FURTHER INSIGHTS INTO THE OXIDATION CHEMISTRY OF NOREPINEPHRINE AND EPINEPHRINE IN THE PRESENCE OF CYSTEINE

Oxidations of dopamine (DA), norepinephrine (NE), and epinephrine (EPI ) at pH 7.4 in the presence of free L-cysteine (CySH) have been previo usly shown to generate a number of cysteinyl conjugates of these catec holaminergic neurotransmitters that serve as precursors of various dih ydrobenzothiazines (DHBTs). In this investigation it is demonstrated t hat oxidations of NE or EPI, but not DA, in the presence of free CySH also generate three previously unknown DHBTs: ihydro-5-hydroxy-2H-1,4- benzothiazine-3-carboxylic acid (A), ihydro-5-hydroxy-2H-1,4-benzothia zine-3-carboxylic acid (B), and -carboxy-3,6,7,8-tetrahydro-10-hydroxy benzo[1,2-b: 4,3-b']bis[1,4]thiazin-2-yl]-L-cystine (C). The beta-hydr oxy side chain residues of NE and EPI are required in order to form A- C, hence explaining the fact that these compounds are not formed upon oxidation of DA in the presence of CySH. A further new product unique to the oxidation of EPI in the presence of CySH at pH 7.4 is hylpyrrol o[2,3-h]-1,4-benzothiazin-3-yl]-L-cystine (D). Reactions pathways that account for formation of A-D are presented along with a discussion of their potential formation as aberrant metabolites in the brain in a n umber of neurodegenerative disorders. (C) 1997 Academic Press.