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Oleg Nikolaevich Burov 

Associate Professor

Faculty of Chemistry

E-mail:
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Degree: Candidate of Sciences

Personal page in Russian:
https://sfedu.ru/person/onburov
Personal page in English:
https://sfedu.ru/en/person/onburov

Research interests:

Chemistry of Berberine,

Chemical Calculations,

DFT Calculations,

Density Functional Theory,

Nitric donators, 

Knoevenagel Condensation,

Organic Synthesis,

NMR Spectroscopy

Research projects:

In the course of scientific research on the creation of biologically active systems, complex work was carried out on the basis of alkaloid berberine to study the ways of its modification and the fundamental regularities underlying the action of its derivatives.

Thus, in studying of nucleophilic pathways of the berberine modification, amination processes were studied in detail. There were significant differences in the behavior of primary and secondary amines with berberine. In addition, the principle role of the solvent as a direct participant in the processes of nucleophilic substitution in berberine was demonstrated using quantum chemical calculations and experimentally. Obtaining 9-N-substituted berberines having no proton at the nitrogen atom of the amino group has been shown to be principally impossible, and selective demethylation of berberine was observed under the action of secondary amines. A technique for obtaining berberrubine with a yield of up to 60% has been developed, and it shown clear advantage over the methods described in the literature, since it does not require a deep vacuum and a long, multi-stage purification of the product. The method allowing aminating the 9-position of the berberine system with physiologically active amines, including those containing pyrrole fragments, unsubstituted on the nitrogen atom, has been improved. The developed methods and revealed regularities made it possible to obtain berberrubine and amine derivatives of berberine as promising scaffolds for further modification.

The method of 13-nitroaryl derivatives synthesis for reduced forms of berberine (8-acetonylberberine and dihydroberberine) in one-pot interaction of reduced berberines and neutral aromatic electrophilic compounds (picryl chloride, 4-chloro-7-nitrobenzofurazan, 4-chloro-5,7-dinitrobenzofurazan and 4-chloro-5,7-dinitrobenzofuroxan) first developed when studying the ways of the electrophilic modification of berberine. 13-Nitroaryl derivatives obtained are characterized by a zwitterionic structure, and the degree of charge transfer, calculated in the approximations of the density functional theory (DFT) in the B3LYP/6-31G(d, p) basis set, increases with the electrophilicity of nitroarene. The synthesized 13-substituted berberine derivatives, according to the results of molecular docking, showed a significant affinity for G-quadruplexes (inhibition constant pKi is ~ 4-8), which makes these compounds promising drugs for the treatment of a wide range of oncological diseases.

To reveal the mechanisms of the biological effect of nitroarenes introduced into berberine as endogenous nitrogen oxide (NO) sources, the mechanisms of thiol-induced destruction of unsubstituted and annelated furoxans were studied using quantum chemical calculations within the DFT in the 6-311++G(d, p) basis set to form nitric oxide. For all systems, the preferrability of NO production by the radical mechanism of attack of the sulfanyl HS-radical   on the carbon atom bonded to the N-oxide group is shown. Also it was shown that ionic mechanisms involving HS-anions are in all cases unrealizable because of their high endothermicity. The calculated results showed that experimentally fixed high NO donor activity of aryl derivatives of dinitrobenzofuroxan can be related to the existence of N-oxide tautomerism, and 3-N-oxide is more reactive towards sulfanyl radical.

Thus, synthetic methods of electrophilic and nucleophilic modification of berberine alkaloid have been developed, the regularities of their structure have been studied, and the main ways of their use have been proposed together with the mechanisms of biological action.

Teaching:

  • Organic chemistry
  • Base of natural science
  • Chemistry of hight molecular compounds