First synthesis of 3′-deoxy Lewisx pentasaccharide

The total synthesis of 3′-deoxy Lewis^x pentasaccharide is reported. 4-O-Acetyl-2,6-di-O-benzoyl-3-deoxy-β-d-xylo-hexopyranosyl trichloroacetimidate was condensed with a diol of glucosamine to give a disaccharide, which was further fucosylated to a Lewis^x trisaccharide analogue. Glycosylation of a lactoside diol with this trisaccharide provided a pentasaccharide, which after deprotection, afforded the target pentasaccharide.     

Synthesis of 3″- and 4″-deoxy-Lewisx trisaccharides: A useful tool for study of carbohydrate-carbohydrate interaction

Synthesis of 3″-deoxy and 4″-deoxy Lewis^x trisaccharides is described. Phenyl 2,3,6-tri-O-benzoyl-4-deoxy-1-thio-β-d-xylo-hexopyranoside was condensed with a diol of glucosamine to give regio- and stereo-selectively a disaccharide. Stereoselective fucosylation of this disaccharide provided a protected deoxy Lewis^x trisaccharide which was deprotected to give the 4″-deoxy Lewis^x trisaccharide. Application of the similar synthetic sequence provided the 3″-deoxy Lewis^x trisaccharide.     

Lewisx五糖的有效合成: 发展DC-靶向疫苗的有效分子

将选择性保护的乳糖二醇与Lewis^x三糖在N-碘代丁二酰亚胺(NIS)/TfOH催化下高立体、高区域选择性糖苷化得Lewis^x五糖, 后者脱保护后获得目标五糖, 总收率67.7%. 化合物结构经NMR, MS和元素分析确证.     

Glycoproteomic characterization of carriers of the CD15/Lewis<Superscript>x</Superscript> epitope on Hodgkin's Reed-Sternberg cells

Background  

The Lewis^x trisaccharide, also referred to as the CD15 antigen, is a diagnostic marker used to distinguish Hodgkin's lymphoma from other lymphocytic cancers. However, the role of such fucosylated structures remains poorly understood, in part because carriers of Lewis^x structures on Hodgkin's Reed-Sternberg cells have not been identified.     

An Efficient Synthesis of Sulfo Lewis X Analog Containing 1-Deoxynojirimycin 1

Abstract

Sulfo Lewis^x analog containing 1-deoxynojirimycin (13) has been efficiently synthesized. Glycosidation of ethyl 2,3,4-tri-O-benzyl-1-thio-β-D-fucopyranoside (5) with O-2,6-di-O-benzoyl-3,4-isopropylidene-β-D-galactopyranosyl)-(1→4)-2,6-di-O-benzoyl-N-benzyloxycarbonyl-1,5-dideoxy-1,5-imino-D-glucitol (4), prepared from O-β-D-galactopyranosyl-(1→4)-1,5-dideoxy-1,5-imino-D-glucitol (1) via 3 steps, and subsequent acid hydrolysis of the isopropylidene group gave the desired trisaccharide diol derivative (7) in good yield. Compound 7 was easily converted into 3′-O-sulfo Lewis^x analog (13) via 6 steps in high yield.

     

Convergent synthesis of a common pentasaccharide-repeating unit corresponding to the O-specific polysaccharide of Escherichia coli O4:K3, O4:K6, and O4:K12

A convergent chemical synthesis of a pentasaccharide found in the O-specific polysaccharide of Escherichia coli O4:K3, O4:K6, and O4:K12 has been achieved in excellent yield. A [3+2] block synthetic strategy has been adopted to couple a disaccharide donor 11 with a trisaccharide acceptor 10 for the construction of the pentasaccharide derivative 12 which on deprotection furnished target pentasaccharide 1 as its 4-methoxyphenyl glycoside. Disaccharide thioglycoside donor 11 and trisaccharide acceptor 10 were prepared from suitably protected monosaccharide intermediates. Yields were excellent in all steps.     

