ISSN:
0009-2940
Keywords:
O-α-aminoacylation, activation of aromatic amines by
;
Bionucleophiles, model reactions with
;
N-[(Deoxy)guanosine-8-yl]arylamine adducts of monocyclic aromatic amines
;
8-(4-Methylanilino)-5′-guanosinemonophosphate, in-vitro-formation of
;
Phenacetin, analog of the ultimate carcinogen
;
Chemistry
;
Inorganic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
N-Aryl-O-(α-aminoacyl)hydroxylamine: Model Reactions with Deoxyguanosine, Guanosine and 5′-Guanosinemonophosphate for the Activation of Monocyclic Aromatic Amines (e.g. Phenacetin) into Ultimate CarcinogensIn in vitro model reactions of the activation of monocyclic aromatic amines by α-amino acids it is shown that α-amino-hydroxamic acids 8 and 9 rearrange base-catalyzed to N-(α-aminoacyloxy)arylamines 10 and 11 which react with bionucleophiles such as deoxyguanosine (dG) (12), guanosine (G) (13) and 5′-guanosinemonophosphate (5′-GMP) (14) to form adducts. We describe the regioselective formation of the C-8 adducts of 4-chloroaniline (15), aniline (16), 4-methylaniline (17), and 4-methoxyaniline (18), respectively, [“N-(deoxyguanosine-8-yl)anilines”], and also of N-(guanosine-8-yl)-4-methylaniline (21) and 8-(4-methylanilino)-5′-guanosinemonophosphate (22). Similar reactions of the N-(acetoxy)arylamines 20, which are very likely to be “ultimate” carcinogens of aromatic amines, lead to the same C-8 adducts 15-18, 21, and 22 in comparable yields. These in vitro reactions thus show that the N-(α-aminoacyloxy)arylamines 10 and 11 react like the N-(acetoxy)anilines 20 as “ultimate” carcinogens. Therefore, the activation of aromatic hydroxylamines by O-α-aminoacylation is of similar quality as by O-acetylation.
Additional Material:
3 Tab.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/cber.19901230820
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