Primaquine: metabolism by microorganisms and 13C nuclear magnetic resonance assignments

Primaquine (I), a 6-methoxy-8-aminoquinoline derivatives used for the treatment of malaria, has been subjected to metabolic studies using microorganisms. A total of 77 microorganisms (fungi and Streptomyces spp.) were evaluated for their ability to metabolize primaquine. Of these, 23 were found to convert primaquine to one or more metabolites (thin-layer chromatography analysis). Preparative scale fermentation of primaquine with four different microorganisms resulted in the isolation of two metabolites, identified as 8-(4-acetamido-1-methylbutylamino)-6-methoxyquinoline (II) and 8-(3-carboxyl-1-methylpropylamino)-6-methoxyquinoline (III). The structures of the metabolites were proposed based primarily on a comparison of the 13C nuclear magnetic resonance spectra of II and the methyl ester of III (IV) with that of primaquine. The structures of both metabolites II and III were confirmed by direct comparison with authentic samples.