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

Northebaine was identified as the major metabolite formed during the biotransformation of thebaine by Mucor piriformis. Minor metabolites identified are isomeric thebaine N-oxides. Among isomeric thebaine Noxides, the one with the equatorial oxygen attached to the nitrogen is relatively unstable. Resting cells. grown in the presence of thebaine for 24 hr, efficiently converted thebaine into northebaine (-77% conversion). Similar experiments carried out with northebaine and isomeric thebaine N-oxides as substrates, revealed that while northebaine and the stable thebaine N-oxide are proved to be resistant to further transformation, the unstable thebaine N-oxide nonenzymatically rearranges to 6, 7, 8, 9, 10, 14-hexadehydro-4, 5-epoxy-3. 6-dimethoxy-17methylthebinan and 6, 7, 8,9, 10, l4-hexadehydro-3. 6-dimethoxythebinan-4-01. These studies support the idea that N-demethylation of thebaine is hot proceeding via the N-oxide intermediate.