THE FORMATION AND METABOLISM OF N-HYDROXYMETHYL COMPOUNDS .6. THE SYNTHESIS OF S-AMIDOMETHYL, S-UREIDOMETHYL, AND S-(1,3,5-TRIAZIN-2-YLAMINOMETHYL)-GLUTATHIONE DERIVATIVES

Treatment of N-hydroxymethyl and N-alkoxymethyl compounds with glutathione or N-acetylcysteine in trifluoroacetic acid affords the corresponding glutathione of N-acetylcysteine derivatives [N-acetyl-S-(4-tert-butylbenzamidomethyl)cysteine, N-acetyl-S-(N''-phenylureidomethyl)cysteine, N-acetyl-S-[N-[4,6,-bis(dimethylamino)-1,3,5-triazin-2-yl]-N-methylaminomethyl]cysteine, S-[N''-(4-chlorophenyl)ureidomethyl]glutathione trifluoroacetate salt hydrate, S-formamidomethylglutathione trifluoroacetate salt dihydrate, S-(4-tert-butylbenzamidomethyl)glutathione picrate, S-benzamidomethylglutathione trifluoroacetate salt hydrate and S-(N-phenylureidomethyl)glutathione trifluoroacetate salt hydrate] in high yield. Alkoxymethylureas [N-(4-nitrophenyl)-N''-methoxymethylurea, N-(4-chlorophenyl)-N''-methoxymethylurea and N''-ethoxymethyl-N-phenylurea] are formed by the condensation of ureas with formaldehyde and alcohols under basic conditions; the implications of this observation are discussed with reference to possible biochemical mechanisms. [N-Hydroxymethyl compounds are produced by the metabolism of drugs and other materials containing N-methyl groups, by preparations of murine liver.].