Synthesis of α-Deuterium-Labelled Cyclohexylamine and Its Deamination by Rabbit Liver Microsomes

Abstract

In order to investigate the isotope effect on the microsomal oxidative deamination of cyclohexylamine, α-deuterium(D)-labelled cyclohexylamine was synthesized. The deuterium labelling was found exclusively at the α-position with a purity of greater than 99 atom percent. Metabolic studies in vitro indicate that a significant deuterium isotope effect operates in the oxidative deamination of α-D-labelled cyclohexylamine. On incubation with rabbit liver microsomes in the presence of reduced nicotinamide adenine dinucleotide phosphate (NADPH) and oxygen, the ratio of apparent deamination rate constants (k_H/k_D) was 2.0±0.2 (mean±S.D.).