Reactions of Difluoroenoxysilanes with Glycosyl Donors: Synthesis of Difluoro-C-glycosides and Difluoro-C-disaccharides

Berber, Hatice; Brigaud, Thierry; Lefebvre, Olivier; Plantier‐Royon, Richard; Portella, Charles

doi:10.1002/1521-3765(20010216)7:4<903::aid-chem903>3.0.co;2-m

Cited by 46 publications

(33 citation statements)

References 30 publications

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“…The recognition of the difluoromethylene group as isopolar and bioisosteric to oxygen194 triggered interest in the synthesis of difluoro‐substituted C ‐glycosides 195. In this context, Portella and co‐workers reported BF 3 · Et 2 O‐mediated reactions between difluoroenoxysilanes196 and tri‐ O ‐acetyl‐ D ‐glucal ( 5 ) to afford difluoro‐ C ‐glycosides (Scheme ) 196,197. Regardless of the starting difluoroenoxysilane employed, the reaction gave mixtures of anomers with diastereomeric ratios similar to those already reported by Fraser‐Reid and co‐workers for the non‐fluorinated (hydrogenated) analogues 190a…”

Section: Other Nucleophiles In the Frsupporting

confidence: 67%

Recent Developments in the Ferrier Rearrangement

et al. 2013

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Glycals (1,2‐unsaturated, cyclic carbohydrate derivatives) readily undergo (catalyzed) substitution reactions at C‐1 accompanied by allylic rearrangement. This reaction, currently named Ferrier rearrangement, or the Ferrier I reaction, has established itself as a useful synthetic tool for carbohydrate transformations. By means of this reaction, glycals can be converted into highly useful 2,3‐unsaturated glycosides. This review summarizes recent developments in the use of promoters for the Ferrier rearrangement of O‐, N‐, C‐ and S‐nucleophiles with glycals.

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Section: Other Nucleophiles In the Frsupporting

confidence: 67%

Recent Developments in the Ferrier Rearrangement

et al. 2013

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“…There is indeed greater conformational flexibility observed, but it is evidently not as detrimental to binding as would be expected. Modification of the linked carbon atom with one or two fluorine atoms has also been used to enhance the electronegativity of the bridging unit and further limit its conformational flexibility, yet retain the benefit of the metabolically stable C -glycoside [100,101,102]. C -Glycosides have been used in the glycomimetic design of numerous inhibitors, including sLe x [96], GM 4 ganglioside [103], galactopyranosides [104,105], mannopyranosides [105,106,107], fucopyranosides [105,108,109], and pseudoglycopeptides [106], among others.…”

Section: Glycomimetic Design—strategies To Improve Pharmacokineticmentioning

confidence: 99%

Strategies for the Development of Glycomimetic Drug Candidates

Hevey

2019

Pharmaceuticals

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Carbohydrates are a structurally-diverse group of natural products which play an important role in numerous biological processes, including immune regulation, infection, and cancer metastasis. Many diseases have been correlated with changes in the composition of cell-surface glycans, highlighting their potential as a therapeutic target. Unfortunately, native carbohydrates suffer from inherently weak binding affinities and poor pharmacokinetic properties. To enhance their usefulness as drug candidates, ‘glycomimetics’ have been developed: more drug-like compounds which mimic the structure and function of native carbohydrates. Approaches to improve binding affinities (e.g., deoxygenation, pre-organization) and pharmacokinetic properties (e.g., limiting metabolic degradation, improving permeability) have been highlighted in this review, accompanied by relevant examples. By utilizing these strategies, high-affinity ligands with optimized properties can be rationally designed and used to address therapies for novel carbohydrate-binding targets.

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“…These conformational changes can arise from a combination of larger atom (e.g., S, Se) or loss of the exo-anomeric effect due to replacement with a less electronegative substituent (e.g., C). This conformational flexibility can potentially be reduced through the addition of steric bulk that constrains the molecule to a particular conformation [52,53,54], or by the addition of electronegative atoms such as fluorine to C -glycosides to reestablish the electron-withdrawing character of the anomeric substituent [51,55,56,57,58].…”

Section: Modifications To the O-glycoside Linkagementioning

confidence: 99%

Bioisosteres of Carbohydrate Functional Groups in Glycomimetic Design

Hevey

2019

Biomimetics

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The aberrant presentation of carbohydrates has been linked to a number of diseases, such as cancer metastasis and immune dysregulation. These altered glycan structures represent a target for novel therapies by modulating their associated interactions with neighboring cells and molecules. Although these interactions are highly specific, native carbohydrates are characterized by very low affinities and inherently poor pharmacokinetic properties. Glycomimetic compounds, which mimic the structure and function of native glycans, have been successful in producing molecules with improved pharmacokinetic (PK) and pharmacodynamic (PD) features. Several strategies have been developed for glycomimetic design such as ligand pre-organization or reducing polar surface area. A related approach to developing glycomimetics relies on the bioisosteric replacement of carbohydrate functional groups. These changes can offer improvements to both binding affinity (e.g., reduced desolvation costs, enhanced metal chelation) and pharmacokinetic parameters (e.g., improved oral bioavailability). Several examples of bioisosteric modifications to carbohydrates have been reported; this review aims to consolidate them and presents different possibilities for enhancing core interactions in glycomimetics.

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Reactions of Difluoroenoxysilanes with Glycosyl Donors: Synthesis of Difluoro-C-glycosides and Difluoro-C-disaccharides

Cited by 46 publications

References 30 publications

Recent Developments in the Ferrier Rearrangement

Recent Developments in the Ferrier Rearrangement

Strategies for the Development of Glycomimetic Drug Candidates

Bioisosteres of Carbohydrate Functional Groups in Glycomimetic Design

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