| Abstract [eng] |
Over the past several decades, bioactive peptides have been attracting scientific interest due to their ability to interact with receptors or inhibit protein–protein interactions. However, most peptides are denoted by low lipophilicity, high molecular weights and charged functional groups; as a result, they are unable to cross the intestinal epithelial barrier. For these reasons, in order to improve the properties of the native peptides, such as their biological activity and metabolic stability, unnatural amino acids (UAAs) are usually used as rigidifying elements. An effective method for convenient synthesis of new amino acid-like building blocks from easily accessible starting materials has been developed. 5-[1-(tert-Butoxycarbonyl)azetidin-3-yl]-1H-pyrazole-3-carboxylate was easily N-alkylated with various types of alkyl halogenides with the objective to obtain two separable regioisomers suitable for the building-block library. Easily accessible N-Boc-3-iodoazetidine was used as the N-alkylating agent in the reaction with commercially available pyrazole and indazole carboxylates so that to extend the variety of synthetic amino acids. Pyrazole and the piperidine ring were easily connected by the N-alkylation reaction with mesylate activated nucleophile. Pyrazolo[4,3-c]pyridine was easily N-alkylated with various types of alkyl halogenides to obtain two separable regioisomers suitable for the building-block library. The carbonyl group of two selected indole-3-acetic acids was transformed into a 1,3,4-oxadiazole ring. The prepared 1,3,4-oxadiazoles possess antioxidant properties at low concentrations. |
