Stereochemistry of the Metabolic Incorporation of Oxygen into (+)- and (-)-N-Benzylamphetamine

Abstract

1. Both (+)- and (-)-N-benzylamphetamine undergo α-carbon and N-oxidation to form N-dealkylated, deaminated and N-oxidized metabolites during incubation with fortified rabbit liver homogenates.

2. Quantitative determination of the metabolites based on specific g.l.c. procedures showed that all activities are localized in the microsomal fraction of rabbit liver.

3. N-Dealkylation, deamination and nitrone and secondary hydroxylamine formation are stereoselective.

4. The characteristics of the enzyme-substrate interactions for both isomers of N-benzylamphetamine indicate that at least two distinct enzyme systems are involved in the N-oxidation and α-carbon processes, or a single enzyme possessing an active site with differing conformational requirements for the two oxidative processes.