André Lubineau

Improved synthesis of glycosylamines and a straightforward preparation of N-acylglycosylamines as carbohydrate-based detergents.

D-Glucose, D-galactose, lactose, cellobiose, and maltose yield quantitatively the corresponding glycosylamine when treated at 42 degrees C for 36 h with a commercial aqueous solution of ammonia in the presence of one equivalent of ammonium hydrogen carbonate. After lyophilisation, the residue (i.e., the pure glucosylamine) was dissolved in a mixture of ethanol and water, and treated with acyl chlorides to afford in a few minutes N-acylglucosylamines. Micellar properties of these amphiphilic derivatives were determined.

WATER AS SOLVENT IN ORGANIC SYNTHESIS

Organic reactions using water as solvent are reviewed with a focus on pericyclic reactions, carbonyl additions, stoichiometric organometallic reactions, oxidations and reductions which show an unusual outcome in terms of reactivity and selectivity compared with those performed in organic solvent. The advantages of using water as a solvent are discussed and related to the hydrophobic effects and the hydrogen-bonding ability of water with a special emphasis on its very high cohesive energy density which strongly favors organic reactions having a negative activation volume.

ACCELERATION IN WATER OF THE BAYLIS-HILLMAN REACTION

Abstract DABCO-catalyzed coupling reaction of benzaldehyde with acrylonitrile was greatly accelerated in water compared to usual organic solvents. The reaction was even more accelerated by adding lithium or sodium iodide in the aqueous medium. Other structured solvents also enhanced the reaction, but to a smaller extent.

Water-promoted organic reactions. Aldol reaction of silyl enol ethers with carbonyl compounds under atmospheric pressure and neutral conditions

Summary As a consequence of the hydrophobic effect, the reaction between silyl enol ethers and aldehydes are shown to proceed without a catalyst in aqueous solution and neutral conditions providing crossed-aldol products,with a syn selectivity, as under pressure, that is the reverse in comparison with the acid catalysed reaction. With α, β-unsaturated aldehydes, 1,2- and 1,4-addition were observed, whereas with α, β-unsaturated ketones, only 1,4-addition occurred.

New accesses to l-iduronyl synthons

(PhS)3CLi adds with a total l-ido selectivity onto 3-O-benzyl-1,2-O-isopropylidene-α-d-xylo-dialdose 2, opening the way to the most efficient preparation of 1,2,4-tri-O-acetyl-3-O-benzyl-l-iduronyl synthon 8. Alternatively, in view of combinatorial syntheses, aldehyde 2 allows a good access to vinylic l-ido and d-gluco synthons which may be converted into uronic acid by a sequence involving a new aldehyde oxidation by m-CPBA in aqueous solution.

Regioselective sulfation of galactose derivatives through the stannylene procedure. New synthesis of the 3′-O-sulfated Lewisa trisaccharide

Free or 6-protected β-D-galactopyranosides afforded, in excellent yields, the 3′-O-sulfate as the only product through the stannylene procedure. This methodology was successfully applied to the synthesis of the 3′-O- sulfated Lewisa trisaccharide, an oligosaccharide reported as ligand of E- and L-selectins.

Heparan Sulfate Mimicry A SYNTHETIC GLYCOCONJUGATE THAT RECOGNIZES THE HEPARIN BINDING DOMAIN OF INTERFERON-γ INHIBITS THE CYTOKINE ACTIVITY

Cell-associated heparan sulfate (HS) is endowed with the remarkable ability to bind numerous proteins. As such, it represents a unique system that integrates signaling from circulating ligands with cellular receptors. This polysaccharide is extraordinary complex, and examples that define the structure-function relationship of HS are limited. In particular, it remains difficult to understand the structures by which HS interact with proteins. Among them, interferon-γ (IFNγ), a dimeric cytokine, binds to a complex oligosaccharide motif encompassing a N-acetylated glucosamine-rich domain and two highly sulfated sequences, each of which binds to one IFNγ monomer. Based on this template, we have synthesized a set of glycoconjugate mimetics and evaluated their ability to interact with IFNγ. One of these molecules, composed of two authentic N-sulfated octasaccharides linked to each other through a 50-Å-long spacer termed 2O10, displays high affinity for the cytokine and inhibits IFNγ-HS binding with an IC50 of 35–40 nm. Interestingly, this molecule also inhibits the binding of IFNγ to its cellular receptor. Thus, in addition to its ability to delocalize the cytokine from cell surface-associated HS, this compound has direct anti-IFNγ activity. Altogether, our results represent the first synthetic HS-like molecule that targets a cytokine, strongly validating the HS structural determinants for IFNγ recognition, providing a new strategy to inhibit IFNγ in a number of diseases in which the cytokine has been identified as a target, and reinforcing the view that it is possible to create”tailor-made“sequences based on the HS template to isolate therapeutic activities.

Glyco-organic substrates in organic synthesis. Preparation of a water soluble butadienyl-ether and its use in aqueous cycloaddition.

Abstract A chiral water-soluble butadienyl-ether containing free glucose as hydrophilic moiety was synthesized and used in aqueous cycloaddition reaction with methacrolein to afford through pure endo transition state, only two diastereoisomers from which the sugar could be removed by enzymatic hydrolysis.

Hetero Diels-Alder reaction in water. Synthesis of α-hydroxy-γ-lactones

Abstract The hetero Diels-Alder reaction of cyclopentadiene or cyclohexadiene with aqueous solution of glyoxylic acid produces α-hydroxy-γ-lactones arising from the rearrangement of the cycloadducts.

Thioglycosides as Potential Glycosyl Donors in Electrochemical Glycosylation Reactions. Part 1: Their Preparation and Reactivity Toward Simple Alcohols.

Abstract Constant potential electrolysis of several glycosyl donors such as substituted phenyl 2,3,4,6-tetra-O-acetyl, benzoyl or benzyl-1-thio-β-D-gluco or galactopyranosides in dry acetonitrile in the presence of various primary, secondary or tertiary alcohols performed in an undivided cell, gave preferentially β-linked saccharides in moderate to good yields according to the nature of the protective groups on the sugar moiety. 2-Deoxy-2-phthalimido-1-thio-β-D-gluco derivatives gave the β-glucosides selectively in excellent yields. It was found, as expected, that substitution of the phenyl group with methoxy or methyl radicals facilitates the electrochemical glycosylation reaction by lowering the oxidation potentials of the corresponding thioglycosides.