N-Demethylation and N-oxidation of thebaine, an isoquinoline alkaloid by Mucor piriformis

Northebaine was identified as the major metabolite formed during the biotra nsformation of thebaine by Mucor piriformis. Minor metabolites identified a re isomeric thebaine N-oxides. Among isomeric thebaine N-oxides, the one wi th the equatorial oxygen attached to the nitrogen is relatively unstable. R esting cells, grown in the presence of thebaine for 24 hr, efficiently conv erted thebaine into northebaine (similar to 77% conversion). Similar experi ments carried out with northebaine and isomeric thebaine N-oxides as substr ates, revealed that while northebaine and the stable thebaine N-oxide are p roved to be resistant to further transformation, the unstable thebaine N-ox ide nonenzymatically rearranges to 6, 7, 8, 9, 10, 14-hexadehydro-4, 5-epox y-3, 6-dimethoxy-17-methylthebinan and 6, 7, 8, 9, 10, 14-hexadehydro-3, 6- dimethoxythebinan-4-ol. These studies support the idea that N-demethylation of thebaine is not proceeding via the N-oxide intermediate.