Total Synthesis of Tri-, Hexa- and Heptasaccharidic Substructures of the O-Polysaccharide of Providencia rustigianii O34

A general and efficient strategy for synthesis of tri-, hexa- and heptasaccharidic substructures of the lipopolysaccharide of Providencia rustigianii O34 is described. For the heptasaccharide seven different building blocks were employed. Special features of the structures are an α-linked galactosamine and the two embedded α-fucose units, which are either branched at positions-3 and -4 or further linked at their 2-position. Convergent strategies focused on [4+3], [3+4], and [4+2+1] couplings. Whereas the [4+3] and [3+4] coupling strategies failed the [4+2+1] strategy was successful. As monosaccharidic building blocks trichloroacetimidates and phosphates were employed. Global deprotection of the fully protected structures was achieved by Birch reaction.     

Biomolecular Densely Grafted Brush Polymers: Oligonucleotides,Oligosaccharides and Oligopeptides

In this Minireview, we describe synthetic polymers densely functionalized with sequence-defined biomolecular sidechains. We focus on synthetic brush polymers of oligonucleotides, oligosaccharides, and oligopeptides, prepared via graft-through polymerization from biomolecule functionalized monomers. The resulting structures are brush polymers wherein a biomolecular graft is positioned at each monomer backbone unit. We describe key synthetic milestones, identify synthetic opportunities, and highlight recent advances in the field, including biological applications.     

Synthesis of quercetin 3-O-β-d-apiofuranosyl-(1→2)-[α-l-rhamnopyranosyl-(1→6)]-β-d-glucopyranoside

A concise method to construct a unique 2,6-branched trisaccharide was established by regioselective glycosylation of three free hydroxyl groups on a 3-O-protected glucose moiety, and successfully used in the synthesis of quercetin 3-O-β-d-apiofuranosyl-(1→2)-[α-l-rhamnopyranosyl-(1→6)]-β-d-glucopyranoside, a flavonol O-glycoside isolated from glandless cotton seeds which showed notable antidepressant activities.     

Divergent heparin oligosaccharide synthesis with preinstalled sulfate esters

Traditional chemical synthesis of heparin oligosaccharides first involves assembly of the full length oligosaccharide backbone followed by sulfation. Herein, we report an alternative strategy in which the O-sulfate was introduced onto glycosyl building blocks as a trichloroethyl ester prior to assembly of the full length oligosaccharide. This allowed divergent preparation of both sulfated and non-sulfated building blocks from common advanced intermediates. The O-sulfate esters were found to be stable during glycosylation as well as typical synthetic manipulations encountered during heparin oligosaccharide synthesis. Furthermore, the presence of sulfate esters in both glycosyl donors and acceptors did not adversely affect the glycosylation yields, which enabled us to assemble multiple heparin oligosaccharides with preinstalled 6-O-sulfates.     

Neighboring-group participation by C-2 ether functions in glycosylations directed by nitrile solvents

Ether-protecting functions at C-2 hydroxy groups have been found to play participating roles in glycosylations when the reactions are conducted in nitrile solvent mixtures. The participation mechanism is based on intramolecular interaction between the lone electron pair of the oxygen atom of the C-2 ether function and the nitrile molecule when they are positioned in a cis configuration. A 1,2-cis glycosyl oxazolinium intermediate is formed. This participation, in conjunction with the anomeric effect of the glycosyl donor, confers high 1,2-trans selectivities on glycosylations. Further application of this concept has led to efficient preparations of α-(1→5)-arabinan oligomers.     

Degradation of Target Oligosaccharides by Anthraquinone–Lectin Hybrids with Light Switching

Anthraquinone–lectin hybrids were effectively synthesized using water‐soluble anthraquinone derivative 11 with concanavalin A (ConA) and hygrophorus russula lectin (HRL) to give anthraquinone–ConA ( 16 ) and anthraquinone–HRL ( 17 ) hybrids, respectively. These anthraquinone–lectin hybrids effectively and selectively degraded oligosaccharides containing a mannose residue as a non‐reducing terminal sugar, which has affinity for ConA and HRL, under photo‐irradiation with long‐wavelength UV light without additives and under neutral conditions. In addition, anthraquinone–HRL ( 17 ) selectively photo‐degraded only Man(α1,6)Man, which has a high affinity for HRL, among several mannosides by recognition of both the type and glycosidic linkage profile of the sugar in an oligosaccharide.     

