Simplified the Production of Important Medicinal Molecules

Researchers at the S.P. Korshunov Research Laboratory No. 13 "Organic Synthesis and Analysis" at TSU worked with complex organic molecules with multiple active sites for chemical transformations. The second key component was hydrazine, a highly active reagent containing nitrogen. The scientists found that by simply varying the proportions of the starting materials, they can precisely control which useful chemical compounds are produced.

"If the components are mixed in a 1:1 ratio, the reaction proceeds along the first pathway, resulting in the formation of so-called pyrazolines cyclic molecules highly sought after in pharmacology. The yield of the useful product reaches 92%," explains TSU Professor Alexander Golovanov. "If significantly more hydrazine is added, the reaction switches to the second pathway, producing other valuable compounds–pyrazoles (yield 79-84%). The work was essentially carried out by my graduate student, Evgeny Zatynatsky. The research was conducted in collaboration with the Ufa Institute of Chemistry and Professor Stanislav Grabovsky."

Previously, pyrazoles were obtained using the classical method, that is, by mixing organic compounds with hydrazine. However, this approach was not ideal: often, instead of a single desired substance, a mixture of similar products formed, which were very difficult to separate. Many reactions had to be carried out at high temperatures, over long periods, or using aggressive chemicals. But the main problem was the method's lack of flexibility. In particular, it was poorly suited for creating complex molecules with desired properties, as it did not allow for the easy addition of specific fragments essential for biological activity at the desired locations within the molecule.

It was precisely these limitations that the new approach developed at TSU helped overcome. Chemists not only observed the results but also thoroughly studied the process mechanism using modern analytical methods, including nuclear magnetic resonance spectroscopy and X-ray diffraction analysis. They experimentally demonstrated that pyrazoles and pyrazolines are formed in parallel, rather than being converted into each other, making the method particularly pure and effective.

"The most valuable thing is that we were able to obtain pure pyrazolines in their original form," says Evgeny Zatynatsky. "Previously, their synthesis was practically impossible. These molecules are very 'capricious': they have a particularly active site–the nitrogen atom–which easily reacts even with air and can degrade the substance. Therefore, to study them, chemists had to temporarily 'protect' them. Under the right conditions, this active site of pyrazoline remains accessible for the attachment of other moieties, which is crucial for the creation of new compounds and, consequently, for the development of new, more effective drugs."

The scientists presented the results of their study in a paper published in Tetrahedron, a prestigious international scientific journal that publishes articles on organic chemistry and its applications in related disciplines.