Scientists from St. Petersburg State University have synthesized two types of new compounds with antibacterial properties. In the future, according to the results of the study, an affordable alternative to the antibiotics widely used today, to which pathogens have already acquired resistance, may appear. It was possible to obtain new substances thanks to just one reaction, changing only its conditions. In one case, the transformation was initiated by gold, and in the second by blue light.
As a basis for the synthesis of a number of biologically active compounds, diazoesters are used today ― organic molecules having two nitrogen atoms connected to each other, as well as an ester group. But so far, the reactions of diazoesters have been well studied only with fairly simple substances, such as alcohols and carboxylic acids. In order to obtain new molecules potentially capable of becoming drugs, in particular effective antibiotics, it is necessary to study the interaction of diazoesters with more complex "partners".
In the first experiment, scientists from St. Petersburg State University conducted reactions between diazoesters and nitrogen-containing cyclic carboxylic acids by adding a gold-based catalyst to the solution of the starting substances. As a result, oxazinone molecules were formed, whose derivatives have antibacterial properties. This method turned out to be universal: it can be used to obtain a wide variety of oxazinones, and besides, it is simpler, since it does not require long multistage reactions with a large number of different reagents.
Blue light acted as the initiator of the second reaction with the same initial compounds. As a result, previously unknown products were obtained — azirin-2-carboxylic esters, the properties of which will have to be investigated in the future.
"So far, this study is only the "first swallow". It is necessary to study the cytotoxic activity of these substances and obtain their new derivatives. It should be understood that the direct use of these substances is still far away. The future prospects of this project may be connected with light. To initiate the reaction, we can use blue light ― this is one of the components of visible light. We see our future in developing and exploring reactions that are initiated not even by blue light, but by visible light. This is very promising from the point of view of ecology: we do not clog the substance with heavy metals, which, in fact, is gold. When working with light, we do not add anything superfluous to the connections. Our efforts will be focused in this direction," said Nikolay Rostovsky, Associate Professor of the Department of Organic Chemistry of St. Petersburg State University, Doctor of Chemical Sciences.
After studies of the synthesized compounds, it turned out that some oxazinones obtained by the authors effectively inhibit the growth of Enterococcus faecium and Staphylococcus aureus bacteria: these microorganisms are highly resistant to antibiotics and cause wound infections, urinary tract and intestinal infections.
"We have shown that by changing the reaction conditions, that is, directing it with the help of a catalyst or light, it is possible to obtain various products that can potentially have properties valuable for medicine. So, thanks to the approach we have proposed, oxazinones can become a more affordable alternative to antibiotics widely used today, to which bacteria are increasingly becoming resistant," commented Nikolai Rostovsky.
The results of the study, supported by grants from the Russian Science Foundation (RNF), are published in the journal Organic Letters.
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