Synthetic Carbohydrate Chemistry Research Articles

The 2nd National Conference on Synthetic Carbohydrate Chemistry, Chinese Chemical Society (CARB 2017, CCS)

The 2nd National Conference on Synthetic Carbohydrate Chemistry, Chinese Chemical Society (CARB 2017, CCS)

ChemInform Abstract: Efficient and Selective N‐, S‐ and O‐Acetylation in TEAA Ionic Liquid as Green Solvent. Applications in Synthetic Carbohydrate Chemistry.

ChemInform Abstract: Efficient and Selective N‐, S‐ and O‐Acetylation in TEAA Ionic Liquid as Green Solvent. Applications in Synthetic Carbohydrate Chemistry.

Efficient and Selective N-, S- and O-Acetylation in TEAA Ionic Liquid as Green Solvent. Applications in Synthetic Carbohydrate Chemistry

Background: The ionic liquid triethylammonium acetate (TEAA) was found to be an efficient solvent in the acetylation of alcohols, amines, oximes and thiols to their corresponding acetyl compounds using only a 10% excess of acetic anhydride under mild conditions. Moreover TEAA is not only an inexpensive and recyclable solvent but also an anomeric selective catalyst in the per-Oacetylation of sugar moieties. Methods: Simple and effective organic synthesis protocols were provided for the selective acetylation of several substrates. The products were fully characterized by 1H and 13C NMR spectroscopy and the anomeric ratios were obtained from the 1H spectra. Results: Structurally diverse alcohols, phenols, thiols, amines, carbohydrates and oximes underwent acylation under mild conditions by this procedure to provide the corresponding acetates in excellent yields. TEAA ionic liquid is unique in its capability to act as both, solvent and high selective catalyst. As expected, the reaction proceeds with high b anomeric selectivity for sugars derivatives. Moreover, the ionic liquid was regenerated, recycled and reused for three times without apparent loss of reactivity and selectivity in all cases. Conclusions: The present procedure provides a powerful and versatile acylation method for alcohols, phenols, thiols, amines, oximes and carbohydrates. This protocol is endowed with several unique merits: selectivity, cost-efficiency, atom-economy and mild reaction conditions tolerable to acid sensitive functionalities. With these features, this method may be considered as a better alternative for the acetylation of a wide range of substrates. Keywords: Acylation, carbohydrates, green chemistry, triethylammonium acetate (TEAA).

Geert-Jan Boons

Citation: For seminal contributions to glycoscience by developing novel methods for oligosaccharide assembly, preparation of important glycoconjugates, and their use in biological studies. Current position: UGA Foundation Distinguished Professor in Biomedical Sciences, University of Georgia; professor and chair, department of medicinal chemistry and chemical biology, Utrecht University Education: B.S. and M.Sc., chemistry, Ph.D., synthetic carbohydrate chemistry, Leiden University Boons on his biggest research challenge: “Design, synthesis, and immunological evaluation of a multicomponent vaccine that could break immunotolerance to a tumor-associated glycopeptide epitope and elicit innate, cellular, and humoral immune responses. The ultimate aim of this program is to develop a therapeutic vaccine for cancer based on a type of glycosylation uniquely found on cancer cells.” What his colleagues say: “Dr. Boons’s prolific contributions to glycoscience have earned him a highly respected international reputatio...

Chiral Catalyst-Directed Dynamic Kinetic Diastereoselective Acylation of Lactols for De Novo Synthesis of Carbohydrate.

The control of the stereochemistry at the anomeric position is still one of the major challenges of synthetic carbohydrate chemistry. We have developed a new strategy consisting of a chiral catalyst-directed acylation followed by a palladium-catalyzed glycosidation to achieve high α- and β-stereoselectivity on the anomeric position. The former process involves a dynamic kinetic diastereoselective acylation of lactols derived from Achmatowicz rearrangement, while the latter is a stereospecific palladium-catalyzed allylic alkylation.

ChemInform Abstract: Stereocontrolled 1,2‐cis Glycosylation as the Driving Force of Progress in Synthetic Carbohydrate Chemistry

AbstractReview: [137 refs.

