Biological Chemistry
Team members
Research Topics
Since its creation in September 2002, our team has focused on developing stereoselective methods for accessing chiral fluorinated compounds. The introduction of a fluorinated group within a molecule makes it possible to significantly modify its stereoelectronic properties, which has the effect of modifying its physical and biological properties. Thus the demand for fluorinated synthons is growing, both in the field of pharmaceutical chemistry and that of materials. In this context, we have developed rapid and stereoselective pathways to various fluorinated compounds.
Fluorinated chiral compounds
Since its creation in September 2002, our team has focused on developing stereoselective methods for accessing chiral fluorinated compounds. The introduction of a fluorinated group within a molecule makes it possible to significantly modify its stereoelectronic properties, which has the effect of modifying its physical and biological properties. Thus the demand for fluorinated synthons is growing, both in the field of pharmaceutical chemistry and that of materials. In this context, we have developed rapid and stereoselective pathways to various fluorinated compounds.
Metal-catalyzed functionalisation
Access to unnatural glycosides by metal-catalyzed functionalisation of glycal substrates
Development of new access to glycoconjugates has become of great interest in synthetic chemistry. In particular, glycoconjugates possessing an unnatural bond are largely studied due to their enzymatic and chemical stabilities towards C-O and C-N natural links.
Our expertise deals with the metal-catalyzed functionalisation of glycal substrates using two different reactivities:
– Cross-coupling reactions on 2-iodoglycal starting compounds for the formation of C-C, C-N or C-P bonds : palladium-catalyzed aminocarbonylation (A), carbonylative Suzuki-Miyaura reaction (C), cyanation in aqueous media (D) dual nickel/copper-catalyzed amidation (E) and palladium-catalyzed phosphonylation (F).
– Directed C-H functionalisation reactions of the pseudo-anomeric position of C2-amidoglycals: palladium-catalyzed C-H arylation and nickel-catalyzed C-H alkenylation (B).
One of the limitations to the use of peptides as therapeutic agents is their rapid degradation by peptidases as well as their low lipophilicity. Our laboratory is interested in the development of efficient peptide coupling reactions that allow the incorporation of enantiopure α-trifluoromethylated amino acids into peptide chains. Their use is of great interest due to the unique properties of the fluorine atom. Their incorporation into peptide chains is promising due to conformational constraints, electronic effects and increased hydrophobicity induced by fluorinated groups. Thus an increased metabolic stability with respect to proteases and original three-dimensional structures are expected. The local increase in the hydrophobic character can make it possible to facilitate the passage of the blood-brain barrier. Moreover, these fluorinated peptides have a strong analytical potential as an NMR probe (19F) for the elucidation of structures, the understanding of biological mechanisms and the pharmacokinetic studies of these non-proteogenic peptides.
Fluorinated Organocatalysts
Bifunctional iminophosphorane/(thio)urea catalysts
Recently, bifunctional organocatalysts have enabled the development of highly stereoselective transformations due to their ability to simultaneously organize and activate electrophilic substrates through hydrogen bonding and pro-nucleophilic reagents through deprotonation. However, slow reaction rates and high catalyst loadings remain major limitations in this field. Additionally, some limitations persist regarding the compatible reaction partners with these catalysts.
In our laboratory, we are investigating the design and synthesis of new bifunctional iminophosphorane/(thio)urea catalysts containing a chiral trifluoromethyl group (F-BIMP), offering improved reactivity while maintaining high levels of enantiomeric control.
