Glycosides of N-hydroxy-N-arylamine derivatives. Part 1. Synthesis and mutagenicity of O-glucosides of N-Hydroxy-N-arylamines and their acetohydroxamic acids

Abstract

N-Acetyl-N-arylamino β-D-glucopyranosides (7a–d) were synthesized by the orthoester glycosylation method via N-arylamino β-D-glucopyranosides (6a–d), and the N-acetyl amides, having an N–O–C-1 linkage in their molecules, were characterized by chemical, enzymatic, and spectral analyses. In the mutation assay using Salmonella typhimurium TA100 strain with or without various intracellular fractions of guinea pig liver, these glucosides (7a–d) were non-mutagenic per se, but showed mutagenic activity in the presence of the post-mitochondrial supernatant (S9) or the microsomal fraction (Ms), except for the glucoside (7a). Of the glucosides (7b–d), the compounds having fewer chlorine atoms were more effective in inducing mutations than were those having multiple chlorines. No mutagenic activity was observed in the presence of the soluble supernatant fraction (S10.5). The mutagenicity of the glucosides (7b–d) seemed to be due to the corresponding N-deacetylated compounds (6b–d) formed through hydrolysis by a microsomal deacetylase(s). The pathway of the metabolic activation of the glucosides (7b–d) is discussed.