Synthesis and glycosidase inhibition potency of all- trans substituted 1- C -perfluoroalkyl iminosugars

Massicot, Fabien; Plantier‐Royon, Richard; Vasse, Jean‐Luc; Behr, Jean‐Bernard

doi:10.1016/j.carres.2018.05.004

Cited by 15 publications

(3 citation statements)

References 75 publications

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“…Following a similar sequence, Behr and co‐workers recently described the synthesis of arabino ‐configured perfluoroalkyl DMDP analogs, by using an organomagnesium derivative as the nucleophile (Scheme 20). [59] By using a l ‐xylose precursor 65 , a d ‐ arabino ‐configured nitrone 66 was obtained and used as the starting material for the addition reaction of a perfluoroalkyl Grignard reagent. The products obtained arose from the nucleophilic attack from the less hindered Re face (i.e., 67 , 68 ).…”

Section: Perfluoroalkyl‐substituted Iminosugarsmentioning

confidence: 99%

Approaches to the Synthesis of Perfluoroalkyl‐Modified Carbohydrates and Derivatives: Thiosugars, Iminosugars, and Tetrahydro(thio)pyrans

Uhrig

Flores

Postigo

2021

Chemistry A European J

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Fluoroalkyl-substituted carbohydrates play relevant roles in diverse areas such as supramolecular chemistry, glycoconjugation, liquid crystals, and surfactants, with direct applications as wetting, antifreeze, and coating agents. In light of these promising applications, new methodologies for the late-stage incorporation of fluoroalkyl R F groups into carbohydrates and derivatives are herein presented as they are relevant to the synthetic carbohydrate community. Previously reviewed protocols for the installation of R F groups onto carbohydrates and derivatives will be succinctly summarized in the light of the new achievements. Fluoroalkylsubstituted iminosugars, on the other hand, are also interesting glycomimetic derivatives with prominent roles as glycosidases and glycosyltransferases inhibitors, as has recently been demonstrated. Also, they positively contribute to the study of sugar-protein interactions and enzyme mechanisms. New advances in the syntheses of fluoroalkyl-substituted iminosugars will also be presented here.

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Section: Perfluoroalkyl‐substituted Iminosugarsmentioning

confidence: 99%

Approaches to the Synthesis of Perfluoroalkyl‐Modified Carbohydrates and Derivatives: Thiosugars, Iminosugars, and Tetrahydro(thio)pyrans

Uhrig

Flores

Postigo

2021

Chemistry A European J

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“…Of note, the impact of fluorine atoms on the glycosidase inhibition potency still remains not predictable, because fluorination might deeply influence the hydrophobicity or the electron density of iminosugars, as well as the pKa of the amine function. Behr et al have recently reported the synthesis of iminosugars that bear a perfluoroalkyl chain at the pseudoanomeric position, where the key synthetic step is the stereoselective nucleophilic addition of fluorinated Grignard reagents onto cyclic nitrone 7 (Figure ).…”

Section: Endocyclic Oxygen Replacementmentioning

confidence: 99%

“…Two fluorinated iminosugars with a perfluoropropyl (Figure ; compound 9a ) or a perfluorobutyl chain (Figure ; compound 9b ) were tested against a panel of glycosidases: while the introduction of a C 4 F 9 group (compound 9b ) resulted in an inactive compound for enzyme binding, the presence of a C 3 F 7 chain (compound 9a ) afforded potent and selective inhibition of bovine liver α‐fucosidase, yeast α‐glucosidase from Saccharomyces cerevisiae and almond β‐glucosidase …”

Section: Endocyclic Oxygen Replacementmentioning

confidence: 99%

Design and synthesis of glycomimetics: Recent advances

Tamburrini

Colombo

Bernardi

2019

Medicinal Research Reviews

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In the past few decades, our understanding of glycan information‐encoding power has notably increased, thus leading to a significant growth also in the design and synthesis of glycomimetic probes. Combining data from multiple analytical sources, such as crystallography, nuclear magnetic resonance spectroscopy, and other biophysical methods (eg, surface plasmon resonance and carbohydrate microarrays) has allowed to shed light on the key interaction events between carbohydrates and their protein‐targets. However, the low metabolic stability of carbohydrates and their high hydrophilicity, which translates in low bioavailability, undermine their development as drugs. In this framework, the design of chemically modified analogues (called carbohydrate mimics or glycomimetics) appears as a valid alternative for the development of therapeutic agents. Glycomimetics, as structural and functional mimics of carbohydrates, can replace the native ligands in the interaction with target proteins, but are designed to show enhanced enzymatic stability and bioavailability and, possibly, an improved affinity and selectivity toward the target. In the present account, we specifically focus on the most recent advances in the design and synthesis of glycomimetics. In particular, we highlight the efforts of the scientific community in the development of straightforward synthetic procedures for the preparation of sugar mimics and in their preliminary biological evaluation.

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