NMR study of hydroxy protons of di- and trimannosides, substructures of Man-9

The chemical shifts, temperature coefficients and inter-residual rotating-frame Overhauser effect (ROE)s for the hydroxy protons of some alpha-(1,2)-, alpha-(1,3)- and alpha-(1,6)-linked di- and trimannosides have been measured for samples in 85% H2O/15% acetone-d6 solution. These mannosides, Manalpha(1-->2)ManalphaOMe (1) Manalpha(1-->3)ManalphaOMe (2), Manalpha(1-->6)ManalphaOMe (3), Manalpha(1-->2)Manalpha(1-->2)ManalphaOMe (4), Manalpha(1-->2)Manalpha(1-->3)ManalphaOMe (5), Manalpha(1-->2)Manalpha(1-->6)ManalphaOMe (6) and Manalpha(1-->3)[Manalpha1-->6]ManalphaOMe (7), are substructures of the N-glycan Man-9.The NMR data show that the hydration of each individual hydroxyl group in the di- and trisaccharides is very similar to the hydration of the corresponding hydroxyl in the monomeric methyl alpha-D-mannoside. No hydrogen-bond interactions were found to stabilize the conformations of the alpha-(1,2)- and alpha-(1,6)-linkages and the chemical shifts for the hydroxy proton resonances of the alpha-(1,6)-linkage indicated high-conformational flexibility. For the alpha-(1,3)-linkage, however, the downfield shift for the signal of O(2)H of the 3-substituted residue together with the ROE between this proton and H5' on the next residue suggest some weak inter-residue interactions.     

Synthesis of highly branched oligomannosides

Helferich glycosylation of 1,2-O-[(1-cyano)ethylidene]-β-d-mannopyranose with acetobromomannose results in selective 3,6-bis-glycosylation of the acceptor. The peracetylated trisaccharide cyanoethylidene derivative is an efficient glycosyl donor, which is exemplified by preparation of a branched tetrasaccharide.     

A one-pot strategy for synthesis of 5-O-(alpha-D-arabinofuranosyl)-6-O-(beta-D-galactofuranosyl)-D-galactofuranose present in motif E of the Mycobacterium tuberculosis cell wall

5-O-(Alpha-D-arabinofuranosyl)-6-O-(beta-D-galactofuranosyl)-D-galactofuranose 6 present in motif E of the Macobacterium tuberculosis cell wall has been regio- and stereospecifically synthesized using 3-O-benzoyl-1,2-O-isopropylidine-alpha-D-galactofuranose (10) as the glycosyl acceptor by the trichloroacetamidate method in a one-pot manner. The diol glycosyl acceptor 10 was smoothly derived from 1,2:5,6-di-O-isopropylidene-alpha-D-galactofuranose (8) by 3-O-benzoylation and then selective 5,6-O-deacetonation. The preparation of 8 was greatly improved by increasing the ratio of DMF to acetone and using a solid-supported catalyst.     

Highly Regio- and Stereoselective Synthesis of Mannose-Containing Oligosaccharides with Acetobromo Sugars as the Donors and Partially Protected Mannose Derivatives as the Acceptors via Sugar Orthoester Intermediates

An orthoester formation/rearrangement sequence , in which 1,2-O-ethylidenated mannose or partially protected mannosides function as the glycosyl acceptors and simple acetobromo sugars as the glycosyl donors (see reaction scheme), provides an efficient and highly regio- and stereoselective route to mannose-containing 1→6, 1→3, and 3,6-branched oligosaccharides with exclusive 1,2-trans linkage.     

N-benzyl-2,3-oxazolidinone as a glycosyl donor for selective alpha-glycosylation and one-pot oligosaccharide synthesis involving 1,2-cis-glycosylation

Glycosylation reactions using N-benzyl-2,3-trans-oxazolidinones as the glycosyl donors were shown to be highly alpha-selective. Advantages of the donor include facile preparation in gram-scale preparation and simple deprotection procedures. Subsequently, a one-pot oligosaccharide synthesis involving 1,2-cis glycosidic linkages was demonstrated using the novel glycosyl donors.     

