Primidone oxidation catalyzed by metalloporphyrins and Jacobsen catalyst

Primidone (PRM) oxidation by various oxidants such as iodosylbenzene (PhIO), tert-butyl hydroperoxide 70 wt.% (t-BOOH), 3-chloroperoxybenzoic acid (m-CPBA) and hydrogen peroxide 30 wt.%, mediated by either a salen complex or metalloporphyrins, was investigated. The catalytic systems led to phenylethylmalondiamide (PEMA) and phenobarbital (FENO), the same metabolites obtained in vivo with P450 enzymes, although three other products were also detected. Product formation was highly dependent on the oxidant, co-catalyst (imidazole), pH and dioxygen. These biomimetic chemical models have potential application in the synthesis of drug metabolites, which should provide samples for pharmacological tests. They can also be employed in studies that pursue the elucidation of in vivo drug metabolism.

Graphical abstractPrimidone (PRM) oxidation by various oxidants such as iodosylbenzene (PhIO), tert-butyl hydroperoxide 70 wt.% (t-BOOH), 3-chloroperoxybenzoic acid (m-CPBA) and hydrogen peroxide 30 wt.%, mediated by either a salen complex or metalloporphyrins, was investigated. The catalytic systems led to the same metabolites phenylethylmalondiamide (PEMA) and phenobarbital (FENO) obtained in vivo with P450 enzymes, although three other products were also detected.Figure optionsDownload full-size imageDownload as PowerPoint slide