]triazole-4,6(3aH,5H)-diones.

References:

    1. Tam A., Arnold U., Soellner M.B., Raines R.T. Protein prosthesis: 1,5-disubstituted[1,2,3]-triazoles as cis-peptide bond surrogates. J. Am. Chem. Soc. 2007. Vol. 129. P. 12670–12671. (https://doi.org/10.1021/ja075865s).
    2. Huo J., Hu H., Zhang M., Hu X., Chen M., Chen D., Liu J., Xiao G., Wang Y., Wen Z. A mini review of the synthesis of poly-1,2,3-triazole-based functional materials. RSC Adv. 2017. Vol. 7. P. 2281–2287. (https://doi.org/10.1039/C6RA27012C).
    3. Agalave S.G., Maujan S.R., Pore V.S. Click Chemistry: 1,2,3-Triazoles as Pharmacophores. Chem. Asian J. 2011. Vol. 6. P. 2696–2718. (https://doi.org/10.1002/asia.201100432).
    4. Xu Z., Zhao S.J., Liu Y. 1,2,3-Triazole-containing hybrids as potential anticancer agents: Current developments, action mechanisms and structure-activity relationships. Eur. J. Med. Chem. 2019. Vol. 183. e111700. (https://doi.org/10.1016/j.ejmech.2019.111700).
    5. Jiang X., Hao X., Jing L., Wu G., Kang D., Liu X., Zhan P. Recent applications of click chemistry in drug discovery. Expert Opin. Drug Discov. 2019. Vol. 14. P. 779. (https://doi.org/10.1080/17460441.2019.1614910).
    6. Chu X.M., Wang C., Wang W.L., Liang L.L., Liu W., Gong K.K., Sun K.L. Triazole derivatives and their antiplasmodial and antimalarial activities. Eur. J. Med. Chem. 2019. Vol. 166. P. 206. (https://doi.org/10.1016/j.ejmech.2019.01.047).
    7. Gao P., Sun L., Zhou J., Zhan X.Li.P., Lin X. Discovery of novel anti-HIV agents via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry-based approach. Expert Opin. Drug Discov. 2016. Vol. 11. P. 857. (https://doi.org/10.1080/17460441.2016.1210125).
    8. Assis S.P.O., Silva M.T., Oliveira R.N., Lima V.L. Synthesis and anti-inflammatory activity of new alkyl-substituted phthalimide 1H-1,2,3-triazole derivatives. Scientific World J. Vol. 2012. P. 1–7. (https://doi.org/10.1100.2012.925925).
    9. Zhang S., Xu Z., Gao C., Ren Q.C., Chang L., Lv Z.S., Feng L.S. Triazole derivatives and their anti-tubercular activity. Eur. J. Med. Chem. 2017. Vol. 138. P. 501. (https://doi.org/10.1016/j.ejmech.2017.06.051).
    10. Wang X.-L., Wan K., Zhou C.-H. Synthesis of novel sulfanilamide-derived 1,2,3-triazoles and their evaluation for antibacterial and antifungal activities. Eur. J. Med. Chem. 2010. Vol. 45. P. 4631–4639. (https://doi.org/10.1016/j.ejmech.2010.07.031).
    11. Agard N.J., Preschner J.A., Bertozzi C.R. A Strain-Promoted [3+2] Azide−Alkyne Cycloaddition for Covalent Modification of Biomolecules in Living Systems. J. Am. Chem. Soc. 2004. Vol. 126. P. 15046–15047. (https://doi.org/10.1021/ja044996f).
    12. Agard N.J., Baskin J.M., Prescher J.A., Lo A., Bertozzi C.R. A Comparative Study of Bioorthogonal Reactions with Azides. ACS Chem. Biol. 2006. Vol. 1. P. 644–648. (https://doi.org/10.1021/cb6003228).
