Synthesis of new compounds derived from metronidazole and amino acids and their esters as antiparasitic agents

Abstract

A number of new compounds derived from metronidazole and amino acids and their esters have been synthesized through a reaction between 2-(2-methyl-5-nitro-1H-imidazol-1-yl)acetic acid and a number of amino acid esters in the presence of N,N 0 carbonyldiimidazole (CDI). Hydrolysis of the esters derivatives with sodium hydroxide (4%) followed by acidification with hydrochloric acid (3 M) afforded the corresponding acids. The newly synthesized compounds were characterized by elemental analysis and by spectroscopic techniques such as 1 H-NMR, 13 C-NMR, and mass spectrometry. Some of the prepared compounds exhibited lethal activity against pathogenic protozoan parasites.

Preparation and biological evaluation of metronidazole derivatives with monoterpenes and eugenol

“…The first series consisted of ester conjugates and was prepared by reacting the metronidazole oxidized to acetic acid and monoterpenes and eugenol using DCC according to procedures reported in the literature (Scheme 1). The synthesised compounds were confirmed by FTIR, NMR, and MS. Infrared spectra showed the characteristics band of C=O stretching in range of 1,750–1,800 cm −1 , C‐O stretching in range of 1,200–1,280 cm −1 , and disappearance of OH stretching, which confirms the formation of the ester. The H 1 NMR spectra showed characteristic chemical shift, and mass spectra showed the parent peak which anticipated the structure of compounds.…”

“…Metronidazole conjugates were prepared in two different series. The first series key reagent metronidazole carboxylic acid was obtained from the oxidation of the commercially available metronidazole employing potassium dichromate, as shown in Scheme 1 . Metronidazole carboxylic acid was then reacted with selected monoterpenes (menthol, thymol, and carvacrol) and the phenylpropanoid eugenol; the reaction was completed using DCC/DMAP …”

“…The synthesis of compound ( 2 ) was achieved using a reported method with slight modification . In a stirring suspension of metronidazole (3.42 g, 20 mM) in 10 ml, H 2 O at room temperature, (4.36 g 15 mM) of potassium dichromate in 10 ml H 2 O was added followed by dropwise addition of 5 ml sulfuric acid 50% in ice water.…”