Synthesis and physical-chemical properties of 3-benzyl-8-propylxanthinyl-7-acetic acid and its derivatives

Authors

  • E. K. Mikhalchenko Zaporizhzhia State Medical University,
  • K. V. Аleksandrova Zaporizhzhia State Medical University,
  • S. V. Levich Zaporizhzhia State Medical University,
  • D. M. Sinchenko Zaporizhzhia State Medical University,

DOI:

https://doi.org/10.14739/2409-2932.2017.1.93430

Keywords:

xanthines, organic synthesis, NMR-spectroscopy

Abstract

Introduction. Heterocyclic compounds play an important role in the metabolic processes of human organism. Structures of vitamins, nucleotides, chromoproteins are based on Nitrogen-containing heterocycles (purine, pyrimidine, thiazole etc). Thus, it was obvious to use these organic substances as basic molecules for synthetic research of biologically active compounds which could be used for treatment of different pathological processes. In their research, some scientist pay special attention to xanthine derivatives that are well-known low toxic natural compounds with wide spectrum of pronounced pharmacological properties (antioxidant, diuretic, antibacterial, anti-inflammatory etc). Insertion of carboxyl group in the structure of xanthine molecule is a prospective ability of its synthetic potential increasing.

Aim of our research was the development of method of 3-benzyl-8-propylxanthinyl-7-acetic acid and its derivatives synthesis and studying their physical-chemical properties.

Materials and methods. Melting points were determined using capillary method on DMP (M). 1Н NMR-spectra were recorded by Varian Mercury VX-200 device (company «Varian», USA) solvent – (DMSO-d6), internal standard – ТМS. Elemental analysis of obtained compounds was produced on device Elementar Vario L cube.

Results and discussion. We selected 3-benzyl-8-propyl xanthine as initial compound for our study. By its interaction with chloroacetic acid, chloroacetamide or propyl chloroacetate in DMF in the presence of calculated amount of NaHCO3 we synthesized 3-benzyl-8-propylxanthinyl-7-acetic acid its ester and amide. At the same time we found that obtaining of xanthinyl-7-acetic acid by hydrolysis of its ester produced with higher yield. On the next stage of our research we synthesized a number of water-soluble salts of 3-benzyl-8-propylxanthinyl-7-acetic acid by reaction of acid with different primary and secondary amines. The structures of all obtained compounds were proved by the elemental analysis and 1H NMR-spectroscopy.

Conclusions. Obtained results of our work can be used for further search of biologically active compounds among xanthine derivatives with carboxyl residue.

References

Lieberman, M., Marks, A., & Smith, C. (2007) Marks' Essential Medical Biochemistry. Lippincott Williams & Wilkins.

Joule, J. A., & Mills, K. (2012) Heterocycles in Nature. Heterocyclic Chemistry at a Glance (2nd ed). (P. 158–166). Chichester: John Wiley & Sons, Ltd.

Joule, J. A., & Mills K. (2012) Heterocycles in Medicine. Heterocyclic Chemistry at a Glance (2nd ed). (P. 167–179).Chichester: John Wiley & Sons, Ltd.

Müller, C. E., Sandoval-Ramírez, J., Schobert, U., Geis, U., Frobenius, W., & Klotz, K. N. (1998) 8-(Sulfostyryl)xanthines: water-soluble A2A-selective adenosine receptor antagonists. Bioorganic & Medicinal Chemistry, 6, 707–719. doi: 10.1016/S0968-0896(98)00025-X.

Mohamed, T., Osman, W., Tin, G., & Rao, P. N. (2013) Selective inhibition of human acetylcholinesterase by xanthine derivatives: In vitro inhibition and molecular modeling investigations. Bioorganic & Medicinal Chemistry Letters, 23, 4336–4341. doi: 10.1016/j.bmcl.2013.05.092.

Mak, G., & Hanania, N. A. (2012) New bronchodilators. Curr. Op. Pharmacol, 12, 238–245.

Song, B., Xiao, T., Qi, X., Li, L. N., Qin, K., Nian, S., et al. (2012) Design and synthesis of 8-substituted benzamido-phenylxanthine derivatives as MAO-B inhibitors. Bioorganic & Medicinal Chemistry Letters, 22, 1739–1742. doi: 10.1016/j.bmcl.2011.12.094.

Yadav, R., Bansal, R., Rojilla, S., Kachler, S., & Klotz, K. N. (2016) Synthesis and pharmacological characterization of novel xanthine carboxylate amides as A2A adenosine receptor ligands exhibiting bronchospasmolytic activity. Bioorganic Chemistry, 65, 26–37. doi: 10.1016/j.bioorg.2016.01.003.

Lupascu, F. G., Dash, M., Samal, S. K., Dubruel, P., Lupusoru, C. E., Lupusoru, R. V., et al. (2015) Development, optimization and biological evaluation of chitosan scaffold formulations of new xanthine derivatives for treatment of type-2 diabetes mellitus. European Journal of Pharmaceutical Sciences, 77, 122–134. doi.org/10.1016/j.ejps.2015.06.008.

Mikhal’chenko, Ye. K., Aleksandrova, K. V., & Levich, S. V. (2016) Syntez i fizyko-khimichni vlastyvosti 3-benzyl-8-propilksantynu ta yoho vodorozchynnykh solei [Synthesis and physical-chemical properties of 3-benzyl-8-propylxanthine and its water-soluble salts]. Current issues in pharmacy and medicine: science and practice, 1, 26–30. doi: 10.14739/2409-2932.2016.1.62005. [in Ukrainian].

Aleksandrova, E. V., Levich, S. V., Romanenko, N. I., Shkoda, A. S., & Mikhalchenko, E. K. (2014) Synthesis, transformations, and physicochemical properties of 3-(4’-methylphenyl)-8-methylxanthine derivatives. Chem. Nat. Comp., 49(6), 1105–1109. doi: 10.1007/s10600-014-0830-2.

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How to Cite

1.
Mikhalchenko EK, Аleksandrova KV, Levich SV, Sinchenko DM. Synthesis and physical-chemical properties of 3-benzyl-8-propylxanthinyl-7-acetic acid and its derivatives. Current issues in pharmacy and medicine: science and practice [Internet]. 2017Feb.20 [cited 2024Jul.21];(1). Available from: http://pharmed.zsmu.edu.ua/article/view/93430

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Synthesis of the biologically active compounds