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N ‐Aryl‐ O ‐(α‐aminoacyl)hydroxylamine: Modellreaktionen mit Desoxyguanosin, Guanosin und 5′‐Guanosinmonophosphat zur Aktivierung monocyclischer aromatischer Amine (z. B. Phenacetin) zu ultimaten Carcinogenen
Author(s) -
Meier Chris,
Boche Gernot
Publication year - 1990
Publication title -
chemische berichte
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 0009-2940
DOI - 10.1002/cber.19901230820
Subject(s) - chemistry , deoxyguanosine , hydroxylamine , phenacetin , guanosine , aniline , aromatic amine , adduct , medicinal chemistry , amine gas treating , aryl , carcinogen , stereochemistry , organic chemistry , biochemistry , alkyl , chromatography
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 Carcinogens In 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 .