Preparation of halonitroarenes via diazotization of nitroaromatic amines. Starting materials for the synthesis of aminoarylcysteine derivatives

Abstract

S-(2-aminoaryl)cysteines are a presumed cysteine adducts formed from mutagenic and carcinogenic arylamines and nitroarenes. Both arylamines and nitroarenes are metabolically activated to corresponding arylnitrenium ions which can bind to the nucleophilic sites in biomolecules such as proteins and nucleic acids. When reaction with cysteine SH groups in proteins such as globin and albumin, arylnitrenium ions form adducts (Scheme 1). Hydrolytic cleavage of such protein adducts can release S(aminoaryl)cysteines, which are potentially useful biomarkers of cumulative exposure to mutagenic and carcinogenic aromatic amines. Such adduct has been recently identified in globin and plasma proteins of rats dosed with strongly mutagenic 3- nitrobenzanthrone (Linhart et al., 2017). The aim of this project is to prepare several fluoro- and bromonitroarenes, which will be further used as starting materials for the synthesis of aminoarylcysteines. Authentic samples of aminoarylcysteines are needed for toxicological studies on the formation and elimination of globin adducts formed in vivo in the course of metabolism of mutagenic and carcinogenic arylamines and nitroarenes.