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

Bioorg Med Chem. 2007 Jan 15;15(2):1062-6. doi: 10.1016/j.bmc.2006.10.022. Epub 2006 Oct 25.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Chromatography, Thin Layer
  • Esters / chemical synthesis
  • Glutathione / analogs & derivatives*
  • Glutathione / chemical synthesis*
  • Indicators and Reagents
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Palmitic Acid / chemistry
  • Solvents

Substances

  • Esters
  • Indicators and Reagents
  • N-tBoc L-glutathione di-tert-butyl ester
  • N-tBoc L-glutathione dimethyl ester
  • Solvents
  • Palmitic Acid
  • Glutathione