Yann Bourdreux

Iron(III) chloride-tandem catalysis for a one-pot regioselective protection of glycopyranosides.

Tandem catalysis by using iron(III) chloride hexahydrate leads to carbohydrate building blocks displaying an orthogonal protecting group pattern as illustrated by the regioselective protection of trehalose and maltose disaccharides.

Diastereoselective syntheses of α-amino-β-hydroxyesters precursors of the ribosyl-diazepanone core of the liposidomycins

The diastereoselective syntheses of the O -protected ribosyl-β-hydroxy-α-amino esters 3 and 4 , precursors of α-ribosyl-diazepanone core analogues of the liposidomycins, respectively, from the β-ketoesters 5 and 6 are described. The anti relationship between the two adjacent aminated and hydroxylated carbons was controlled by sequential hydrogenation of the β-ketoesters in the presence of chiral ruthenium catalysts and electrophilic amination of the resulting β-hydroxyesters.

Simplified Deoxypropionate Acyl Chains for Mycobacterium tuberculosis Sulfoglycolipid Analogues: Chain Length is Essential for High Antigenicity

The longer, the better: Increasing the lengths of the 1,3-methyl-branched fatty acyl chain units in mycobacterial diacylated sulfoglycolipid (Acyl2 SGL) analogues led to dramatic improvements in their antigenic properties and gave products more potent than the natural antigen Acyl2 SGLs.

Synthesis of a Mycobacterium tuberculosis tetra-acylated sulfolipid analogue and characterization of the chiral acyl chains using anisotropic NAD 2D-NMR spectroscopy.

Tetra-O-acylated sulfolipids are metabolites found in the cell wall of Mycobacterium tuberculosis, the causative agent of tuberculosis. Their role in pathogenesis remains, however, undefined. Here we describe a novel access to model tetra-O-acylated trehalose sulfate derivatives having simple acyl chains. The trehalose core was regioselectively protected using a tandem procedure with catalytic iron(III) chloride hexahydrate and further desymmetrized. Model chiral fatty acids, prepared by a zinc-mediated cross-coupling, were incorporated into the trehalose core. The enantiomeric excess of the chiral fatty acids has been measured by natural abundance deuterium (NAD) 2D-NMR spectroscopy in a polypeptide based chiral liquid crystal. The synthetic approach established for the model compounds can easily be developed for the preparation of other analogues and natural sulfolipids.

Characterization of Protonated Model Disaccharides from Tandem Mass Spectrometry and Chemical Dynamics Simulations

The fragmentation mechanisms of prototypical disaccharides have been studied herein by coupling tandem mass spectrometry (MS) with collisional chemical dynamics simulations. These calculations were performed by explicitly considering the collisions between the protonated sugar and the neutral target gas, which led to an ensemble of trajectories for each system, from which it was possible to obtain reaction products and mechanisms without pre-imposing them. The β-aminoethyl and aminopropyl derivatives of cellobiose, maltose, and gentiobiose were studied to observe differences in both the stereochemistry and the location of the glycosidic linkage. Chemical dynamics simulations of MS/MS and MS/MS/MS were used to suggest some primary and secondary fragmentation mechanisms for some experimentally observed product ions. These simulations provided some new insights into the fundamentals of the unimolecular dissociation of protonated sugars under collisional induced dissociation conditions.

Chapter 7:Recent results in synthetic glycochemistry with iron salts at Orsay-Gif

This review particularly emphasizes synthetic applications resulting from cascade or one-pot transformations and a glycosylation reaction promoted by ferric salts. These easy to handle, cheap and environment-friendly salts have been examined for their ability to induce, as a Lewis acid, fast carbohydrate-based modifications in our laboratories at Orsay and Gif sur Yvette. A short synthetic route to the dihydropyran framework of anti-influenza constructs is reported by coupling the Petasis three-component condensation to an iron(iii)-promoted one-pot cascade of deprotection – C–C double bond isomerization – cyclization - oxazoline formation. We also show that iron(iii) chloride hexahydrate is most appropriate to catalyze a one-pot regioselective protection of mono- and disaccharides. This iron(iii) catalysis renders multi-step routes, such as chemical oligosaccharide syntheses, faster. In the last section, we report a catalytic glycosylation method particularly simple and straightforward leading to the important β-d-GlcNAc motif, in which the more electrophilic iron(iii) triflate activates the readily available peracetate of N-acetyl-β-d-glucosamine. This glycosylation does not necessarily require the formation of the mandatory oxazolinium intermediate.