A new synthesis of glutathione via the thiazoline peptide.

A convenient synthesis of glutathione (GSH) by the use of minimal protecting groups was investigated. N-Formyl-L-2-amino-4-cyanobutyric acid ethyl ester was condensed with ethyl L-cysteinylglycinate to give (4R)-2-[(3S)-3-ethoxycarbonyl-3-(formylamino)propyl]-4-(ethoxycarbonylmethylcarbamoyl)-2-thiazoline. This compound was saponified in aqueous acetone at −15–−20 °C and subsequently treated with dilute H2SO4 (pH 4) to yield formylglutathione, whose formyl group was then hydrolyzed with 0.5 M (1 M=1 mol dm−3) H2SO4 to give free GSH. For purification, this was changed to a copper thiolate, which was then decomposed with H2S to afford pure GSH.