Synthesis of Triazoles with Natural Amino Acid Fragments

The reaction of N-toluenesulfonyl glycine, DL-valine, and DL-leucine hydrazides with isothiocyanates gave substituted thiosemicarbazides containing N-Ts-amino acid fragments, which underwent base-catalyzed cyclization to 3,4-substituted 5-sulfanyl-1,2,4-triazoles. The latter were subjected to alkylation and oxidation to the corresponding 5-hydroxy derivatives. The alkylation with propyl bromide, chloroacetamide, and 5-acetyl-2-methoxybenzyl chloride involved both sulfur and nitrogen nucleophilic centers of the triazole derivatives containing a glycine residue and only the sulfur atom of valine and leucine analogues. The synthesized compounds were screened for antibacterial and anti-monoamine oxidase activities, and docking analysis against relevant protein targets was performed.