Fluoro-C-glycosides and fluoro-carbasugars, hydrolytically stable and synthetically challenging glycomimetics

Leclerc, E.; Pannecoucke, Xavier; Ethève-Quelquejeu, Mélanie; Sollogoub, Matthieu

doi:10.1039/c2cs35403a

Cited by 97 publications

(61 citation statements)

References 50 publications

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“…[15] For all these reasons, fluorinated glycomimetics have received careful attention. [16] Dependingo nt he substituted position, the fluorine substituent can have ar emarkable effect upon the physical andc hemical properties of the molecule. It could inducei ncrease of lipophilicity,d ecreasei np K a values of certain groups by OH-F electrostatic interaction, modulate the hydrogen-bond acceptor/donator ability or foster the presence of ap articular ring conformation.…”

Section: Introductionmentioning

confidence: 99%

Conformational Plasticity in Glycomimetics: Fluorocarbamethyl‐L‐idopyranosides Mimic the Intrinsic Dynamic Behaviour of Natural Idose Rings

Unione

Díaz

et al. 2015

Chemistry A European J

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Sugar function, structure and dynamics are intricately correlated. Ring flexibility is intrinsically related to biological activity; actually plasticity in L-iduronic rings modulates their interactions with biological receptors. However, the access to the experimental values of the energy barriers and free-energy difference for conformer interconversion in water solution has been elusive. Here, a new generation of fluorine-containing glycomimetics is presented. We have applied a combination of organic synthesis, NMR spectroscopy and computational methods to investigate the conformational behaviour of idose- and glucose-like rings. We have used low-temperature NMR spectroscopic experiments to slow down the conformational exchange of the idose-like rings. Under these conditions, the exchange rate becomes slow in the (19) F NMR spectroscopic chemical shift timescale and allows shedding light on the thermodynamic and kinetic features of the equilibrium. Despite the minimal structural differences between these compounds, a remarkable difference in their dynamic behaviour indeed occurs. The importance of introducing fluorine atoms in these sugars mimics is also highlighted. Only the use of (19) F NMR spectroscopic experiments has permitted the unveiling of key features of the conformational equilibrium that would have otherwise remained unobserved.

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Section: Introductionmentioning

confidence: 99%

Conformational Plasticity in Glycomimetics: Fluorocarbamethyl‐L‐idopyranosides Mimic the Intrinsic Dynamic Behaviour of Natural Idose Rings

Unione

Díaz

et al. 2015

Chemistry A European J

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“…This result suggesting that the C-glycosides possesses foam enhancing and stabilizing effect in the presence of an anionic surfactant(Figure 15). the field of C-glycoside chemistry has received increasingly growing attention in the past four decades 187. Different synthetic approaches are currently available for the synthesis of Cglycosides from various functionalized sugar derivatives.…”

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confidence: 99%

Recent developments in β-C-glycosides: synthesis and applications

Lalitha

Muthusamy

Prasad

et al. 2015

Carbohydrate Research

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“…However, this approach is still in its infancies, as few examples are known that describe the synthesis of 5a‐fluorinated carba‐pyranoses and their biological activity (reviewed in ref. ).…”

Section: Introductionmentioning

confidence: 97%

Fluoro‐Carba‐Sugars are Glycomimetic Activators of the glmS Ribozyme

Matzner

Schüller

Seitz

et al. 2017

Chemistry A European J

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The glmS ribozyme is a bacterial gene-regulating riboswitch that controls cell wall synthesis, depending on glucosamine-6-phosphate as a cofactor. Due to the presence of this ribozyme in several human pathogen bacteria (e.g., MRSA, VRSA), the glmS ribozyme represents an attractive target for the development of artificial cofactors. The substitution of the ring oxygen in carbohydrates by functionalized methylene groups leads to a new generation of glycomimetics that exploits distinct interaction possibilities with their target structure in biological systems. Herein, we describe the synthesis of mono-fluoro-modified carba variants of α-d-glucosamine and β-l-idosamine. (5aR)-Fluoro-carba-α-d-glucosamine-6-phosphate is a synthetic mimic of the natural ligand of the glmS ribozyme and is capable of effectively addressing its unique self-cleavage mechanism. However, in contrast to what was expected, the activity is significantly decreased compared to its non-fluorinated analog. By combining self-cleavage assays with the Bacillus subtilis and Staphylococcus aureus glmS ribozyme and molecular docking studies, we provide a structure-activity relationship for fluorinated carba-sugars.

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Fluoro-C-glycosides and fluoro-carbasugars, hydrolytically stable and synthetically challenging glycomimetics

Cited by 97 publications

References 50 publications

Conformational Plasticity in Glycomimetics: Fluorocarbamethyl‐L‐idopyranosides Mimic the Intrinsic Dynamic Behaviour of Natural Idose Rings

Conformational Plasticity in Glycomimetics: Fluorocarbamethyl‐L‐idopyranosides Mimic the Intrinsic Dynamic Behaviour of Natural Idose Rings

Recent developments in β-C-glycosides: synthesis and applications

Fluoro‐Carba‐Sugars are Glycomimetic Activators of the glmS Ribozyme

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