Facile preparation of the oxetane-nucleosides

Efficient and practical large scale synthesis of suitably protected 1',2'-oxetane locked purine and pyrimidine nucleosides for incorporation in oligo-DNA or -RNA by solid-phase synthesis is reported. A high regio and stereoselectivity with preferential formation of the beta-anomer in the glycosylation reaction, using the Vorbrüggen procedure, was achieved by a convergent synthetic procedure with orthogonal protection strategy using either 1,2-di-O-acetyl-3,4-O-isopropylidene-6-O-(4-toluoyl)-d-psicofuranose or 2-O-acetyl-6-O-benzyl-1,3,4-tri-O-(4-toluoyl)-d-psicofuranose as the glycosyl donor.     

Completely β-selective glycosylation using 3,6-O-(o-xylylene)-bridged axial-rich glucosyl fluoride

A completely β-selective glycosylation that does not rely on neighboring group participation is described. The novelty of this work is the design of the glycosyl donor locked into the axial-rich form by the o-xylylene bridge between the 3-O and 6-O of d-glucopyranose. The synthesized 2,4-di-O-benzyl-3,6-O-(o-xylyene)glucopyranosyl fluoride could efficiently react with various alcohols in a SnCl(2)-AgB(C(6)F(5))(4) catalytic system. The mechanism composed of the glycosylation and isomerization cycles was revealed through comparative experiments using acidic and basic molecular sieves. The achieved perfect stereocontrol is attributed to the synergy of the axial-rich conformation and convergent isomerization caused by HB(C(6)F(5))(4) generated in situ.     

Efficient synthesis of Man2, Man3, and Man5 oligosaccharides, using mannosyl iodide donors

[reaction: see text] A highly efficient protocol for making Man(3) and Man(5) oligosaccharides with use of orthogonally protected glycosyl iodide donors has been developed. Glycosylation of a C-2-O-acetyl mannosyl iodide donor in the presence of silver triflate at -40 degrees C initially gave a mixture of the desired alpha-linked mannoside and an orthoacetate resulting from attack at the C-2 acetate. However, upon warming to room temperature the orthoacetate quantitatively rearranged to the desired oligosaccharide. Employing a 3,6-dihydroxy acceptor and subjecting it to double glycosidation quickly afforded high mannose sugars in nearly quantitative yields. Glycosyl iodide donors offer advantages over previously reported chloride donors as the reactions are faster, proceed in higher yields, and are not diminished in higher order constructs. These studies continue to dispel the notion that glycosyl iodides are too reactive to be of synthetic utility.     

Glycal scavenging in the synthesis of disaccharides using mannosyl iodide donors

[reaction: see text] High mannose glycans composed of alpha (1-->2) and alpha (1-->6) branched sugars are important components of the HIV-associated envelope glycoprotein, gp120. These substructures can be efficiently prepared in solution from glycosyl iodide precursors requiring only a slight excess of the iodide donor, which offers advantages over solid-phase methods that require more than 5 equiv of donor. During the reaction, excess iodide is converted to a glycal that is not easily separated from the desired disaccharide. To overcome this difficulty, a phase-trafficking methodology that relies upon nucleophilic interception of the 1,2 anhydrosugar resulting from oxidation of the glycal has been developed.     

Regioselective glycosylation of 3,6-unprotected mannoside derivatives: fast access to high-mannose type oligosaccharides

A regioselective glycosylation of 3,6-unprotected mannoside acceptors was investigated. With glycosyl trichloroacetimidate donors, when an excess of trimethylsilyl trifluoromethanesulfonate is used as the catalyst, 6-O-glycosylation exclusively occurred affording a silylated disaccharide that could be involved in a subsequent glycosylation reaction. As an illustration, the fast synthesis of two trisaccharides and one pentasaccharide was achieved.     

Study of carbohydrate-carbohydrate interactions: total synthesis of 6d-deoxy Lewis pentaosyl glycosphingolipid

This article describes total synthesis of 6d-deoxy Lewis^x pentaosyl glycosphingolipid, a useful tool for study of the Lewis^x-Lewis^x interaction. A 6-deoxy galactose donor was condensed with a diol of glucosamine to provide regioselectively a β 1→4 linked disaccharide, which was further fucosylated to a protected deoxy Lewis^x trisaccharide. Glycosylation of a lactoside diol with the 6d-deoxy Lewis^x trisaccharide gave regio- and stereoselectively a pentasaccharide in excellent yield. After chemical modification, this pentasaccharide reacted with the 3-O-benzoylated azidosphingosine to form a glycosphingolipid, which, after azide reduction followed by condensation with stearic acid and deprotection, afforded the target compound.     

