4-Hydroxybenzyl-substituted glutathione derivatives from Gastrodia elata

Abstract

Seven new 4-hydroxybenzyl-substituted glutathione derivatives (2–8), together with a known analogue (1), were isolated from the aqueous extract of Gastrodia elata Blume rhizomes. Their structures were determined by using spectroscopic and chemical methods. The absolute configurations of 1–8 were assigned by using Marfey's method, combined with comparing the NMR and CD spectroscopic data of sulfoxide moieties in 3–6 with those of S-(4-hydroxybenzyl)cysteine sulfoxide stereoisomers (9–12) synthesized as authentic samples. The configurations of 9–12 were confirmed by electronic CD calculations based on the quantum-mechanical time-dependent density functional theory. Furthermore, the structures of 1, 3, 5, 7, and 8 were verified by synthesis. Compound 3 was active against serum deprivation-induced PC12 cell damage and synthetic 9–14 exhibited activity against Fe2+-cysteine induced rat liver microsomal lipid peroxidation.