New Precursors to 3-Sulfanylhexan-1-ol? Investigating the Keto–Enol Tautomerism of 3-S-Glutathionylhexanal

Abstract

The volatile thiol compound 3-sulfanylhexan-1-ol (3SH) is a key impact odorant of white wines such as Sauvignon Blanc. 3SH is produced during fermentation by metabolism of non-volatile precursors such as 3-S-gluthathionylhexanal (glut-3SH-al). The biogenesis of 3SH is not fully understood, and the role of glut-3SH-al in this pathway is yet to be elucidated. The aldehyde functional group of glut-3SH-al is known to make this compound more reactive than other precursors to 3SH, and we are reporting for the first time that glut-3SH-al can exist in both keto and enol forms in aqueous solutions. At wine typical pH (~3.5), glut-3SH-al exists predominantly as the enol form. The dominance of the enol form over the keto form has implications in terms of potential consumption/conversion of glut-3SH-al by previously unidentified pathways. Therefore, this work will aid in the further elucidation of the role of glut-3SH-al towards 3SH formation in wine, with significant implications for the study and analysis of analogous compounds.

Exploring the Equilibrium between Glut3SHal and Glut3SH–SO3: A Method for the Quantification of These Compounds in Wine

“…5,6,17 However, keto−enol tautomerization in the deuterated NMR solvent, D 2 O, leads to the incorporation of deuterium atoms at C2 over time, which renders interpretation of the complex spectrum even more challenging. 5 In an effort to mitigate the impact of isotopologue formation, the bisulfite addition reaction was studied over short periods of time. The spectrum of a sample of glut3SHal in D 2 O was analyzed by qNMR, with KHP as the internal standard, recording the peak areas of H-1 and H-1* (see Figure 1).…”

“…3 Throughout the early literature, the absence of a precursor to glutathionylated 3SH (glut3SH) was conspicuous, because the chemical addition of glutathione can happen only to the α,β-unsaturated aldehyde and not the unsaturated alcohol. 3 Glut3SHal was first identified after introduction of a deuterium-labeled analogue of E-2-hexenal, d 8 - (3,4,4,5,5,6,6,6)-E-2-hexenal, to grape must while demonstrating that most glut3SH is produced after the harvest of the grape berry. 4 The aldehyde functional group retained in glut3SHal results in a molecule with distinct and enhanced reactivity compared to other thiol precursors, such as glut3SH and cysteinylated 3SH (cys3SH).…”

“…With recent work reporting the synthesis of a stable isotope labeled analogue of glut3SHal, d 8 - (3,4,4,5,5,6,6,6)-3S-glutathionylhexanal, and glut3SH−SO 3 by association, quantitative analytical methods are now within reach of the scientific community. 17 As such, this work set out to explore the equilibrium between glut3SHal and glut3SH−SO 3 via a range of spectroscopic methods.…”

“…The aldehyde functional group retained in glut3SHal results in a molecule with distinct and enhanced reactivity compared to other thiol precursors, such as glut3SH and cysteinylated 3SH (cys3SH). , Indeed, attempts to synthesize thiol precursors by the addition of cysteine to E -2-hexenal, analogous to early syntheses of glut3SH, primarily lead to the formation of the diadduct and cyclized forms (see Scheme ), − emphasizing the retention of the reactivity of the aldehyde moiety.…”

Unraveling the Mystery of 3-Sulfanylhexan-1-ol: The Evolution of Methodology for the Analysis of Precursors to 3-Sulfanylhexan-1-ol in Wine

“…The synthesis of an isotopically labeled IS, G3Shal-d 8 , has been reported [58], but the quantification of G3Shal in real samples still poses a challenge. G3Shal has also been shown to undergo tautomerism in wine-like solutions, which could give rise to additional precursors, but this requires further study [86].…”