Environmentally benign glycosylation of aryl pyranosides and aryl/alkyl furanosides demonstrating the versatility of thermostable CGTase from Thermoanaerobacterium sp.

International audienceAn extensive study on the specificity of transglycosylation and disproportionation of Thermoanaerobacterium sp. cyclodextrin glucosyltranferases against aryl glucopyranosides or furanosides was achieved. While a mixture of maltoside and isomaltoside was obtained respectively using p-nitrophenyl glucopyranoside as acceptor, only one regioisomer, namely the p-nitrophenyl α-D-Glcp-(1,3)-α-L-Araf was isolated using p-nitrophenyl arabinofuranoside as acceptor. Interestingly, similar outcomes were found when using p-nitrophenyl galactofuranoside. Furthermore, activation by microwave irradiation resulted in faster reaction times and higher yields and led to glucosidic oligosaccharides with up to 70% conversion. The influence of the anomeric and C-4 configurations of the glycosidic acceptors on the transglycosylation, previously stated for the CGTase family, was not observed and unconventional substrate specificity towards alkyl furanosides was highlighted

Exploring the synthetic potency of the first furanothioglycoligase through original remote activation.

International audienceThioglycosidic bonds are of utmost importance in biomolecules as their incorporation led to more stable glycomimetics with potential drug activities. Until now only chemical methods were available for their incorporation into glycofuranosyl conjugates. Herein, we wish to describe the use of the first furanothioglycoligase for the preparation of a great variety of thioaryl derivatives with moderate to excellent yields. Of great interest, a stable 1-thioimidoyl arabinofuranose, classically used in chemical glycosylation, was able to efficiently act as a donor through an original enzymatic remote activation mechanism. Study of the chemical structure as well as the nucleophilicity of the thiol allowed us to optimize this biocatalyzed process. As a consequence, this mutated enzyme constitutes an original, mild and eco-friendly method of thioligation

Molecular Interactions of β-(1→3)-Glucans with Their Receptors

β-(1→3)-Glucans can be found as structural polysaccharides in cereals, in algae or as exo-polysaccharides secreted on the surfaces of mushrooms or fungi. Research has now established that β-(1→3)-glucans can trigger different immune responses and act as efficient immunostimulating agents. They constitute prevalent sources of carbons for microorganisms after subsequent recognition by digesting enzymes. Nevertheless, mechanisms associated with both roles are not yet clearly understood. This review focuses on the variety of elucidated molecular interactions that involve these natural or synthetic polysaccharides and their receptors, i.e., Dectin-1, CR3, glycolipids, langerin and carbohydrate-binding modules

Etude d'aza-analogues des alcaloïdes marins de type pyrroloquinoline, wakayine et tsitsikammamines à activité antitumoral potentielle (approche vers la synthèse totale des produits naturels)

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

Regioselective glycosylation: What's new?

International audienceThe aim of this chapter is to show how increased understanding of the mechanisms related to both carbohydrate-processing enzymes and intrinsic properties of monoglycosyl residue have significantly impacted our way of thinking about the glycosylation reaction. A focus is made on the importance of low energy interactions. Some recent examples related to biocatalytic approaches and chemical synthesis are given

Two-step synthesis of per-O-acetylfuranoses: optimization and rationalization.

International audienceA simple two-step procedure yielding peracetylated furanoses directly from free aldoses was implemented. Key steps of the method are (i) highly selective formation of per-O-(tert-butyldimethylsilyl)furanoses and (ii) their clean conversion into acetyl ones without isomerization. This approach was easily applied to galactose and structurally related carbohydrates such as arabinose, fucose, methyl galacturonate and N-acetylgalactosamine to give the corresponding peracetylated targets. The success of this procedure relied on the control of at least three parameters: (i) the tautomeric equilibrium of the starting unprotected oses, (ii) the steric hindrance of both targeted furanoses and silylating agent, and finally, (iii) the reactivity of each soft nucleophile during the protecting group interconversion