New synthesis of idraparinux,the non-glycosaminoglycan analogue of the antithrombin-binding domain of heparin

Idraparinux, the fully O-sulfated, O-methylated, heparin-related pentasaccharide possessing selective factor Xa inhibitory activity, was prepared by a new synthetic pathway. This route was based on a [2+3] block synthesis utilizing a 6-O-silyl-protected l-idose-containing trisaccharide acceptor, which was glycosylated with a disaccharide donor containing a non-oxidized precursor of the glucuronic acid. The unique strategy of multiple functionalizations at pentasaccharide levels, involving triple methylation followed by oxidation of the glucose and the idose precursors into d-glucuronic and l-iduronic acids in one step, proved to be highly efficient, providing the target pentasaccharide through a 39-step synthesis starting from d-glucose and methyl α-d-glucopyranoside.     

Synthesis of tri- and pentasaccharide fragments corresponding to the O-antigen of Shigella boydii type 6

A convenient synthetic strategy for the synthesis of the acidic pentasaccharide repeating unit and its trisaccharide fragment corresponding to the O-antigen of Shigella boydii type 6 has been successfully developed. A stereoselective sequential glycosylation method has been exploited to obtain the target tri- and pentasaccharide derivatives. Most of the synthetic intermediates were solid and prepared in high yields from commercially available reducing sugars following a series of protection–deprotection reactions. A late-stage TEMPO mediated selective oxidation reaction finally resulted in the pentasaccharide containing a glucuronic acid unit. A 2-(4-methoxyphenoxy) ethyl group has been chosen as the anomeric protecting group to provide trisaccharide and pentasaccharide derivatives linked to an ethylene glycol linker.     

Synthesis and NMR spectroscopic analysis of acylated pentasaccharide fragments of mycobacterial arabinogalactan

The mycolyl-arabinogalactan (mAG) complex, a large glycolipid composed of arabinofuranose and galactofuranose monosaccharides and mycolic acid lipids, provides mycobacteria with substantial protection from their environment. It has been proposed that the presence of flexible furanose rings in the mAG facilitates the packing of the hydrophobic mycolic acids, forming a dense protective barrier of low permeability. In a previous article, we probed this "flexible scaffold hypothesis" through the synthesis and NMR analysis of di- and trisaccharide fragments of the mAG acylated with linear fatty acids. However, we saw few conformational changes due to the presence of the acyl chains. We proposed that branched pentasaccharide glycolipids 5-8 might exhibit larger changes due to the presence of more acyl chains, and studies with these compounds are described here. The carbohydrate portion of 5-8 was synthesized in a 1 + 2 + 2 manner. First, the monosaccharide diol was treated with an excess of appropriately protected thioglycoside donor to give a trisaccharide, which, following selective deprotection to a diol, was converted to the pentasaccharide in a one-pot glycosylation. The resulting differentially protected pentasaccharide 20 gave glycolipids 5-8 upon removal of the protecting groups at the primary positions, acylation, and hydrogenolysis. The conformations of 5-8 were probed using NMR spectroscopy, and chemical shift selective filtering 1D-TOCSY spectra allowed for the determination of all the ring coupling constants. It was found that the addition of four fatty acids to the parent pentasaccharide had little effect on the conformation of the compounds in solution.     

First Total Synthesis of Trehalose‐Containing Branched Oligosaccharide OSE‐1 of Mycobacterium gordonae (Strain 990)

The first total synthesis of the branched oligosaccharide OSE‐1 of Mycobacterium gordonae (strain 990) is reported. An intramolecular aglycon delivery approach was used for constructing the desymmetrized 1,1′‐α,α‐linked trehalose moiety. A [3+2] glycosylation of the trisaccharide donor and trehalose acceptor furnished the right hand side pentasaccharide. Regioselective O3 glycosylation of L ‐rhamnosyl 2,3‐diol allowed expedient synthesis of the left hand side tetrasaccharide. The nonasaccharide was assembled in a highly convergent fashion through a [4+5] glycosylation.     

Amidoglycosylation of Polymer-Bound Glycals: A Complete Solid-Phase Synthesis of the Oligosaccharide Domain of the Lewisb Blood Group Determinant

A new general method for the preparation of N-acetylglucosamine glycosidic linkages has been developed for solid-phase synthesis. The complete pentasaccharide domain of the Lewis^b blood group antigen, which is a mediator in the formation of ulcers and gastric cancer, has now been synthesized on solid support (see 1 ; the shaded circle is the polystyrene support; TIPS=triisopropylsilyl).     

