Use of superacid conditions to highlight unprecedented transient intermediates in glycochemistry – OXYCARB

What makes identifying glycosyl cations so tricky is their very short duration (estimated half-life of one picosecond in an organic environment). To overcome this obstacle, researchers used «super-acidic” conditions to generate, stabilise and study the reaction of glycosylation and its intermediates via low-temperature nuclear magnetic resonance (NMR). The use of super-acidic environments stronger than concentrated sulfuric acid has enabled researchers to create chemical reactions with no equivalents in traditional organic environments.

This approach has made it possible for the first time ever to identify and characterise some of the cationic intermediates involved in glycosylation reactions. This results should have a significant technological impact as glycosylation is a major reaction in biomass conversion. Several international research groups contacted us to establish scientific collaborations.

This approach has made it possible for the first time ever to identify and characterise some of the cationic intermediates involved in glycosylation reactions. This results should have a significant technological impact as glycosylation is a major reaction in biomass conversion. Several international research groups contacted us to establish scientific collaborations.

Two papers are currently in preparation:

Research carried out by Oxycarb was even cited by an article in the respected chemical sciences journal Nature Chemistry (2016, 8, 186-191). This article has been the focus of a News & Views in the same Nature Chemistry issue (2016, 8, 99-100). It is mentioned in the titles of the journal cover. (Carbohydrate chemistry : cations caught in the act). Our results have been highlighted by CNRS (http://www.cnrs.fr/inc/communication/direct_labos/bleriot.htm) and ANR (http://www.agence-nationale-recherche.fr/informations/actualites/detail/chimie-les-partenaires-du-projet-oxycarb-mettent-en-evidence-une-espece-chimique-jusquici-jamais-observee/). Finally, a one day symposium on this discovery has been organized in Poitiers on the 14th of December 2015 (http://ic2mp.labo.univ-poitiers.fr/noticias/glycosyl-cation-day-3/).

The central reaction in glycochemistry is that of glycosidic bond formation, or glycosylation, but surprisingly the details of this critical reaction remain relatively poorly understood. For example, the glycosyl oxocarbenium ion is considered by most to play a key role in glycosylation but is still a hypothetical species. Neighboring group participation is also a widespread reaction in glycochemistry. The mechanism of neighboring group participation-directed glycosylation by vicinal esters proceeds through the intermediacy of cyclic dioxalenium ions. Despite many excellent contributions in the field of glycochemistry, both glycosyl oxocarbenium and dioxalenium ions have yet to be observed experimentally. One might consider, therefore, that the ?eld remains at the level at which carbenium ion chemistry in general found itself in the 1950s. Consequently, their actual observation by spectroscopic means would be a welcome advance in the ?eld. By combining carbohydrate and superacid chemistries with powerful NMR and molecular modelling methodology, we expect to visualise such transient species for many important monosaccharides and analyze their conformation for the first time. If successful, this approach should allow to decipher the conformational itinerary of glycosyl donors by taking snapshots along the glycosylation pathway. Furthermore this data could be used to rationalize the stereochemical outcome of glycosylation reactions and quenching of such species with various nucleophiles would be interesting in the field of glycosylation.