Synthesis of Oligosaccharide Structures from the Lipopolysaccharide of Moraxella catarrhalis

The synthesis of the octasaccharide [p-(trifluoroacetamido)phenyl]ethyl 4-O-[2-O-(2-acetamido-2-deoxy-alpha-D-glucopyranosyl)-beta-D-glucopyranosyl]-6-O-[2-O-[4-O-(4-O-alpha-D-galactopyranosyl-beta-D-galactopyranosyl)-alpha-D-glucopyranosyl]-beta-D-glucopyranosyl]-3-O-beta-D-glucopyranosyl-alpha-D-glucopyranoside, representing the outer part of the lipooligosaccharide from Moraxella catarrhalis serotype A, is described, together with a hepta-, a hexa-, and a pentasaccaride, composing parts thereof with shorter oligosaccharide chains substituted in the 6-position of the central 3,4,6-branched glucose moiety. The versatility of the use of thioglycosides in oligosaccharide synthesis is shown, since throughout the synthesis thioglycosides are used as glycosyl donor precursors, either directly in dimethyl(methylthio)sulfonium triflate (DMTST)-promoted coupling reactions or after conversion to the corresponding glycosyl bromide in silver triflate-promoted couplings. The effects of different protecting groups, anomeric leaving groups, and solvents used in the various coupling reactions are often substantial, which necessitates the use of easily convertible intermediates.     

First synthesis of an α-d-Fucp3NAc containing oligosaccharide: a study on d-Fucp3NAc glycosylation

3-Acetamido-3,6-dideoxy-d-galactopyranose (d-Fucp3NAc) is an aminosugar almost exclusively found in phytopathogenic O-antigens. The glycosylation reaction involving d-Fucp3NAc donors was studied with several rhamnosyl acceptors, revealing that the best yields and highest α-stereoselectivity were obtainable by coupling a N-phenyl trifluoroacetimidate glycosyl donor in a ternary mixture (dioxane/DME/toluene 4:1:1) as solvent. For the first time a synthetic access to α-d-Fucp3NAc containing oligorhamnans, that are interesting molecules for studying the effects of O-antigen model oligosaccharides on the modulation of plant response to bacteria, was reported. An example is the pentasaccharide repeating unit of the major O-antigen component from Pseudomonas syringae pv. holci IMV 8300, which was synthesized as its methyl glycoside.     

Stereoselective synthesis of the 3,6-branched Fuzi α-glucans up to 15-mer via a one-pot and convergent glycosylation strategy

A family of the 3,6-branched Fuzi α-glucans including the pentasaccharide repeating unit as well as its di- and trimers were efficiently achieved via a one-pot and convergent glycosylation strategy. All the protected α-glucans up to 15-mer were assembled with high yields and excellent α-stereoselectivity, which was secured by the synergistic α-directing effects of the TolSCl/AgOTf promotion system and the steric β-facial shielding of bulky saccharide residues linked at the 6-O-position of glucosyl donors. Moreover, the 3,6-branched architecture of glycosyl donor was revealed to be more favorable for the α-selective glucosidation of primary hydroxyl group, especially in the case of large oligosaccharide acceptor. The structurally well-defined synthetic α-glucans would be useful for various biological studies.     

A practical route to 3,6-dideoxyhexoses

Novel, readily scaled and practical routes for the synthesis of 3,6-dideoxy-d-xylo-hexose and 3,6-dideoxy-d-ribo-hexose and their corresponding glycosyl donors are presented. The method uses a 1,2-O-propylidene acetal to protect the monosaccharides, glucose and galactose, thereby permitting not only easy modification at both 3 and 6 positions, but also the opportunity to readily place different protecting groups on OH-2 and OH-4.     

Antiallergic agent from natural sources. 2. Structures and leukotriene release-inhibitory effect of torososide B and torosachrysone 8-O-6"-malonyl beta-gentiobioside from Cassia torosa Cav.

