Synthesis of Peptides Containing S-(N-Alkylcarbamoyl)cysteine Residues, Metabolites of N-Alkylformamides in Rodents and in Humans

Article abstract of DOI:10.1021/jo00273a031

Hydrochloride salts of S-(N-methylcarbamoyl), S-(N-ethylcarbamoyl), and S-(N,N-dimethylcarbamoyl) derivatives of cysteine, N-acetylcysteine, and cysteinylglycine have been prepared.S-(N-Methylcarbamoyl)glutathione hydrochloride has also been synthesized.Protecting groups for amino and carboxylic acid functions were selected for their ability to solubilize the peptides in dichloromethane in which solvent the thiols were treated with alkyl isocyanates and with N,N-dimethylcarbamoyl chloride.Removal of S-(amidomethyl) protecting groups using mercury(II) acetate was found to cause some loss of N-(tert-butoxycarbonyl) groups.Elimination of disulfide was evident during coupling of disulfide derivatives of cysteine using mixed anhydride methods but not with a carbodiimide coupling agent.Mixed disulfide protections were reductively cleaved by propane-1,3-dithiol.Many of the deprotected S-carbamoyl amino acids and peptides are metabolites of the corresponding N-alkylformamides in rodents and in humans.