When organic chemistry contributes to the understanding of metabolism mechanisms

Abstract

Many compounds of interest in wine are difficult to analyze since they are present in very small quantities or they are unstable. The need for reliable data led scientists to develop complex method in order to overcome the analytical difficulties and provide accurate quantitative data for grape or wine characterization.

For 10 years, we developed several chemical strategies to obtain analytical standards either as labelled analogues or as diastereomers to develop SIDA and DIDA analytical methods, respectively. These quantification methods afforded accurate and reliable results by suppressing analytical bias due to sample preparation. Several examples will be presented from deuterated analogues: varietal thiols [1], thiol precursors [2], Ochratoxin A [3], and diastereoisomers: Ochratoxin A [4] and hydroxycinnamic acids [5].

Another interesting application based on synthetic compounds lies in their possible exploitation as tracers. Indeed, the scale-up and optimization of chemical syntheses from μg to mg levels provided us with substantial amounts of molecules that could be used in metabolism studies. For example, we recently used labelled thiol precursors as tracers in Sauvignon Blanc musts for metabolism studies. Degradation of such tracers was monitored to highlight several key interconversion mechanisms and bring new elements in varietal thiol biogenesis knowledge [6]. In these applications, the choice of the labelling position (for Ochratoxin A for instance) or multilabelling possibilies (for thiol precursors) offer future opportunity to investigate detoxification process or to obtain insight in the metabolism of aroma precursors, respectively.

References

1. a) A. Roland, R. Schneider, A. Razungles and F. Cavelier, Varietal thiols in wine: Discovery, Synthesis and Applications, Chem. Rev. 2011, 111, 7355. b) R. Schneider, Y. Kotseridis, J.-L. Ray, C. Augier and R.Baumes, Quantitative determination of sulfur-containing wine odorants at sub parts per billion levels.
2. Development and application of a stable isotope dilution assay, J. Agri. Food Chem., 2003, 51, 3243. 2. H.Bonnaffoux, A.Roland, E.Rémond, S.Delpech, R.Schneider, F.Cavelier, First identification and quantification of S-3- (hexan-1-ol)-γ-glutamyl-cysteine in grape must as a potential thiol precursor, using UPLC-MS/MS analysis and stable iso-tope dilution assay, Food Chem., 2017, 237, 877.
3. A.Bouisseau, A.Roland, R.Schneider and F.Cavelier, First Synthesis of a Stable Isotope of Ochratoxin A Metabolite for a Reliable Detoxification Monitoring, Org. Lett., 2013, 15, 3888.
4. A.Roland, P.Bros, A.Bouisseau, F.Cavelier and R.Schneider, Analysis of Ochratoxin A in musts and wines by LCMS/MS: Comparison of Stable Isotope Dilution Assay and Diastereomeric Dilution Assay Methods, Anal. Chim. Acta, 2014, 818, 39.
5. F. Cavelier, A. Roland, A. Bouisseau, J. Martinez, R. Schneider. Method for the esterification of polar molecules, WO 2015 011230
6. H. Bonnaffoux, S. Delpech, E. Rémond, R. Schneider, A. Roland, F. Cavelier, Revisiting the evaluation strategy of varietal thiol biogenesis, Food Chem., 2018, 268, 126.