Synthesis of a new glycosphingolipid from the marine ascidian Microcosmus sulcatus using a one-pot glycosylation strategy

A novel neutral glycosphingolipid found in Microcosmus sulcatus containing a β-d-Galp(1→4)[α-d-Fucp-(1→3)]β-d-Glcp-(1→)Cer motif was synthesized. Trisaccharide derivatives were synthesized using trimethylsilyltrifluoromethanesulfanate (TMSOTf) and N-iodosuccimide (NIS)/trifluoromethane sulfonic acid (TfOH) as the promoters. Synthesis was achieved with an efficient one-pot glycosylation strategy. This is the first report of a one-pot glycosylation strategy using the procedure of Boons et al. for the synthesis of a natural product. Coupling of trisaccharide derivative 19 and ceramide derivative 20 by TMSOTf afforded the glycosphingolipid derivative 21. The fully protected glycoside was deprotected to give the target glycosphingolipid 2.     

Synthesis of three regioisomers of the pentasaccharide part of the Skp1 glycoprotein of Dictyostelium discoideum

Three regioisomers of the linear pentasaccharide part of the Skp1 glycoprotein, found in Dictyostelium discoideum, were prepared in the form of (2-trimethylsilyl)ethyl glycosides by means of 2+3 block syntheses using the disaccharide donor at the non-reducing end, and three different trisaccharide acceptors at the reducing end. Fucosylation of (2-trimethylsilyl)ethyl 3,4,6-tri-O-benzyl-β-d-galactopyranosyl-(1→3)-4,6-O-benzylidene-2-deoxy-2-NPhth-β-d-glucopyranoside with different fucosyl donors carrying an O-(2-naphthyl)methyl ether as a temporary-protecting group at positions C2, C3 or C4 gave rise to the protected core trisaccharides. After selective removal of the (2-naphthyl)methyl group, the resulting acceptors were glycosylated with the α(1→6) linked digalactosyl donor to yield the respective three regioisomeric pentasaccharides. Transformation of the phthalimido moiety into an N-acetyl group, followed by catalytic hydrogenation of the reducible-protecting groups furnished the free target pentasaccharides, which should be able to assist during the elucidation of the exact structure of the natural pentasaccharide.     

Structural and P NMR investigation of Bi(MM′)2PO6 statistic solid solutions: Deconvolution of lattice constraints and cationic influences

Two solid solutions BiM_xMg_(2−x)PO₆ (with M²⁺=Zn or Cd) have been studied through ³¹P MAS NMR. The analysis has been performed on the basis of refined crystal structures through X-ray diffraction and neutron diffraction. The BiZn_xMg_(2−x)PO₆ does not provide direct evidence for sensitive changes in the phosphorus local symmetry. This result is in good agreement with structural data which show nearly unchanged lattices and atomic separations through the Zn²⁺ for Mg²⁺ substitution. On the other hand, the Cd²⁺ for Mg²⁺ substitution behaves differently. Indeed, up to five resonances are observed, each corresponding to one of the five first-cationic neighbour distributions, i.e. 4Mg/0Cd, 3Mg/1Cd, 2Mg/2Cd, 1Mg/3Cd and 0Mg/4Cd. Their intensities match rather well the expected weight for each configuration of the statistical Cd²⁺/Mg²⁺ mixed occupancy. The match is further improved when one takes into account the influence of the 2nd cationic sphere that is available from high-field NMR data (18.8 T). Finally, the fine examination of the chemical shift for each resonance versus x allows to de-convolute the mean Z/a² effective field into two sub-effects: a lattice constraint-only term and a chemical-only term whose effects are directly quantifiable.     

Synthesis of benzaldehyde-functionalized LewisX trisaccharide analogs for glyco-SAM formation

LewisX (Le^x) antigen based carbohydrate–carbohydrate interactions are mediated by complexation of metal ions. Although theoretical studies about the influence of participating hydroxyl groups in the Le^x trisaccharide head group (Galβ(1-4)[Fucα(1-3)]GlcNAc) could gave same rudimental information about the basic mechanism behind this interaction, a little is known about orientation and configuration of the hydroxyl groups required for the specific interaction mediated by Ca²⁺ complexation. Therefore, there is a need of non-natural derivatives to provide detailed information about the requirements for hydroxyl group arrangement in Le^x head group surface plasmon resonance and gold nanoparticle techniques have shown to be powerful tools to investigate carbohydrate–carbohydrate interactions. Benzaldehyde-functionalized glycans can be used for attachment to both gold nanoparticles and surface plasmon resonance sensor surfaces. Therefore, seven benzaldehyde equipped Le^x analogs including the natural trisaccharide were synthesized utilizing convergent approach. The derivatives were applied in ongoing carbohydrate–carbohydrate interaction studies by surface plasmon resonance experiments to prove theoretical postulate about the structural requirements of hydroxyl group arrangements in Le^x trisaccharides.     

