title: gem-Difluorocarbadisaccharides: restoring the exo-anomeric effect.
abstract: Molecular mimicry is an essential part of the development of drugs and molecular probes. In the chemical glycobiology field, although many glycomimetics have been developed in the past years, it has been considered that many failures in their use are related to the lack of the anomeric effects in these analogues. Additionally, the origin of the anomeric effects is still the subject of virulent scientific debates. Herein, by combining chemical synthesis, NMR methods, and theoretical calculations, we show that it is possible to restore the anomeric effect for an acetal when replacing one of the oxygen atoms by a CF2 group. This result provides key findings in chemical sciences. On the one hand, it strongly suggests the key relevance of the stereoelectronic component of the anomeric effect. On the other hand, the CF2 analogue adopts the natural glycoside conformation, which might provide new avenues for sugar-based drug design.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Institut Universitaire de France, UMR CNRS 8232, IPCM, 4, place Jussieu, 75005 Paris (France).
authors.forename: Bixue
authors.initials: B
authors.lastname: Xu
authors.forename: Luca
authors.initials: L
authors.lastname: Unione
authors.forename: Joao
authors.initials: J
authors.lastname: Sardinha
authors.forename: Shaoping
authors.initials: S
authors.lastname: Wu
authors.forename: Mélanie
authors.initials: M
authors.lastname: Ethève-Quelquejeu
authors.forename: Amelia
authors.initials: A
authors.lastname: Pilar Rauter
authors.forename: Yves
authors.initials: Y
authors.lastname: Blériot
authors.forename: Yongmin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Sonsoles
authors.initials: S
authors.lastname: Martín-Santamaría
authors.forename: Dolores
authors.initials: D
authors.lastname: Díaz
authors.forename: Jesus
authors.initials: J
authors.lastname: Jiménez-Barbero
authors.forename: Matthieu
authors.initials: M
authors.lastname: Sollogoub
mesh_terms: D000080:Acetals / Q000737:chemistry; D002236:Carbohydrate Conformation; D004187:Disaccharides / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D018716:Molecular Mimicry; D010100:Oxygen / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000080:Acetals; D004187:Disaccharides; D010100:Oxygen
keywords: NMR spectroscopy; anomeric effect; conformation analysis; fluorine; glycosides