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Cytidine deaminases (CDAs) catalyze the hydrolytic deamination of cytidine and 2′-deoxycytidine to uridine and 2′-deoxyuridine. Here, we report that prokaryotic homo-tetrameric CDAs catalyze the nucleophilic substitution at the fourth position of N 4 -acyl-cytidines, N 4 -alkyl-cytidines, and N 4 -alkyloxycarbonyl-cytidines, and S 4 -alkylthio-uridines and O 4 -alkyl-uridines, converting them to uridine and corresponding amide, amine, carbamate, thiol, or alcohol as leaving groups. The x-ray structure of a metagenomic CDA_F14 and the molecular modeling of the CDAs used in this study show a relationship between the bulkiness of a leaving group and the volume of the binding pocket, which is partly determined by the flexible β3α3 loop of CDAs. We propose that CDAs that are active toward a wide range of substrates participate in salvage and/or catabolism of variously modified pyrimidine nucleosides. This identified promiscuity of CDAs expands the knowledge about the cellular turnover of cytidine derivatives, including the pharmacokinetics of pyrimidine-based prodrugs.

A convenient synthetic route for preparation of 5-hydroxyomeprazole (metabolite of omeprazole) was developed. During this work synthetic possibilities to attain the crucial precursor -[6-(chloromethyl)-4-methoxy-5-methylpyridin-3-yl]methanol -were studied and evaluated.

A convenient synthetic route for preparation of valuable synthetic intermediates -1-(1-ethoxyethyl)-3-iodo-1H-pyrazole derivatives has been developed. During this work protection reaction of N-H bond in substituted 3-iodo-1H-pyrazole derivatives with ethyl vinyl ether and migration of ethoxyethyl protecting group was investigated. Synthetic possibilities of Sonogashira cross-coupling reactions of substituted 1-(1-ethoxyethyl)-3-iodo-1H-pyrazole derivatives with phenylacetylene were studied and evaluated.