The targeted recognition of Lactococcus lactis phages to their polysaccharide receptors.

Each phage infects a limited number of bacterial strains through highly specific interactions of the receptor-binding protein (RBP) at the tip of phage tail and the receptor at the bacterial surface. Lactococcus lactis is covered with a thin polysaccharide pellicle (hexasaccharide repeating units), which is used by a subgroup of phages as a receptor. Using L. lactis and phage 1358 as a model, we investigated the interaction between the phage RBP and the pellicle hexasaccharide of the host strain. A core trisaccharide (TriS), derived from the pellicle hexasaccharide repeating unit, was chemically synthesised, and the crystal structure of the RBP/TriS complex was determined. This provided unprecedented structural details of RBP/receptor site-specific binding. The complete hexasaccharide repeating unit was modelled and found to aptly fit the extended binding site. The specificity observed in in vivo phage adhesion assays could be interpreted in view of the reported structure. Therefore, by combining synthetic carbohydrate chemistry, X-ray crystallography and phage plaquing assays, we suggest that phage adsorption results from distinct recognition of the RBP towards the core TriS or the remaining residues of the hexasacchride receptor. This study provides a novel insight into the adsorption process of phages targeting saccharides as their receptors.

A recyclable heavy fluorous tag carrying an allyl alcohol pendant group: design and evaluation toward applications in synthetic carbohydrate chemistry

Toward applications in synthetic carbohydrate chemistry, we converted our previous acid-resistant heavy fluorous tag [(Rf)3C–CH2–OH, 1] to allyl alcohol derivatives [(Rf)3C–CH2–O–(CH2)n–CHCH–CH2–OH, 3 (n=1) or 4 (n=3)] by means of olefin cross metathesis. They were then subjected to β-glycosylation reactions by using a series of glycosyl donors, including glycosyl bromide and trichloroacetimidates. The terminal OH group in 3 and 4 was found to be β-glycosylated in moderate yield when 2,3,4,6-tetra-O-benzoyl-d-galactosyl trichloroacetimidate was used as the glycosyl donor. Upon a detachment reaction using Pd(PPh3)4, the initial heavy fluorous tag 1 was recovered in high yield (>90%) together with 1-hydroxy sugar, indicating that not only the allyl ether linkage in the glycosides but also the internal di-alkyl ether linkage in 4 be cleaved by the action of the Pd-catalyst enabling long-range olefin transmigration. Potential utility was demonstrated by using the tetra-O-benzoyl-β-d-galactosylated derivative of 3 in a series of deprotection, protection and glycosylation reactions, which were conductible in high yields without using chromatographic purification process. These findings prompt us to propose a general scheme in which the acid-resistant heavy fluorous compound 1 is applied as a recyclable tag in synthetic carbohydrate chemistry.

Stereocontrolled 1,2-cis glycosylation as the driving force of progress in synthetic carbohydrate chemistry.

Recent developments in stereoselective 1,2-cisglycosylation that have emerged during the past decade are surveyed herein.

ChemInform Abstract: In situ Preactivation Strategies for the Expeditious Synthesis of Oligosaccharides: A Review

AbstractReview: 74 refs.

Experimental and computational studies of nJ(77Se,1H) selenium–proton couplings in selenoglycosides

Selenoglycosides are important starting materials in synthetic carbohydrate chemistry and play a role in biological interactions as well. Both aspects are influenced by the conformation around the glycosidic bond. Here, we present a combined experimental and computational approach to measure and evaluate (n)J((77)Se, (1)H) coupling constants for their use in conformational analysis. The measurements were carried out using a modified CPMG-HSQMBC pulse scheme which yields pure absorption antiphase multiplets to allow accurate determination of the (n)J(XH) values regardless of the size of the proton-proton couplings. Theoretical calculations were performed at the Second-Order Polarization Propagator Approach (SOPPA) level. Population-averaged values calculated for geminal and vicinal couplings are in a good agreement with experiment indicating an adequate theoretical level of the calculations. Experimental observations and computations alike have indicated that two-bond (77)Se-(1)H couplings, (2)J((77)Se, (1)H), in a H1-C1-Se-X moiety are very sensitive to the torsion angle around the C1-Se-bond and will, therefore, be useful for conformational studies.

