Preparation of N-tBOC L-glutathione dimethyl and di-tert-butyl esters:: Versatile synthetic building blocks

The title L-glutathione derivatives, containing acid- and base-labile esters, respectively, were obtained in good overall yields. N-(BOC)-B-t L-glutathione dimethyl ester was prepared via Fischer esterification of L-glutathione disulfide (GSSG) using HCl in dry methanol, protection of the amine with (t)Boc(2)O, and tributylphosphine cleavage of the disulfide in wet isopropanol. Alternatively, Fischer esterification and (t)Boc-protection of L-glutathione (GSH) also furnished N-(t)Boc glutathione dimethyl ester accompanied by a small amount of S-(t)Boc that was removed chromatographically. The di-tert-butyl ester was obtained by S-palmitoylation of GSH in TFA as solvent, N-(t)Boc-protection, esterification using (BuOH)-Bu-t mediated by diisopropylcarbodiimide/copper(I) chloride, and saponification of the thioester. These L-glutathione derivatives are versatile synthetic building blocks for the preparation of S-glutathione adducts. (c) 2006 Elsevier Ltd. All rights reserved.