Methyl Glycosides Research Articles

The Addition of Malonates to Glycals: A General and Convenient Method for the Synthesis of 2-C-Branched Carbohydrates

A general and convenient synthesis of carbohydrate 2-C-analogs by addition of malonates to glycals is described. The method is applicable to glycals derived from hexoses and pentoses and is characterized by easily available precursors. The reactions are mediated by manganese(III) or cerium(IV) and proceed via intermediarily generated malonyl radicals. All additions exhibit a very high degree of regioselectivity, since only 2-C-branched sugars were obtained. This result can be best rationalized by favorable orbital interactions between the SOMO of the malonyl radical and the HOMO of the double bond. Variation of the steric demand of the malonate or the glycal allows the stereoselectivities to be increased up to >98%. Highest selectivities were obtained with tri-O-acetyl-d-galactal and di-O-acetyl-d-arabinal, where the attack occurs exclusively from one face of the carbohydrate. For all cerium(IV)-mediated reactions, methyl glycosides are formed as main products in 73−89% yield, which can be isolated in analytically pure form on a gram scale. Strong evidence was found for a ligand transfer rather than electron transfer during the formation of carbohydrate 1-nitrates, which sheds light on the mechanism of transition-metal-mediated radical reactions. In terms of starting materials, stereoselectivities, and yields, the herein described method for the synthesis of carbohydrate 2-C-analogs is superior to literature known procedures.

ChemInform Abstract: Chemistry of Glucal Halohydrins. Part 2. An Unusual Protecting Group Effect in the Competitive Formation of Formyl Furanosides and Methyl Glycosides.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Selective binding of N-acetylglucosamine to the chicken hepatic lectin.

Among Ca2+-dependent (C-type) animal lectins, the chicken hepatic lectin (CHL) is unique in displaying almost complete selectivity for N-acetylglucosamine over other monosaccharide ligands. The crystal structures of the carbohydrate-recognition domain (CRD) from serum mannose-binding protein (MBP) and of a complex between the CRD from liver MBP and the methyl glycoside of N-acetylglucosamine were used to model the binding site in CHL. Substitution of portions of CHL into the MBP framework did not substantially increase selectivity. A bacterial expression system for the CRD of CHL was developed so that specific residues predicted to be near the 2-acetamido substituent of N-acetylglucosamine could be altered by site-directed mutagenesis. The results indicate that the ligand is bound to CHL in the same orientation as it binds to liver MBP. A tyrosine and a valine residue that probably contact the the N-acetyl group have been identified. These results, together with studies of ligand-binding selectivity, suggest that these residues form part of a binding pocket for the N-acetyl group, which confers selective binding of N-acetylglucosamine.

β-Mannanolytic system of Aureobasidium pullulans

A xylanolytic yeast strain Aureobasidium pullulans NRRL Y 2311-1, was found to produce all enzymes required for complete degradation of galactomannan and galactoglucomannan. The enzymes differed in function and cellular localization: endo-β-1,4-mannanase was secreted into the culture fluid, β-mannosidase was strictly intracellular, and α-galactosidase and β-glucosidase were found both extracellularly and intracellularly. Among these enzyme components, only extracellular β-mannanase and intracellular β-mannosidase were inducible. The production of β-mannanase and β-mannosidase was 10- to 100-fold higher in galactomannan medium than in medium with one of the other carbon sources. β-mannanase and β-mannosidase were coinduced in glucose-grown cells by galactomannan, galactoglucomannan, and β-1,4-manno-oligosaccharides. The natural inducer of extracellular β-mannanase and intracellular β-mannosidase appeared to be β-1,4-mannobiose. Synthesis of both enzymes was completely repressed by glucose, mannose, or galactose. The synthetic glycoside methyl β-d-mannopyranoside served as a nonmetabolizable inducer of both β-mannosidase and β-mannanase.

Chemistry of glucal halohydrins(II): An unusual protecting group effect in the competitive formation of formyl furanosides and methyl glycosides

A remarkable protecting group influence was observed in the base-induced reaction of protected halohydrins derived from d-glycals. Tri- O-methyl and tri- O-benzyl halohydrins react with cesium carbonate in methanol at room temperature to give methyl glycosides as the major product and unsaturated formyl furanosides as the minor product. Whereas, the tri- O- tert-butyldimethylsilyl ( t-BuMe 2Si)-protected halohydrins reacted with cesium carbonate in methanol at room temperature to give a mixture of epimeric formyl furanosides, and at reflux to give an unsaturated formyl furanoside, as the only products. The tri- O-methyl and tri- O-benzyl halohydrins react slowly at elevated temperature to give predominantly furans. In comparison, the tri- O- t-BuMe 2Si halohydrins reacted completely after five minutes to give a mixture of epimeric formyl furanosides. The tri- O- t-BuMe 2Si iodohydrins were oxidized to the corresponding iodolactones, which also underwent a based-induced ring contraction in methanol to give the furanose 1-methylcarboxylate esters.