Characterisation of recombinant pyranose oxidase from the cultivated mycorrhizal basidiomycete Lyophyllum shimeji (hon-shimeji).

BackgroundThe flavin-dependent enzyme pyranose 2-oxidase (P2Ox) has gained increased attention during the last years because of a number of attractive applications for this enzyme. P2Ox is a unique biocatalyst with high potential for biotransformations of carbohydrates and in synthetic carbohydrate chemistry. Recently, it was shown that P2Ox is useful as bioelement in biofuel cells, replacing glucose oxidase (GOx), which traditionally is used in these applications. P2Ox offers several advantages over GOx for this application, e.g., its much broader substrate specificity. Because of this renewed interest in P2Ox, knowledge on novel pyranose oxidases isolated from organisms other than white-rot fungi, which represent the traditional source of this enzyme, is of importance, as these novel enzymes might differ in their biochemical and physical properties.ResultsWe isolated and over-expressed the p2ox gene encoding P2Ox from the ectomycorrhizal fungus Lyophyllum shimeji. The p2ox cDNA was inserted into the bacterial expression vector pET21a(+) and successfully expressed in E. coli Rosetta 2. We obtained active, flavinylated recombinant P2Ox in yields of approximately 130 mg per L of medium. The enzyme was purified by a two-step procedure based on anion exchange chromatography and preparative native PAGE, yielding an apparently homogenous enzyme preparation with a specific activity of 1.92 U/mg (using glucose and air oxygen as the substrates). Recombinant P2Ox from L. shimeji was characterized in some detail with respect to its physical and catalytic properties, and compared to the well-characterised enzymes from Phanerochaete chrysosporium and Trametes multicolor.ConclusionL. shimeji P2Ox shows properties that are comparable to those of P2Ox from white-rot fungal origin, and is in general characterised by lower Km and kcat values both for electron donor (sugar) as well as electron acceptor (ferrocenium ion, 1,4-benzoquinone, 2,6-dichloroindophenol). While L. shimeji P2Ox is the least thermostable of these three enzymes (melting temperature Tm of 54.9°C; half-life time of activity τ1/2 of 0.12 at 50°C and pH 6.5), P. chrysosporium P2Ox showed remarkable thermostability with Tm of 75.4°C and τ1/2 of 96 h under identical conditions.

S- and C-nucleosidoquinazoline as new nucleoside analogs with potential analgesic and anti-inflammatory activity

Thioglycosides and C-glycosides have received considerable attention, because they are widely employed as biological inhibitors, inducers and ligands for affinity chromatography of carbohydrate-processing enzymes and proteins. Moreover, they are promising candidates in synthetic carbohydrate chemistry as convenient and versatile glycosyl donors. Among these glycosyl donors are the thioglycosyl and N-glycosyl heterocycles that are sufficiently stable under a variety of reaction conditions and have the ability to be readily converted into a variety of other functionalities. We report here, the synthesis of 2-thioxo-quinazolines 1a– c which were used as a base to the synthesis of S-nucleoside of types 10, 11 and acyclic C-nucleoside analogs of type 14 and their analgesic and anti-inflammatory activities were evaluated giving good results.

Indium(III) Triflate: A Highly Efficient Catalyst for Reactions of Sugars[1

Indium(III) trifluoromethanesulfonate has been found to be extremely efficient in catalyzing acyl transfer reactions of various carbohydrates and their derivatives. Selective acetolyses of certain benzyl ethers/isopropylidene acetals of sugars have been possible using In(OTf)3 in Ac2O (neat). Reaction of the per-O-acetate of 2-deoxy-2-phthalimido-D-glucose with benzyl mercaptan in the presence of In(OTf)3 led to the formation of the corresponding thioglycoside in high yield. Facile formation and hydrolysis of the isopropylidene and benzylidene acetals of various carbohydrates have also been achieved very efficiently in the presence of In(OTf)3. The results show great promise for In(OTf)3 in synthetic carbohydrate chemistry.