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

International audienceTerpene compounds probably represent the most diversified class of secondary metabolites. Some classes of terpenes, mainly diter-penes (C20) and sesterterpenes (C25) and to a lesser extent sesquiterpenes (C15), share a common bicyclo[3.6.0]undecane core which is characterized by the presence of a cyclooctane ring fused to a cyclopentane ring, i.e., a [5-8] bicyclic ring system. This review focuses on the different strategies elaborated to construct this [5-8] bicyclic ring system and their application in the total synthesis of terpenes over the last two decades. The overall approaches involve the construction of the 8-membered ring from an appropriate cyclopentane precursor. The proposed strategies include metathesis, Nozaki-Hiyama-Kishi (NHK) cyclization, Pd-mediated cyclization, radical cyclization, Pauson-Khand reaction, Lewis acid-promoted cyclization, rearrangement, cycloaddi-tion and biocatalysis

How recent knowledge on furano-specific enzymes has renewed interest for the synthesis of glycofuranosyl-containing conjugates

International audienced-Galactose in its furanose form is undoubtedly an enigma in glycosciences that has triggered numerous chemical, physical and biological studies over the last thirty years. This chapter is dedicated to show how chemists have been inspired by enzymes involved in the biosynthesis and metabolism of furanosyl-containing conjugates. The resulting molecular tools have proven to be essential for better understanding mutases, furanosyl transferases and furanosyl hydrolases, their impact, their activity and the corresponding biochemical pathways. Moreover, this chapter includes some examples highlighting the use of modern NMR techniques and of molecular biology as new tools in chemical laboratories that contributed to the elucidation of mechanism pathways and/or to the production of new biocatalysts useful for the synthesis of furanosyl-containing conjugates

Diversion of a thioglycoligase for the synthesis of 1-O-acyl arabinofuranoses

International audienceAn arabinofuranosylhydrolase from the GH51 family was transformed into an acyl transferase by mutation of the catalytic acid/base amino acid. The resulting enzyme was able to transfer carboxylic acid onto the anomeric position of arabinose with complete chemo- and stereoselectivity. A wide range of acyl α-l-arabinofuranoses was obtained with yields ranging from 25 to 83%. Using this method, ibuprofen and N-Boc phenylalanine were successfully transformed into their corresponding acyl conjugates, expanding the scope of the reaction to drugs and amino acids

Improvement of the versatility of an arabinofuranosidase against galactofuranose for the synthesis of galactofuranoconjugates

International audienceGalactofuranoconjugates are rare compounds with interesting biological properties. Their syntheses by traditional approaches are however tedious. Glycosidases are nowadays often used to simplify such syntheses but the use of galactofuranosidase has not been described yet for the synthesis of galactofuranoconjugates. Interestingly CtAraf51, an α-l-arabinofuranosidase from Ruminiclostridium thermocellum, is able to use aryl- or alkyl-β-d-galactofuranosides as the substrate but with very low efficiency. To allow its use as a synthesis tool, we decided to improve the efficiency of this enzyme toward these non-natural substrates. First, we identified three residues that can contribute to unfavorable interactions with the p-nitrophenyl-β-d-galactofuranoside. After mutagenesis, two mutants have shown a catalytic efficiency four- and threefold higher than that of the wild type, respectively. These two mutants were then evaluated in the transglycosylation reaction using ethanol as a model acceptor substrate. Under these conditions one mutant was much more efficient 50% conversion was reached ten times faster than with the WT. Finally both mutants were converted into thioglycoligases in the thioligation reaction, the reaction was two times faster than with the E173A single mutant, and in the acylation reaction a fourfold increase in the initial velocity was found. The synthetic potential of the resulting mutants to synthesize various O-, S- and acyl galactofuranoconjugates was further evaluated and yields up to 82% were obtained for the synthesis of ethyl- or thiophenyl galactofuranosides and methoxybenzoic galactofuranose