Metabolic N-Hydroxylation of substituted acetophenone ixnines. I. Evidence for formation of isomeric oximes

Abstract

1. A series of chemically stable substituted acetophenone imines and their potential N-hydroxylated metabolites (i.e., oximes) have been synthesized and characterized by spectroscopic methods.

2. The enzymic N-hydroxylation of acetophenone imines in vitro has been demonstrated as a general metabolic pathway in several mammalian species including the guinea-pig.

3. The oxime metabolites were formed as mixtures of two geometric isomers, Z (syn-phenyl) and E(anti-phenyl), wherein the phenyl and hydroxyl group are cis and trans to each other respectively.

4. The E (anti-phenyl) isomer was the quantitatively predominant isomeric form metabolically produced by all species studied.

5. The relative proportions of the E and Z isomers in metabolic mixtures were found to be species dependent.