CHEMICAL-PROPERTIES OF THE ULTIMATE METABOLITES OF 2-AMINO-5-PHENYLPYRIDINE (PHE-P-1) AND ITS ORTHO-METHYL DERIVATIVE

The reactivity of the N-acetoxy metabolite of 2-amino-5-phenylpyridine (Phe-P-l), a pyrolysis product of phenylalanine, towards 2'-deoxyguan osine (dG), 2'-deoxyguanosine-3'-monophosphate (dGMP) and DNA was stud ied and compared with that of the ortho-methyl derivative. Reaction of 2-acetoxyamino-5-phenylpyridine (N-OAc-APP) with dG resulted in subst itution at the 8-position of this nucleoside by the ortho carbon of th e amine. The major reaction, however, was acetylation of dG. Iii contr ast, 2-acetoxyamino-3-methyl-5-phenylpyridine (N-OAc-MeAPP) mainly att acked the 8-position of dG by the exocyclic nitrogen and hardly any ac etylation of the nucleoside occurred. The adducts were chromatographic ally isolated and characterized by their mass and NMR spectra. Upon re action of N-acetoxy compounds with DNA and dGMP, formation of the same adducts was observed, besides the formation of minor amounts of unide ntified compounds, as was established by P-32-postlabeIIing analysis. The amount of DNA-bound amine, formed by the interaction of N-OAc-APP with DNA, was similar to 15 times smaller than that observed after the reaction with the corresponding ortho-methyl derivative under the sam e conditions.