gem-Difluorocarbadisaccharides: Restoring the exo-Anomeric Effect

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 th...

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Published in:Angewandte Chemie International Edition 2014-09, Vol.53 (36), p.9597-9602
Main Authors: Xu, Bixue, Unione, Luca, Sardinha, Joao, Wu, Shaoping, Ethève-Quelquejeu, Mélanie, Pilar Rauter, Amelia, Blériot, Yves, Zhang, Yongmin, Martín-Santamaría, Sonsoles, Díaz, Dolores, Jiménez-Barbero, Jesus, Sollogoub, Matthieu
Format: Article
Language:English
Subjects:
Acetals - chemistry
anomeric effect
Carbohydrate Conformation
Catalysis
Chemical Sciences
conformation analysis
Disaccharides - chemical synthesis
Drugs
fluorine
Glycosides
Magnetic Resonance Spectroscopy
Mathematical analysis
Models, Molecular
Molecular Mimicry
NMR spectroscopy
Nuclear magnetic resonance
Organic chemistry
Origins
Other
Oxygen - chemistry
Oxygen atoms
Renovating
Restoration
Stereoisomerism
Synthesis
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Summary: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. Taking effect: The combination of chemical synthesis, NMR methods, and calculations 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 as it strongly suggests the importance of the stereoelectronic component for the anomeric effect, and may open new avenues for sugar‐based drug design.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201405008