One-Pot Synthesis of Glutathione Trisulfide from Oxidized Glutathione

The excellent medicinal efficacy of glutathione trisulfide, an endogenous compound consisting of sulfane sulfur and two molecules of reduced glutathione, has been reported in recent years. However, no efficient procedure for the synthesis of trisulfide is yet available. Herein, we investigated the optimal conditions for the oxidation reaction of oxidized glutathione to thiosulfinate and its subsequent trisulfidation reaction using commercially available materials. The optimized one-pot reactions enabled the isolation of glutathione trisulfide dihydrate by crystallization on a 20 g scale in high yield (up to 74% for the two steps, >95% purity). Liquid chromatography-mass spectrometry/MS (LC-MS/MS) measurements using Na