An Improved Process for Preparation of S-Acetyl-l-glutathione

Abstract

An efficient one-step synthesis of S-acetyl-L-glutathione has been developed in a DMF−TFA mixed solvent with CoCl 2 as catalyst. This process not only has the advantages of selective acylation of the glutathione thiol group without involving the free amino but also highlights recycling of the relatively costly solvent TFA, which improves the yield to 91% and quality to 99.7%. The reaction is cost-effective, efficient, and easy to scale-up.

Practical and Selective Syntheses of S‐Acyl and N‐Acyl Glutathiones with N‐Acyl Imidazoles in Water

“…Because of the high solubility of GSH and N ‐acyl imidazole in water, we decided to initially treat GSH with readily available N ‐acetyl imidazole to selectively synthesize the industrially important bioactive compound S ‐acetyl‐L‐glutathione [9] in weakly basic aqueous solution at room temperature. Multiple experiments were performed to screen for an effective base and the proper molar equivalents; the results are presented in Table 1.…”

Large-Scale Preparation of N-Butanoyl-l-glutathione (C4-GSH)

“…However, a protection/deprotection event introduces at least two steps into a sequence, incurring costs from additional reagents and waste disposal, and generally leads to a reduced overall yield. The chemoselective functionalization of the highly reactive cysteine residue and the (one or both) terminal carboxyl group has been particularly successful, whereas the more challenging modification on the α-amino group of the glutamic acid residue has only become a research focus recently (Figure ). Published methods to synthesize nonamphoteric derivatives of N -acyl glutathiones have utilized the following approaches: (a) N -acylation of GSSG with an activated ester, followed by reduction; (b) use of a trityl group to protect the thiol group of GSH, then N -acylation followed by trityl group deprotection; (c) use of 4-nitrobenzoyl to protect the thiol group of GSH, then N -acylation with 1-acyl-1 H -benzotriazole followed by deprotection using pyrrolidine in dry tetrahydrofuran (THF)–methanol for 4 h; or (d) solid-phase peptide synthesis using the appropriate fluorenylmethyloxycarbonyl amino acid and carboxylic acid under basic conditions with hydroxybenzotriazole/ N , N -diisopropylethylamine activation in anhydrous N -methylpyrrolidone .…”

Highly selective acylation of polyamines and aminoglycosides by 5-acyl-5-phenyl-1,5-dihydro-4H-pyrazol-4-ones

“…The linkage to the acyl group has included N -imidazolyl 4a – g and N -benzotriazolyl, 4h – m succinimidyloxy, 5 cyanide, 6 sulfonamide, 7 trichloromethyl, 8 enolates, 9 and, most recently, boron trifluoride. 10 Selectivity in acyl transfer has become an important goal with achievements evolving beyond chemoselection (OH vs. SH vs. NH acylation) 11 to selective acylation of primary amines over secondary amines. 10 , 11 Although the use of enzymes 12 or RNA-based aptameric protective groups 13 for highly regio- and site-selective acylation of di- and polyamines has been reported, small molecule acyl transfer reagents that provide high to exclusive regiocontrol remain under-investigated.…”