Metabolites of methyl 5(6)-butyl-2-benzimidazolecarbamate (parbendazole). Structure and synthesis

Abstract

The structures of seven metabolites (II-VIII) of the potent anthelminthic methyl 5(6)-butyl-2-benzimidazolecarbamate (I) isolated from sheep and cattle and from two fungi were determined, largely by physical methods. Six were products of side-chain oxidation, and one was an aromatic-ring hydroxylation product. The two major metabolites isolated from both sheep and cattle were shown to be the carboxylic acid II and the 1,2-diol III. The structures of all metabolites were confirmed by synthesis, and the configuration of diol metabolite III was shown to be predominantly three by synthesis via a stereospecific route.

Identification of biliary metabolites of Mebendazole in the rat

“…It is a minor metabolic route for parbendazole in cattle (15) and in sheep (16). No evidence of aromatic ring hydroxylation could be found for mebendazole in this study.…”

Metabolic and tissue residue studies on parbendazole in sheep

“…Structures for each of the urinary metabolites were determined utilizing ultraviolet, infrared, proton magnetic resonance, and mass spectrometric techniques. Confirmation of these structures was achieved by chemical synthesis as reported by Dunn et al (1973). Results of the analytical studies are presented in Table . The metabolic transformation of parbendazole-14C in sheep was postulated to occur as described in Figure 5.…”

Microbial Transformation of Methyl 5(6)-Butyl-2-Benzimidazolecarbamate

“…an authentic sample (3). No effort was made to quantitate or recover the remaining II or III from the pH 9.0 chloroform extract.…”

“…Soc. 1968) and confirmation of structure of the animal and microbial metabolites (3) have been described previously. The present paper describes the microbial transformation studies, the isolation of two of the metabolites, and a proposed microbial transformation pathway.…”