Vacancy ordering and oxygen dynamics in oxide ion conducting La1−xSrxGa1−xMgxO3−x ceramics: Ga, Mg and O NMR

The oxygen vacancies distribution in the rigid lattice and the thermally activated motion of oxygen atoms are studied in La_1−xSr_xGa_1−xMg_xO_3−x (x=0.00; 0.05; 0.10; 0.15 and 0.20) compounds. For that ⁷¹Ga, ²⁵Mg and ¹⁷O NMR was performed from 100 K up to 670 K, and ion conductivity measurements were carried out up to 1273 K. The comparison of the electric field gradients at the Ga- and Mg-sites evidences that oxygen vacancies appear exclusively near gallium cations as a species trapped below room temperature in local clusters, GaO_5/2-□-GaO_5/2. These clusters decay at higher temperature into mobile constituents of the structural octahedra Ga(O_5/6□_1/6)_6/2. At the same time, the nearest octahedral oxygen environment of magnesium cations persists at different doping levels. The case of two adjacent vacant anion sites is found highly unlikely within the studied doping range. The thermally activated oxygen motion starts to develop above room temperature as is observed from both the motional narrowing of ¹⁷O NMR spectra and the ¹⁷O nuclear spin-lattice relaxation rate. The obtained results show that two types of motion exist, a slow motion and a fast one. The former is a long-range diffusion whereas the latter is a local back and forth oxygen jumps between two adjacent anion sites. These sites are strongly differentiated by the probability of the vacancy formation, like the vacant apical site and the occupied equatorial site in the orthorhombic compositions x <0.15.     

(p-Sulfomethyl)phenylalanine as a mimic of O-sulfatyl-tyrosine in synthetic partial sequences of P-Selectin glycoprotein ligand 1 (PSGL-1)

Fmoc-l-(p-sulfomethyl)phenylalanine, a bioisosteric mimic of acid-sensitive O-sulfatyl tyrosine, was synthesized from l-tyrosine according to a novel route. Partial sequences of the recognition site of P-Selectin glycoprotein ligand 1 (PSGL-1), which contain (sulfomethyl)phenylalanine were synthesized on solid-phase. By fragment condensation, a sialyl Lewis^x peptide conjugate containing a (sulfomethyl)phenylalanine mimic of O-sulfatyl tyrosine was prepared without destruction of the acid-sensitive fucoside bond within the saccharide side chain. Compounds of this type are of interest as sufficiently acid-stable potential inhibitors of P-Selectin in inflammatory processes.     

Stereoselective synthesis of 1,2-cis galactosides: synthesis of a glycolipid containing Galα1-6Gal component from Zygomycetes species

An α-selective galactosylation was demonstrated under various conditions. Among these α-galactoside approaches, high α-selectivity was achieved by the virtue of 4,6-O-di-tert-butylsilylene (DTBS) group. Yield was further improved by the influence of a 2-O-benzylated donor compared to 2-O-benzoylated donor. This method was then applied to the first highly stereoselective synthesis of a newly found trisaccharide glycosphingolipid in Zygomycetes species.     

Galactosidase-Assisted Synthesis En Route to Type I And Type II Structures of Chitooligomers

ABSTRACT

Transgalactosylation of chitobiose and chitotriose led to formation of terminally (β1-3)- and (β1-4)-galactosylated chitooligosaccharides ready for fucosylation to give Lewis^a and Lewis^x motifs. Their structures could be assigned employing HPAECPAD, methylation, ESI-MS/MS and NMR analyses.     

N-连接的糖蛋白核心甘露五糖及其异构体的合成研究

以1,2-O-亚乙基-4,6-O-亚苄基-β-D-甘露糖(2)和2,3,4,6-四-O-苯甲酰基-α-D-甘露吡喃糖基三氯乙酰亚胺酯(3)为基本原料，经一些简单的化学转换和选择性的糖基化反应，得到了甘露核心五糖及其异构体。