Access to deuterated glycosides for biological applications via Hydrogen Isotope Exchange – Glyco-CD

Deuterated carbohydrates and glycoconjugates are essential tools in numerous fields such as drug development, diagnostics, elucidation of biomacromolecules, analyses of biological samples by mass spectrometry or the study of biomolecular dynamics. However, despite their high added-value, access to deuterated glycosides is currently challenging and expensive. This problem is largely due to the lack of universal methods for the labelling of a large variety of glycosides with the desired regio- and enantio-selectivities. Glyco-CD aims at developing innovative approaches for the hydrogen/deuterium exchange of carbohydrates. Methods using metallic catalysts will be developed to incorporate deuterium atoms regioselectively without requiring the synthesis of labelled precursors. Surface engineering of catalysts will be carried out to gain access to useful and diversely labelled carbohydrates: regioselectively mono- and multi-labelled up to per-deuterated ones. Protecting group strategies using directing groups able to chelate the metallic catalytic species and transient protecting groups targeting diol systems, will also be investigated to allow for chemo- and hence regio-selective hydrogen isotope exchanges (HIE). The implementation of flow chemistry will also permit a rapid and low-cost gram-scale production to reach market and commercialization in fine.
One major application of the deuterated carbohydrates will be the investigation of metabolic processes using in cellulo and in vivo deuterium metabolic imaging (DMI), an innovative imaging approach with a large potential for biomedical research. Novel DMI probes will be developed such as deuterated Kdo for in cellulo detection of pathogenic bacteria and deuterated fructose, an original deuterated probe for the study of metabolic disorders linked to fatty liver disease.
Glyco-CD will allow a straightforward and cost efficient access to a large panel of valuable deuterated carbohydrates. Glyco-CD will:
(1) Develop new catalytic systems for the mono-, multi- and per-deuteration of carbohydrates with a total regio- and stereocontrol
(2) Study the influence of deuterated carbohydrates on metabolic processes
(3) Develop new probes for in cellulo and in vivo deuterium metabolic imaging