Trifluoroacetic acid-promoted ring contraction in 2,3-di-O-silylated O-galactopyranosides and hemiacetals

A pyranose ring contraction of 2,3-di-O-silylated O-galactopyranosides with retention of aglycone promoted by anhydrous trifluoroacetyc acid (TFA) in CH2Cl2 was demonstrated for the first time. In addition, TFA-promoted pyranose ring contraction of 2,3-bis-O-(triisopropylsilyl)-D-galactopyranose with formation of the corresponding anomeric triols in furanose form was successfully performed. A representative series of β-D-galactopyranosides with Me, Bn, allyl, or 3-(trifluoroacetamido)propyl aglycones has been investigated. TBDPS protective groups were found to be more stable than TIPS groups under conditions of TFA-promoted pyranose ring contraction. An easy access to 2,3-di-O-TBDPS substituted allyl and benzyl galactofuranosides and 2,3-bis-O-(triisopropylsilyl)-β-D-galactofuranose may present an advantage in synthesis of selectively protected monosacharide bilding blocks, useful for the synthesis of biologically important oligosaccharides.

DFT Based Comparative Studies of Some Glucofuranose and Glucopyranoside Esters and Ethers

Carbohydrate-based molecular scaffolding received significant interest due to its impact on the drug discovery and development in synthetic carbohydrate chemistry during the last couple of decades. In this respect, four glucose compounds in the furanose and pyranose forms with ester and ether functionality were selected for their structural, thermodynamic and chemical reactivity studies. PASS predication indicated that the glucose in the six-membered pyranose form was more prone to biological properties compared to their five-membered furanose form. Also, in the pyranose form acetate ester (3) had more potentiality than the ethyl ether (4). The HOMO-LUMO energy gaps were almost similar for both monosubstituted furanose and pyranose glucose indicating their almost similar reactivities. It was also inferred that these 6-O-substituted compounds followed Lipinski’s rule with the acceptable range of ADMET levels, and hence, safe from lethal proarrhythmic risks. Hopefully, these results can be used in the near future for their probable pharmaceutical use without any remarkable toxicity.

Rv1717 Is a Cell Wall - Associated β-Galactosidase of Mycobacterium tuberculosis That Is Involved in Biofilm Dispersion

Understanding the function of conserved hypothetical protein (CHP)s expressed by a pathogen in the infected host can lead to better understanding of its pathogenesis. The present work describes the functional characterization of a CHP, Rv1717 of Mycobacterium tuberculosis (Mtb). Rv1717 has been previously reported to be upregulated in TB patient lungs. Rv1717 belongs to the cupin superfamily of functionally diverse proteins, several of them being carbohydrate handling proteins. Bioinformatic analysis of the amino acid sequence revealed similarity to glycosyl hydrolases. Enzymatic studies with recombinant Rv1717 purified from Escherichia coli showed that the protein is a β-D-galactosidase specific for pyranose form rather than the furanose form. We expressed the protein in Mycobacterium smegmatis (Msm), which lacks its ortholog. In MsmRv1717, the protein was found to localize to the cell wall (CW) with a preference to the poles. MsmRv1717 showed significant changes in colony morphology and cell surface properties. Most striking observation was its unusual Congo red colony morphotype, reduced ability to form biofilms, pellicles and autoagglutinate. Exogenous Rv1717 not only prevented biofilm formation in Msm, but also degraded preformed biofilms, suggesting that its substrate likely exists in the exopolysaccharides of the biofilm matrix. Presence of galactose in the extracellular polymeric substance (EPS) has not been reported before and hence we used the galactose-specific Wisteria floribunda lectin (WFL) to test the same. The lectin extensively bound to Msm and Mtb EPS, but not the bacterium per se. Purified Rv1717 also hydrolyzed exopolysaccharides extracted from Msm biofilm. Eventually, to decipher its role in Mtb, we downregulated its expression and demonstrate that the strain is unable to disperse from in vitro biofilms, unlike the wild type. Biofilms exposed to carbon starvation showed a sudden upregulation of Rv1717 transcripts supporting the potential role of Rv1717 in Mtb dispersing from a deteriorating biofilm.

