Bacterial infections are on the rise due to the increasing incidence of antibiotic resistance, which poses a serious threat to modern medicine. Successful management of this problem requires international cooperation, a comprehensive approach and the adaptation of strategies in the light of new findings and trends, and above all the monitoring of the occurrence of resistant bacteria and the implementation of measures to prevent their spread. As mortality increases, it is imperative to explore new options in the development of effective antibacterial agents.
In the process of synthesis of an important part of the bacterial cell wall peptidoglycan, the enzyme MurA plays a central role. MurA catalyzes the transfer of enolpyruvate from phosphonolpyruvate (PEP) to UDP-N-acetylglucosamine (UDP-GlcNAc), a key step in the synthesis of the peptidoglycan precursor, UDP-N-acetylmuramic acid. This enzyme is an important target for the development of new antibacterial agents.
The thesis describes the synthesis of glucosamine analogues with modifications at the C1 site. The initial step was the synthesis of the compound, to which the acidic fragments will be attached. A compound was synthesized from acetylated glucosamine chloride by nucleophilic substitution and catalytic hydrogenation, with which I subsequently formed amide bonds with various reagents (acids) by means of coupling reagents at the C-1 site. During the reaction, an amide bond is formed between the primary amino group of the parent compound and the carbonyl group of various diacids, of which one of the carboxylic groups is protected to ensure the reaction proceeds selectively. This is followed by hydrolysis of the acetyl groups and the protective groups. Thus, we synthesized analogues of glucosamine, which form corresponding interactions with the active site of the enzyme MurA.
Finally, glucosamine analogues were analysed by spectroscopic, chromatographic and spectrometric methods.
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