Microbial models of mammalian metabolism: biotransformations of phenacetin and its O-alkyl homologues with Cunninghamella species

Abstract

1. The analgesic compound phenacetin and its O-alkyl homologues were metabolized by Cunninghamella elegans to yield the O-dealkylation product paracetamol (acetaminophen), and metabolites resulting from Ω-1 hydroxylation and further oxidations.

2. Structural identification was based upon physical, spectral and chromatographic comparisons of isolated metabolites with synthetic standards generated by alkylation of paracetamol with the appropriate alkyl halide, epoxide, or α,β-unsaturated ketone.

3. The rank order of O-dealkylation within the homologous series based upon either substrate disappearance or phenol formation was found to be ethylisopropyl n-propyl > n-butyl > methyl.