SYNTHESIS OF CARBOHYDRATE BLOCKS FOR 2'.3'-DIDEOXYNUCLEOSIDES FROM LEVOGLUCOSENONE

Nucleosides containing five-membered deoxy-carbohydrates in the glycosidic part, such as zalcitabine, 2'.3'-dideoxyuridine, stavudine, are widely used in acquired immunodeficiency syndrome (AIDS). A number of 2'.3'-dideoxynucleosides is an effective inhibitor of type-1 immunodeficiency virus (HIV-1) in humans. Levoglucosenone and cyrene (dihydrolevoglucosenone) are unique compounds, optically pure ketones of carbohydrate nature obtained from renewable bio-raw materials and available by pyrolysis of any cellulose-containing materials. They are promising carbohydrates for the production of modified nucleosides; in addition, they are commercially available. Based on levoglucosenone, we synthesized chiral carbohydrate blocks for dideoxy-nucleosides, namely, tertbutyldimethylsilyl derivatives of (S)-5-(hydroxymethyl)-2.5-dihydrofuran-2-ol and (S)-5-(hydroxymethyl)tetrahydrofuran-2-ol. At the first stage of the synthesis, a one-stage modification of the pyranose form of levoglucosenone and cyrene to γ-butanolides was carried out by Bayer-Williger oxidation using H2O2 in the presence of Amberlyst-15 in water. The reduction of unprotected hydroxymethyl-γ-butanolide obtained from cyrene to lactol was studied. The reduction of γ-butanolide by the action of BH3·SMe2, Red-Al, or LiAlH(OtBu)3 in THF at 0° C leads mainly to triol, the product of complete reduction. The desired lactol was obtained using iBu2AlH at -78°C in CH2Cl2 in good yield. Raising the reaction temperature to 0° C led to a decrease in the yield of lactol. It has been established that (S)-5-(hydroxymethyl)-tetrahydrofuran-2-ol exists in both five-membered and six-membered forms. Due to the fact that the target lactols easily undergo a transition from the furanose to the pyranose form, they are not used to produce nucleosides. Therefore, we have studied the approach to the synthesis of stable five- membered lactols. For this purpose, in lactones obtained by the Bayer-Williger reaction, the primary hydroxyl group was blocked using TBSCl. Subsequent reduction of the esters using iBu2AlH gave lactols that existed exclusively in the furanose form. The total yield of the target (S)-5-(hydroxymethyl)-2.5-dihydrofuran-2-ol obtained from levoglucosenone was 39% and (S)-5-(hydroxymethyl)-tetrahydrofuran-2-ol obtained from cyrene was 65%.

Spectroscopic diagnostic for the ring-size of carbohydrates in the gas phase: furanose and pyranose forms of GalNAc

Hexoses are sparingly found in nature in the furanose form (5-membered ring).

Binding interaction between 2-methoxy-5-fluoro phenyl boronic acid and sugars: Effect of structural change of sugars on binding affinity

The binding interaction of 2-methoxy-5-fluoro phenyl boronic acid with various sugars like dextrose, arabinose, xylose, sucrose, and lactose is investigated in aqueous medium at pH 7.4 using the fluorescence spectroscopic method. Fluorescence intensity is reduced upon addition of sugars. The change in the intensity is attributed to breaking of intramolecular hydrogen bonding and to the lesser stability of boronic ester. Data are analyzed using the Benesi–Hildebrand equation and Lineweaver–Burk equation. The estimated binding constants are greater in mono sugars arabinose and xylose. The fact that a structural change in sugar arises due to mutarotation plays a major role in binding interactions. The furanose form of the sugar is found to be more favoured for binding.

Synthesis and anti-mycobacterial activity of glycosyl sulfamides of arabinofuranose

A series ofarabino N-glycosyl sulfamides, forced to adopt the furanose form by removal of the 5-hydroxyl group, were synthesised as putative isosteric mimics of decaprenolphosphoarabinose, the donor processed by arabinosyltransferases during mycobacterial cell wall assembly.

The Study of the Reaction of Pectin-Ag(0) Nanocomposites Formation

Pectin polysaccharides (PSs) were isolated from a bark of Larix sibirica Ledeb. Structure of PS fragments determined by chemical transformations, chromatography, and spectroscopic analyses was found to be a linear galacturonane comprising 1,4-linked α-D-GalpA residues and a rhamnogalacturonan I (RG-I). The fifth part of galacturonane residues was methyl esterified at at C-2 and/or C-3 and C-6 atoms. Some of RG-I side chains were identified as arabinogalactan subunits with highly branched structure consisting of linear backbone with3,6)-β-D-Galp-(1residues, substituted at C-6 by neutral side chains. This side chains contained2,5)-α-L-Araf-(1and3,5)-α-L-Araf-(1residues and terminal arabinose in the pyranose and furanose form. It was found that “pectin-Ag(0)” nanobiocomposites were formed via the interaction between PS aqueous solutions and silver nitrate, with PS playing both reducing and stabilizing functions. It was shown that the content of Ag(0) particles in “pectin-Ag(0)” depended on the reaction conditions and can range from 0.1 to 72 %, the size of Ag(0) particles being 3–27 nm. Using 13C NMR technique, it was revealed that PS underwent destructive changes and they they were more considerable, more than the lot of Ag(I) that was inputed into the reactionary medium.

Synthese furanoider Zuckeraminos¨auren ausgehend von fermentativ gewonnener 2-Oxo-D-gluconsäure / Synthesis of Furanoid Sugar Amino Acids Starting from Fermentatively Produced 2-Oxo-D-gluconic Acid

2-Oxo-D-gluconic acid obtained by fermentation of D-glucose was used as starting material for syntheses of amino acids. We trapped the carbohydrate in its furanoid configuration and synthesized an α- and an ω-amino acid. After deprotection of the hydroxyl groups the latter did not isomerize to the substituted piperidine (aza-sugar) as expected, but remained in the furanose form. The starting structure 2 was proven by crystal structure analysis. The conformational identification of the other substances was done by NMR measurements following known rules for furanoses.