Glycoside Mimics from Glycosylamines: Recent Progress

Nicolas, Cyril; Martin, Olivier R.

doi:10.3390/molecules23071612

Cited by 29 publications

(23 citation statements)

References 105 publications

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“…Our first attempts at cyclization using bulky bases such as t ‐BuOK or Et 3 N in THF failed. Alternatively cleavage of the sulfinyl group (HCl in MeOH) and subsequent ring closure promoted by a basic resin was also unsuccessful [12g,13,26] . The problem could be solved using an excess of sodium hydride (NaH, 3 equiv.)…”

Section: Resultsmentioning

confidence: 99%

Stereospecific Synthesis of Glycoside Mimics Through Migita‐Kosugi‐Stille Cross‐Coupling Reactions of Chemically and Configurationally Stable 1‐C‐Tributylstannyl Iminosugars

Jaszczyk

Pannecoucke

et al. 2020

Adv Synth Catal

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A process for the de novo synthesis of imino‐C‐glycosides is described. The methodology is based on the reaction of 1‐C‐stannylated iminosugars with various electrophiles under the conditions of Migita‐Kosugi‐Stille cross‐couplings, which gives 1‐C‐substituted iminosugar derivatives in a stereoretentive process. The required iminoglycosyl stannanes are obtained by way of the highly stereoselective addition of tributylstannyllithium to (SR)‐ or (SS)‐N‐tert‐butanesulfinyl glycosylamines, followed by an activation cyclization sequence. Most interestingly, the methodology is tunable: the configuration of the tin adduct is controlled exclusively by the tert‐butanesulfinyl auxiliary, thus giving access after ring formation to ‘α’‐configured or ‘β’‐configured iminoglycosyl stannanes. With the subsequent stereoretentive C−C bond‐forming process, the methodology allows the synthesis of pseudo anomers of imino‐C‐glycosyl compounds in a controlled fashion.

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Section: Resultsmentioning

confidence: 99%

Stereospecific Synthesis of Glycoside Mimics Through Migita‐Kosugi‐Stille Cross‐Coupling Reactions of Chemically and Configurationally Stable 1‐C‐Tributylstannyl Iminosugars

Jaszczyk

Pannecoucke

et al. 2020

Adv Synth Catal

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“…However, glycomimetics still have limitations as drug candidates or biological probes. For example, in the most common class of glycomimetics, imino sugars, bound glycosides are unstable because of variable N, O-acetal function [137]. Furthermore, some glycomimetic synthesis reactions are tremendously complicated due to their natural valency, topology, and density of carbohydrate presentation [138].…”

Section: Glycan Mimetics From Natural Productsmentioning

confidence: 99%

Glycan Mimetics from Natural Products: New Therapeutic Opportunities for Neurodegenerative Disease

et al. 2019

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Neurodegenerative diseases (NDs) affect millions of people worldwide. Characterized by the functional loss and death of neurons, NDs lead to symptoms (dementia and seizures) that affect the daily lives of patients. In spite of extensive research into NDs, the number of approved drugs for their treatment remains limited. There is therefore an urgent need to develop new approaches for the prevention and treatment of NDs. Glycans (carbohydrate chains) are ubiquitous, abundant, and structural complex natural biopolymers. Glycans often covalently attach to proteins and lipids to regulate cellular recognition, adhesion, and signaling. The importance of glycans in both the developing and mature nervous system is well characterized. Moreover, glycan dysregulation has been observed in NDs such as Alzheimer’s disease (AD), Huntington’s disease (HD), Parkinson’s disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). Therefore, glycans are promising but underexploited therapeutic targets. In this review, we summarize the current understanding of glycans in NDs. We also discuss a number of natural products that functionally mimic glycans to protect neurons, which therefore represent promising new therapeutic approaches for patients with NDs.

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“…In general, representatives of this substance class are known as ligands for carbohydrate-processing enzymes (CPEs), as they interact with the active site of the respective protein as mimics of the natural substrate [ 7 , 8 , 9 , 10 ]. Iminosugar-based structures are versatile probes and have been used in several different applications as inhibitors, [ 11 , 12 ] therapeutics [ 8 , 9 , 10 ] and probes for activity-based protein profiling [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

N-Alkylated Iminosugar Based Ligands: Synthesis and Inhibition of Human Lysosomal β-Glucocerebrosidase

et al. 2020

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The scope of a series of N-alkylated iminosugar based inhibitors in the d-gluco as well as d-xylo configuration towards their interaction with human lysosomal β-glucocerebrosidase has been evaluated. A versatile synthetic toolbox has been developed for the synthesis of N-alkylated iminosugar scaffolds conjugated to a variety of terminal groups via a benzoic acid ester linker. The terminal groups such as nitrile, azide, alkyne, nonafluoro-tert-butyl and amino substituents enable follow-up chemistry as well as visualisation experiments. All compounds showed promising inhibitory properties as well as selectivities for β-glucosidases, some exhibiting activities in the low nanomolar range for β-glucocerebrosidase.

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Glycoside Mimics from Glycosylamines: Recent Progress

Cited by 29 publications

References 105 publications

Stereospecific Synthesis of Glycoside Mimics Through Migita‐Kosugi‐Stille Cross‐Coupling Reactions of Chemically and Configurationally Stable 1‐C‐Tributylstannyl Iminosugars

Stereospecific Synthesis of Glycoside Mimics Through Migita‐Kosugi‐Stille Cross‐Coupling Reactions of Chemically and Configurationally Stable 1‐C‐Tributylstannyl Iminosugars

Glycan Mimetics from Natural Products: New Therapeutic Opportunities for Neurodegenerative Disease

N-Alkylated Iminosugar Based Ligands: Synthesis and Inhibition of Human Lysosomal β-Glucocerebrosidase

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