Unusual reactions of the model carcinogen N-acetoxy-N-acetyl-2-amino-alpha-carboline.
The aqueous solution reactions of the title compound, 1, were examined for comparison to those previously reported for another model carcinogen N-pivaloyloxy-2-amino-alpha-carboline, 2. Both of these are models for the ultimate carcinogenic metabolites of 2-amino-alpha-carboline (AalphaC), a food-derived heterocyclic amine mutagen and carcinogen. The present study was undertaken to determine the effect of the N-acetyl group on the chemistry of such compounds. The N-acetyl group slows down N-O bond cleavage by a factor of (5.5 x 10(3))-fold. This allows other reactions not observed in 2, or in other model carcinogens, to be observed. Among these are acyl-transfer reactions to the aqueous solvent, both uncatalyzed and catalyzed by N3-. In addition, the conjugate acid of 1, 1H+, is subject to a spontaneous decomposition not previously observed in other esters of heterocyclic hydroxylamines or hydroxamic acids. This reaction yields the hydroxylamine, 5, and does so without the intermediacy of the hydroxamic acid, 3, and with 18O exchange from the solvent into the hydroxylamine O. This unique reaction may be caused by an intramolecular proton donation by the pyridyl N-H to the amide carboxyl that catalyzes an intramolecular nucleophilic attack by the carboxyl O of 1H+. A nitrenium ion pathway can still be detected for 1, but, unlike 2 and related esters, this reaction is in competition with other processes throughout the pH range of the study.
Novak
Michael
M
Department of Chemistry and Biochemistry, Miami University, Oxford, Ohio 45056, USA. novakm@muohio.edu
Nguyen
Thach-Mien
TM
D000577:Amides / Q000032:analysis / Q000737:chemistry; D000588:Amines / Q000737:chemistry*; D001386:Azides / Q000032:analysis / Q000737:chemistry; D002243:Carbolines / Q000737:chemistry*; D002273:Carcinogens / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D006877:Hydroxamic Acids / Q000032:analysis / Q000737:chemistry; D019811:Hydroxylamine / Q000032:analysis / Q000737:chemistry; D007700:Kinetics; D010103:Oxygen Isotopes; D013816:Thermodynamics
D000577:Amides; D000588:Amines; D001386:Azides; D002243:Carbolines; D002273:Carcinogens; D006877:Hydroxamic Acids; D010103:Oxygen Isotopes; D019811:Hydroxylamine