Vincent Ferrières

Recent knowledge and innovations related to hexofuranosides: structure, synthesis and applications

Hexofuranosides are widely spread in nature, and notably in numerous pathogenic microorganisms. This particular five-membered ring for hexosides leads to novel biological properties and, as usual in glycochemistry, to completely different reactivity and selectivity. Far from being exhaustive, this review will first focus on the structure of the oligosaccharidic part of hexofuranosyl conjugates found in natural sources. Original syntheses will then be presented, stressing more particularly on the development of chemical and chemo-enzymatic tools for the access to 1,2-trans or 1,2-cis linkages. Finally, innovative applications related to biological, chemical and physicochemical fields for both natural and synthetic hexofuranosyl compounds will be described.

A new synthesis of O-glycosides from totally O-unprotected glycosyl donors

Abstract O-Glycosidation of the totally O-unprotected aldoses (D-glucose, D-galactose and D-mannose) and D-fructose in THF or 1,4-dioxane using anhydrous FeCl3 as promoter afforded either aldofuranosides 1, 3, 4 in good overall yields or exclusively β-D-fructopyranosides 7. Conversely α-D-aldopyranosides 2, 5 and 6 were obtained respectively from D-glucose, D-mannose and N-acetyl-D-glucosamine when the reactions were performed in the presence of BF3.OEt2 under ultrasonication.

A convenient synthesis of alkyl d-glycofuranosiduronic acids and alkyl d-glycofuranosides from unprotected carbohydrates

Abstract O -Glycosylation of a variety of long chain alcohols with totally unprotected uronic acids ( d -glucuronic and d -galacturonic acids) and neutral carbohydrates ( d -glucose, d -galactose, d -mannose and d -glucofuranurono-6,3-lactone), performed in heterogeneous media and promoted by Lewis acids (ferric chloride or boron trifluoride diethyl etherate), afforded alkyl d -glycofuranosiduronic acids and alkyl d -glycofuranosides, respectively, in high yields. Both chemoselectivity and anomeric stereoselectivity were enhanced by complexing agents, i.e. calcium or barium chloride.

A General and Diastereoselective Synthesis of 1,2-cis-Hexofuranosides from 1,2-trans-Thiofuranosyl Donors

The general formation of 1,2-trans-thioglycofuranosides derived from D-galactose, D-glucose and D-mannose was readily accomplished starting from the corresponding alkyl glycofuranosides via per-O-acetyl-hexofuranoses as key synthons. Glycosidation of ethyl or phenyl perbenzylated 1,2-trans-thiofuranosides afforded disaccharides containing a nonreducing 1,2-cis-hexofuranosyl unit, i.e. α-D-galactosyl, α-D-glucosyl or β-D-mannosyl, with interesting diastereoselectivities. Activation of the thiofuranosyl donors was performed by N-iodosuccinimide and a catalytic amount of tin(II) trifluoromethanesulfonate.

Recent Progress in the Field of β-(1,3)-Glucans and New Applications

β-(1,3)-Glucans are widely distributed within microorganisms or seaweeds in which they act as membrane components or for energy storage, respectively. Since these glucans are not biosynthesized by mammals, they are likely to activate the immune system of their host. Since the discovery of their positive involvement as immunomodulator agents, numerous studies were published all around the glycosciences. These works deal with purification procedures, analytical chemistry, synthetic processes, chemical modification of the natural polysaccharides, determination of their physicochemical properties, and assessment of their biological and medicinal effects through in vitro and in vivo studies. This article aims at presenting some recent results linked to β-(1,3)-glucans through two closely connected points of view, i.e. biology and chemistry. Biological aspects will be focused more particularly on discovery of some receptors present on immunocompetent cells and scope and limitations of chemical synthesis and/or modifications will be described. Moreover, this paper will also introduce some new chemo-enzymatic synthetic methods using wild-type or mutant glycosidases and will be extended to novel opportunities of applications of β-(1,3)-glucans in nanotechnology resulting from a better understanding of their self-assembling propensity in aqueous media.

Natural Glycans and Glycoconjugates as Immunomodulating Agents

Covering: up to the end of 2010 This review focuses on recent discoveries performed in the field of glycans and related glycoconjugates that have demonstrated immunomodulatory activities. Their tremendous potential for application, as well as some limitations, are also described.

Specific and non-specific enzymes for furanosyl-containing conjugates: biosynthesis, metabolism, and chemo-enzymatic synthesis.

There is no doubt now that the synthesis of compounds of varying complexity such as saccharides and derivatives thereof continuously grows with enzymatic methods. This review focuses on recent basic knowledge on enzymes specifically involved in the biosynthesis and degradation of furanosyl-containing polysaccharides and conjugates. Moreover, and when possible, biocatalyzed approaches, alternative to standard synthesis, will be detailed in order to strengthen the high potential of these biocatalysts to go further with the preparation of rare furanosides. Interesting results will be also proposed with chemo-enzymatic processes based on nonfuranosyl-specific enzymes.

Enzymatic synthesis of oligo-D-galactofuranosides and L-arabinofuranosides: from molecular dynamics to immunological assays

D-Galactofuranosyl-containing conjugates are ubiquitous in many pathogenic microorganisms, but completely absent from mammals. As they may constitute interesting pharmacophores, recent works have been dedicated to their preparation. Besides well-reported chemical procedures, enzymatic approaches are still limited, mainly due to the lack of the corresponding biocatalysts. Based on the similarity between chemical structures, the arabinofuranosyl hydrolase Araf51 from Clostridium thermocellum was expected to recognize both the L-Araf motif and its D-Galf analogue. Molecular dynamics and STD-NMR were firstly used to confirm this hypothesis and increase our knowledge of the active site. Interestingly, this arabinofuranosidase was not only able to hydrolyze galactosyl derivatives, but was also really efficient in catalyzing oligomerisations using p-nitrophenyl furanosides as donors. The structures of the products obtained were determined using mass spectrometry and NMR. Amongst them, all the possible regioisomers of di-arabino and -galactofuranosides were synthesized, and the ratio of each regioisomer was easily tuned with respect to the reaction time. Especially, the galactofuranobioside displaying the biologically relevant sequence beta-D-Galf-(1,6)-beta-D-Galf was enzymatically prepared for the first time. All fractions going from di- to penta-arabino- and galactofuranosides were tested for their ability in eliciting the production of TNF-alpha. Interesting immunological properties were observed with arabinofuranosides as short as three sugar residues.

Amphitropic liquid-crystalline properties of some novel alkyl furanosides

Monoalkyl substitution in carbohydrate systems is known to affect the melting behaviour of sugars and support the introduction of thermotropic liquid-crystalline phases. Similarly, the inclusion of a relatively long aliphatic chain in the molecular structure affects the formation of lyotropic liquid crystal phases. In some instances, long-chain-substituted carbohydrates can generate both lyotropic and thermotropic phases, and hence these materials have been described as amphitropic. Here, the thermotropic and lyotropic liquid-crystalline properties of an amphitropic family of monoalkylated furanosides are described. In addition, the thermal behaviour of the materials is discussed in terms of simple molecular models of geometrically optimised structures, and the resulting degree of hydrogen bonding possible for the various materials.

An efficient route to per-O-acetylated hexofuranoses

Anomeric mixtures of per-O-acetylated D-galacto-, D-gluco- and D-manno-furanose derivatives were prepared via the corresponding n-octyl hexofuranosides under mild acetolysis conditions. The crystal X-ray data of 1,2,3,5,6penta-O-acetyl-a-D-mannofuranose corroborate the proposed structures.