    13. Ferreira V.F., da Rocha D.R., da Silva F.C., Ferreira P.G., Boechat N.A., Magalhães J.L. Novel 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole derivatives: a patent review (2008–2011). Expert Opin. Ther. Pat. 2013. Vol. 23. P. 319–331. (https://doi.org/10.1517.13543776.2013.749862).
    14. Mandal S.K., Saha D., Debajyoti M., Jain V.K. Sythesis and antitubercular activity of some triazole derivatives of propyl gallate. Int. J. Pharm. Sci. Res. 2010. Vol. 1. P. 465–472. (ISSN: 0975-9492).
    15. Dunn G.L., Hoover J.R., Berges D.A., Taggart J.J., Davis L.D., Dietz E.M., Jakas N., Yim P., Actor J.V., Weisbach J.A. Orally active 7-phenylglycyl cephalosporins. Structure-activity studies related to cefatrizine (SK&F 60771). J. Antibiot. 1976. Vol. 29(1). P. 65–80. (https://doi.org/10.7164/antibiotics.29.65).
    16. Pearson M., Garcia-Ecbeverria C., Fabbro D. Protein Tyrosine Kinases as Targets for Cancer and Other Indications. 2006. P. 1–29. (https://doi.org/10.1385/1-59259-962-1:001).
    17. Schoeder C.T., Kaleta M., Mahardhika A.B., Olejarz-Maciej A., Łażewska D., Kieć-Kononowicz K., Müller C.E. Structure-activity relationships of imidazothiazinones and analogs as antagonists of the cannabinoid-activated orphan G protein-coupled receptor GPR18. Eur. J. Med. Chem. 2018. Vol. 155. P. 381–397. (https://doi.org/10.1016/j.ejmech.2018.05.050).
    18. Gong J.-X., Cui Y., He Z.-L., Guo Y.-W. Synthesis, spectral characterization, and antituberculosis activity of thiazino[3,2-а]benzimidazole derivatives. Phosphorus, Sulfur, Silicon. 2016. Vol. 191(7). P. 1036–1041. (https://doi.org/10.1080/10426507.2015.1135149).
    19. Thompson A.M., O’Connor P.D., Marshall A.J., Francisco A.F., Kelly J.M., Riley J., Read K.D., Perez C.J., Cornwall S., Thompson R.C.A., Keenan M., White K.L., Charman S.A., Zulfiqar B., Sykes M.L., Avery V.M., Chatelain E., Denny W.A. Re-evaluating pretomanid analogues for Chagas disease: Hit-to-lead studies reveal both in vitro and in vivo trypanocidal efficacy. Eur. J. Med. Chem. 2020. Vol. 207. P. 112849. (https://doi.org/10.1016/j.ejmech.2020.112849).
    20. Saliyeva L., Slyvka N., Holota S., Grozav A., Yakovychuk N., Litvinchuk M., Vovk M. Synthesis and evaluation of bioactivity of 6-[(2-pyridinyloxy)](benzo)imidazo[2,1-b][1,3]thiazines. Biointerface Research in Applied Chemistry. 2022. Vol. 12(4). P. 5031–5044. (https://doi.org/10.33263/BRIAC124.50315044).
    21. Slyvka N., Saliyeva L., Litvinchuk M., Shishkina S., Vovk M. Features of interaction (benzo)imidazo[2,1-b][1,3]thiazine mezylates with nucleophilic reagents. Chem. Chem. Technol. ID: 673/19.01.23.
    22. Dürüst Y., Karakuş H., Kaiser M., Tasdemir D. Synthesis and anti-protozoal activity of novel dihydropyrrolo[3,4-d][1,2,3]triazoles. Eur. J. Med. Chem. 2012. Vol. 48. P. 296–304. (https://doi.org/10.1016/j.ejmech.2011.12.028).

How to Cite

SLYVKA N., SALIYEVA L., LITVINCHUK M., VOVK M. REACTION OF [3+2]-CYCLOADDITION IN THE SYNTHESIS OF NEW (BENZ)IMIDAZO[2,1-b][1,3]THIAZINYL-1,6a-DIHYDROPYRROLO[3,4-d][1,2,3]TRIAZOLE-4,6(3aH,5H)-DIONES. Proc. Shevchenko Sci. Soc. Chem. Sci. 2023. Vol. LXXIII. P. 79-85.

Download the pdf