Gold Manno‐Glyconanoparticles: Multivalent Systems to Block HIV‐1 gp120 Binding to the Lectin DC‐SIGN

The HIV envelope glycoprotein gp120 takes advantage of the high‐mannose clusters on its surface to target the C‐type lectin dendritic cell‐specific intracellular adhesion molecule‐3‐grabbing non‐integrin (DC‐SIGN) on dendritic cells. Mimicking the cluster presentation of oligomannosides on the virus surface is a strategy for designing carbohydrate‐based antiviral agents. Bio‐inspired by the cluster presentation of gp120, we have designed and prepared a small library of multivalent water‐soluble gold glyconanoparticles (manno‐GNPs) presenting truncated (oligo)mannosides of the high‐mannose undecasaccharide Man₉GlcNAc₂ and have tested them as inhibitors of DC‐SIGN binding to gp120. These glyconanoparticles are ligands for DC‐SIGN, which also interacts in the early steps of infection with a large number of pathogens through specific recognition of associated glycans. (Oligo)mannosides endowed with different spacers ending in thiol groups, which enable attachment of the glycoconjugates to the gold surface, have been prepared. manno‐GNPs with different spacers and variable density of mannose (oligo)saccharides have been obtained and characterized. Surface plasmon resonance (SPR) experiments with selected manno‐GNPs have been performed to study their inhibition potency towards DC‐SIGN binding to gp120. The tested manno‐GNPs completely inhibit the binding from the micro‐ to the nanomolar range, while the corresponding monovalent mannosides require millimolar concentrations. manno‐GNPs containing the disaccharide Manα1‐2Manα are the best inhibitors, showing more than 20 000‐fold increased activity (100 % inhibition at 115 nM ) compared to the corresponding monomeric disaccharide (100 % inhibition at 2.2 mM ). Furthermore, increasing the density of dimannoside on the gold platform from 50 to 100 % does not improve the level of inhibition.     

Electrospray multistage mass spectrometry in the negative ion mode for the unambiguous molecular and structural characterization of acidic hydrolysates from 4‐O‐methylglucuronoxylan generated by endoxylanases

A rapid analytical methodology is proposed to answer the two questions about the molecular and structural features of the acidic xylo‐oligosaccharides (XOSs) formed upon the enzymatic hydrolysis of 4‐O‐methylglucuronoxylan. The shortest acidic XOSs carrying a methylglucuronic acid moiety and the possible distribution of larger products (molecular feature) are instantly found by electrospray ionization mass spectrometry (ESI‐MS) in the negative ion mode, which filters the unwanted neutral XOS. The acidic moiety is then unambiguously localized along the xylose backbone (structural feature) by ESI‐MSⁿ in the negative ion mode via the selection/activation/dissociation of the product ions formed upon the one‐way and stepwise glycosidic bond cleavage at the reducing end. Using the shortest acidic XOS with a known shape generated by glycoside hydrolase family (GH) 10 and GH11 xylanases as a proof of principle, pairs of diagnostic ions are proposed to instantly interpret the MSⁿ fingerprints and localize the acidic moiety along the xylose chain of the activated ion. The original structure of the acidic XOS is then reconstructed by adding as many xylose units at the reducing end as MSⁿ steps. Relying on pairs of ions, the methodology is robust enough to highlight the presence of isomeric products. Mass spectra reported in the present article will be conveniently used as reference data for the forthcoming analysis of acidic XOS generated by new classes of enzymes using this multistage mass spectrometry methodology.     

Electrochemical Glycosylation as an Enabling Tool for the Stereoselective Synthesis of Cyclic Oligosaccharides

Electrochemical glycosylation of a linear oligosaccharide with a protecting-group-free primary hydroxyl group afforded cyclic oligo-saccharides, up to hexasaccharides, in high yields. Precursors of the cyclic oligosaccharides were prepared by automated electro-chemical assembly-a method for the automated electrochemical solution-phase synthesis of oligosaccharides. We demonstrated that electrochemical glycosylation is useful not only for intermolecular glycosylation but also for intramolecular glycosylation to synthesize cyclic oligosaccharides.