Recent Advances in Carbohydrate Microarrays

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Carbohydrate Microarrays as Tools in HIV Glycobiology

Progress in carbohydrate microarray technology has positioned the glycochip among the expanding set of biophysical tools available to researchers. Synthetically-derived glycochips unite established microarray techniques with the versatility and structural precision of synthetic carbohydrate chemistry. A comprehensive demonstration of carbohydrate microarrays is illustrated by the chip-based study of protein/carbohydrate and protein/glycoprotein interactions as they relate to HIV glycobiology. Composed of a series of high-mannose oligosaccharides, carbohydrate microarrays were prepared utilizing a covalent linking strategy to immobilize synthetically-defined glycans in a uniform orientation. In concert with a simple glycoprotein array, these microarrays were used to establish the individual and competitive binding profiles of five gp120 binding proteins--DC-SIGN, CD4, 2G12 cyanovirin-N, and scytovirin--and established the carbohydrate structural requirements for these interactions.

Syntheses of Peptidomimetics Based on Pyranose and Polyhydroxylated Piperidine Scaffolds

There has been significant progress in application of pyranoses and related compounds towards drug discovery and development. This review focuses on strategies for grafting of pharmacophore groups at selected positions on pyranoside and related iminosugar scaffolds. Recent developments in the solid phase synthesis of prospecting combinatorial libraries, syntheses of pyranose based sugar amino acids (SAAs) and other scaffolding for peptidomimetics are included. Although no drug molecule has been developed a number of novel potent ligands for receptors have been identified. It has been shown that these pyranoside derivatives could have improved cellular permeability over peptides. Progress in this area is continually dependant on advances in synthetic carbohydrate chemistry both in solution and on solid phase. These include the development of orthogonal protecting group strategies, strategies for regioselective manipulation of pyranoside hydroxyl groups and strategies that could take increasing advantage of chemoselective reactions. In addition a greater understanding of structural carbohydrate chemistry and the preferred orientations of groups attached to pyranose scaffolds may facilitate synthesis of more potent ligands for receptors. Keywords: nojirimycin, Somatostatin antagonist, D-allopyranose, carbohydrate-based peptidomimetics, Lipidic peptidomimetics, fibrinogen receptor antagonist

Recent Advances in Carbohydrate Microarrays

AbstractCarbohydrate microarrays have become a powerful tool to elucidate the biological role of these important biomolecules. This minireview focuses on the most recent advances involving carbohydrate microarrays, including the use of sugar arrays to study carbohydrate–cell interactions and to detect pathogens. Other important developments are novel immobilization strategies to covalently attach unmodified carbohydrates and the application of this robotic technology to the printing of medium‐size (more than 200 compounds) glycan libraries using reproducible amide bond formation and standard DNA array protocols. Recent advances in synthetic carbohydrate chemistry, such as the development of the automated solid‐phase oligosaccharide synthesizer, will increase the complexity and utility of carbohydrate microarrays. Carbohydrate arrays are beginning to have a major impact in the field of glycomics, aiding the discovery of new roles for carbohydrates in cell biology.

Acetal Protecting Groups in the Organic Laboratory: Synthesis of Methyl 4,6-O-Benzylidene-α-D-Glucopyranoside

A laboratory procedure for the synthesis of methyl 4,6-O-benzylidene-α-D-glucopyranoside is described. This compound is obtained in one synthetic step from commercially available methyl α-D-glucopyranoside. Purification of the target compound is achieved by precipitation from organic solvents. The experiment has given our undergraduate students an exposure to practical synthetic carbohydrate chemistry. In addition, the experiment provides an opportunity to synthesize a cyclic acetal; stereoselectively introduce a chirality center; learn extraction, evaporation, precipitation, optical rotation, melting point measurement, thin-layer chromatography, IR-spectroscopy, mass spectrometry, and various NMR techniques. The extended experiment for the advanced organic laboratory as a part of a multistep synthesis or identification of unknowns has been also developed.

Synthesis, Glycosidation, and Hydrolytic Stability of Novel Glycosyl Thioimidates.

AbstractFor Abstract see ChemInform Abstract in Full Text.