Two new anti-allergic compounds, torososide B and torosachrysone 8-O-6"-malonyl gentiobioside were isolated from the seeds of Cassia torosa Cav., and their structures were established as physcion 8-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl- (1-->3)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside and torosachrysone 8-O-beta-D-glucopyranosyl-(1-->6)-6-malonyl beta-D-glucopyranoside on the basis of spectral and chemical evidence. Torososide B and torosachrysone 8-O-6"-malonyl gentiobioside were found to inhibit the release of leucotrienes from rat peritoneal mast cells induced by calcium ionophore A 23187.     

Synthesis and study of hexanuclear molybdenum clusters containing thiolate ligands

Four hexanuclear molybdenum chloride cluster complexes containing terminal thiolate ligands have been synthesized and fully characterized. (Bu 4N) 2[Mo 6Cl 8(SEt) 6] was prepared by reacting Na 2[Mo 6Cl 8(OMe) 6] with an excess of ethanethiol in refluxing tetrahydrofuran. (PPN) 2[Mo 6Cl 8(SBu) 6], (Bu 4N) 2[Mo 6Cl 8(SBn) 6], and (Bu 4N) 2[Mo 6Cl 8(SNC 8H 6) 6] (C 8H 6NS (-) = 3-indolylthiolate) were subsequently prepared in the reaction of [Mo 6Cl 8(SEt) 6] (2-) with an excess of HSR (R = Bu, Bn or 3-indolyl). Single crystal X-ray diffraction analyses were performed on two of these complexes: (PPN) 2[Mo 6Cl 8(SEt) 6].Et 2O, crystallizes in the triclinic space group P1 with a = 12.3894(11), b = 13.7651(12), c = 15.0974(13), alpha = 103.975(2), beta = 99.690(2), gamma = 98.062(2), and Z = 1; (PPh 3Me) 2[Mo 6Cl 8(SBn) 6].2NO 2CH 3, also crystallizes in the P1 space group with a = 12.1574(16), b = 13.4441(17), c = 14.2132(18), alpha = 89.654(2), beta = 88.365(2), gamma = 71.179(2), and Z = 1. Our studies demonstrate that [Mo 6Cl 8(SEt) 6] (2-) displays luminescent properties and that the same complex undergoes substitution reactions with different thiols, as well as reaction with electrophilic reagents such as MeI.     

Functionalized derivatives of sterically hinderedo-quinones and pyrocatechols. 3,6-di-tert-butyl-4-dicyanometyl-1,2-benzoquinone and its isomers

Base-catalyzed interaction of 3,6-di-tert-butyl-1,2-benzoquinone with malononitrile mainly occurs as 1,4-addition to give 3,6-di-tert-butyl-4-dicyanomethylpyrocatechol. Its oxidation leads to 3,6-di-tert-butyl-4-dicyanomethyl-1,2-benzoquinone, which converts into 3,6-di-tert-butyl-2-hydroxy-α,α-dicyano-1,4-quinomethane in solution and in the solid state. The latter rearranges into isomeric 3,6-di-tert-butyl-5-dicyanomethylenecyclohex-3-ene-1,2-dione. Reverse conversion occurs under the action of amines. Semiquinone complexes of dicyanomethylquinone were studied in solutions by ESR.     

A new unsaturated glycoglycerolipid from a cultured marine dinoflagellate Amphidinium carterae

From the cultured marine dinoflagellate Amphidinium carterae, a new unsaturated glycoglycerolipid (2S)-1,2-O-6,9,12,15-dioctadecatetraenoyl-3-O-[alpha-D-galactopyranosyl-(1'-->6')-O-beta-D-galactopyranosyl]-glycerol (1), has been isolated together with two known saturated ones, (2S)-1,2-distearoyl-3-O-(6-sulpho-alpha-D-quinovopyranosyl)-glycerol (2) and (2S)-1-stearoyl-3-O-(6-sulpho-alpha-D-quinovopyranosyl)-glycerol (3). Their structures were elucidated on the basis of chemical and spectral data.     

Glycosylation with 1,2-Anhydromannofuranose Benzyl Ether as the Glycosyl Donor: A Comparison Between Sugar Pyranose and Furanose Acceptors for their Primary Hydroxy Activity

ABSTRACT

Some 1→5 and 1→6 α-linked furano-disaccharide derivatives were synthesized using 1,2-anhydromannofuranose as the glycosyl donor. Comparison of the glycosyl acceptors indicated that the activity of primary hydroxyl groups of glycofuranoses was much lower than that of glycopyranoses.