Photocyclisation d'hydroxyalkyl glycosides en orthoesters glycosidiques

A free-radical cyclization process makes glycosidic orthoester structures readily available in a one-pot procedure.     

Selectivity among two lectins: probing the effect of topology, multivalency and flexibility of "clicked" multivalent glycoclusters

The design of multivalent glycoconjugates has been developed over the past decades to obtain high-affinity ligands for lectin receptors. While multivalency frequently increases the affinity of a ligand for its lectin through the so-called "glycoside cluster effect", the binding profiles towards different lectins have been much less investigated. We have designed a series of multivalent galactosylated glycoconjugates and studied their binding properties towards two lectins, from plant and bacterial origins, to determine their potential selectivity. The synthesis was achieved through copper(I)-catalysed azide-alkyne cycloaddition (CuAAC) under microwave activation between propargylated multivalent scaffolds and an azido-functionalised carbohydrate derivative. The interactions of two galactose-binding lectins from Pseudomonas aeruginosa (PA-IL) and Erythrina cristagalli (ECA) with the synthesized glycoclusters were studied by hemagglutination inhibition assays (HIA), surface plasmon resonance (SPR) and isothermal titration microcalorimetry (ITC). The results obtained illustrate the influence of the scaffold's geometry on the affinity towards the lectin and also on the relative potency in comparison with a monovalent galactoside reference probe.     

Synthesis of dodecavalent fullerene-based glycoclusters and evaluation of their binding properties towards a bacterial lectin

Multivalency is playing a major role in biological processes and particularly in lectin-carbohydrate interactions. The design of high-affinity ligands of lectins should provide molecules capable of interfering with these biological processes and potentially inhibit bacterial or viral infections. Azide-alkyne "click" chemistry was applied to the synthesis of dodecavalent fullerene-based glycoclusters. The conjugation could be efficiently performed from alkyne or azide functions on either partners (i.e. hexakis-fullerene adduct or glycoside). PA-IL is a bacterial lectin from the opportunistic pathogen Pseudomonas aeruginosa and is involved in the recognition of glycoconjugates on human tissues. The glycoclusters obtained were evaluated as ligands of PA-IL and for their potential for competing with its binding to glycosylated surfaces. The affinities measured by hemagglutination inhibition assay (HIA), enzyme-linked lectin assay (ELLA), and surface plasmon resonance (SPR) displayed a significant "glycoside cluster effect" with up to a 12,000-fold increase in binding when comparing a monovalent carbohydrate reference probe with a dodecavalent fullerene-based glycocluster, albeit with some differences depending on the analytical technique.     

Multiplexed binding determination of seven glycoconjugates for Pseudomonas aeruginosa lectin I (PA-IL) using a DNA-based carbohydrate microarray

The binding of seven multivalent glycoconjugates displaying linear or antenna-like structures and different electronic environments were evaluated towards PA-IL on a DNA-based carbohydrate microarray. The affinity can be modulated by the charge and the topology of the galactosylated derivatives.     

C-Glycopyranosyl-1,4-benzoquinones and -hydroquinones opening access to C-glycosylated analogs of vitamin E

2-(Per-O-acetyl-β-d-glycopyranosyl)-1,4-dimethoxybenzenes led to C-glycosyl-hydroquinones suitable for preparing C-glycosylated analogs of vitamin E, having the sugar moiety free or acetylated.     

Radical-Mediated Halogenations of Anomerically N-Substituted Glucopyranosyl Derivatives

Abstract

Reactions of acetylated N-aryl-D-glucosylamines with N-bromosuccinimide-benzoyl peroxide or with sulfuryl chloride-azoisobutyronitrile gave aromatic halo derivatives. The corresponding N-acetylated compounds were mostly inert towards halogenation. Bromination of acetylated cellobiosylpiperidine resulted in the formation of acetobromocellobiose, while the acetylated 2,6,8-trichloro-9-(β-D-glucopyranosyl)-purine was transformed into its 5′-bromo derivative. In contrast, peracetylated glucopyranosyl isothiocyanate or azides, when treated by N-bromosuccinimide under free-radical conditions, essentially undergo an initial homolysis of the anomeric C-H bond which is faster for β-anomers. This initiates a new, simple and efficient free-radical transformation of such sugar azides into an unprecedented brornimino lactone (92% isolated yield).