Thiomethylation and thiohydroxylation –a new pathway of metabolism of heterocyclic compounds

Abstract

1. G.l.c.-mass spectral analysis of t.l.c. fractions of urine samples of patients treated with 5-(2-chloroethyl)-4-methylthiazole (clomethiazole), has revealed two minor metabolites, each with two sulphur atoms.

2. Their structures were found to be 2-methylthio-clomethiazole and 5-acetyl-4-methyl-2-mercapto-thiazole, formed by thiomethylation and thiohydroxylation, respectively, of the original compound.

3. The structures of six other minor metabolites resulting from side-chain degradation have been elucidated.

4. The occurrence of metabolites with substituents at position 2 of the heterocyclic nucleus is assumed to be initiated by oxidative attack at the nitrogen, followed by nucleophilic substitution in position 2.