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-(t)Boc 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 (t)BuOH 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.
Falck
J R
JR
Departments of Biochemistry and Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9038, USA. j.falck@UTSouthwestern.edu
Sangras
Bhavani
B
Capdevila
Jorge H
JH
D002855:Chromatography, Thin Layer; D004952:Esters / Q000138:chemical synthesis; D005978:Glutathione / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D019308:Palmitic Acid / Q000737:chemistry; D012997:Solvents
D004952:Esters; D007202:Indicators and Reagents; C517841:N-tBoc L-glutathione di-tert-butyl ester; C517840:N-tBoc L-glutathione dimethyl ester; D012997:Solvents; D019308:Palmitic Acid; D005978:Glutathione