Synthesis of a Trisaccharide Repeating Unit Related to Arabinogalactan-Protein (AGP) Polysaccharides1

Starting from L-arabinose and methyl β-D-galactopyranoside, methyl 2,3,4-tri-O-benzyl-6-O-[2,4,6-tri-O-benzoyl-3-O-(23,5-tri-O-benzoyl-α-L-arabinofuranosyl)-β-D-galactopyranosyl]-β-D-galactopyranoside 10 has been synthesized. Removal of protecting groups gave the methyl glycoside 12 of a trisaccharide representative of a repeating unit of arabinogalactan (AGP) polysaccharides. 1. Presented at the XVIIIth International Carbohydraie Symposium, Milan, Italy, July 2 1-26, 1996.

Reactions of 1,6-anhydro-3,4-dideoxy-2-O-methyl-β-d-threo-hex-3-enopyranose with thiols and methanol

Thiolysis and methanolysis of 1,6-anhydro-3,4-dideoxy-2-O-methyl-β-d-threo-hex-3-enopyranose yield anomeric thio- and methyl glycosides, respectively, and an acyclic product (in the reaction with EtSH).

Synthesis of the monosaccharide units of the O-specific polysaccharide of Shigella sonnei

The monosaccharide components of the O-specific polysaccharide 1 of the lipopolysaccharide of the enteropathogenic bacterium Shigella sonnei were synthesized as their methyl glycosides 2 and 3 in their natural anomeric form. The key intermediate to the diaminotrideoxygalactose derivative 2 was ethyl 3-O-acetyl-2-deoxy-2-phthalimido-1-thio-β-d-glucopyranoside (9) that was converted to its ditosylate 10. Regioselective deoxygenation at C-6 followed by nucleophilic displacement of the secondary tosyloxy group by azide afforded the 4-azido thioglycoside 13. Methyl trifluoromethanesulfonate-assisted methanolysis of 13 gave the O-glycoside 14. Replacement of the phthalimido by an acetamido group followed by catalytic reduction of the azido group led to the diamino-trideoxygalactose derivative 2. The precursor to the l-altruronic acid derivative 3 was methyl α-l-glucopyranoside (19) that was routinely converted to the benzylidene-protected 2,3-anhydro-allopyranoside 22. Regioselective opening of the epoxide ring by NaN3 afforded the 2-azido derivative 23 that was benzylated at HO-3. Hydrolytic removal of the benzylidene group followed by TEMPO oxidation of C-6 and subsequent esterification with MeI gave the key l-azido-altruronic acid intermediate 29 that was transformed to the acetamidoaltruronic acid derivative 3. High resolution NMR data of the altruronic acid derivatives indicate that the conformation of their pyranose ring is crucially dependent on the substitution pattern: the 2-azido altruronic acid derivatives prefer the 4C1 conformation whereas the 2-acetamido congeners exist preferentially in the 1C4 conformation.

Synthesis of the 2‐Deoxyisomaltose Analogue of Acarbose by an Improved Route to Chiral Valieneamines

AbstractA 2‐deoxyisomaltose analogue of acarbose was stereoselectively synthesised in 11 steps with a total yield of 7% starting from 2,6‐dibromo‐2, 6‐dideoxy‐D‐mannono‐1,4‐lactone (6). The latter was reduced to the lactol, converted to the methyl glycoside (7) and hydrogenated to the methyl 6‐bromo‐2,6‐dideoxyglycoside (8). Benzylation of the hydroxy groups, elimination of bromine to a 5‐ene and Ferrier carbocyclisation gave (2S, 3R)‐2,3‐bisbenzyloxycyclohex‐5‐enone (12). 1, 2‐addition of benzyloxymethyl lithium at –110°C gave a 6:1 mixture of tertiary alcohols 13; the (1S) isomer was the major one. Reaction with trichloroacetyl isocyanate gave a carbamate 19, which, when dehydrated to the cyanate, spontaneously underwent [1,3] sigmatropic rearrangement to an isocyanate, which on addition of methanol gave the methylcarbamate 20. Basic hydrolysis of this compound gave (2R, 3R,5R)‐5‐amino‐1‐benzyloxymethyl‐2,3

Reductive cleavage of permethylated polysaccharides with borane-methyl sulfide complex and butyltin trichloride

Several per- O-methylated monosaccharides and polysaccharides were used as models in an attempt to identify more convenient reagents for accomplishing reductive cleavage of glycosidic linkages. Included in the model studies were methyl α- and β- d-glucopyranoside, methyl α- and β- d-mannopyranoside, and methyl α- and β- d-ribofuranoside. These studies led to the identification of a new promoter, butyltin trichloride, for carrying out reductive cleavage when borane-methyl sulfide complex was used as the reducing agent. These reagents were found to accomplish the reductive cleavage of per- O-methylated amylose, cellulose, and pullulan to give only the expected derivatives of 1,5-anhydro- d-glucitol. These reagents also accomplished reductive cleavage of per- O-methylated inulin to give only the expected derivatives of 2,5-anhydro- d-mannitol and 2,5-anhydro- d-glucitol. Reductive cleavage using these reagents is easy to perform, and subsequent acetylation of the products is readily accomplished in situ. Mixtures of borane-methyl sulfide complex and boron trifluoride etherate were found to accomplish the reductive cleavage of several fully methylated methyl glycosides as well as fully methylated amylose, cellulose, pullulan, and inulin to given only the expected products.

ChemInform Abstract: A Facile Transformation of Benzylated Methyl Glycosides to Thioglycosides.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Mechanism of Ca2- and Monosaccharide Binding to a C-type Carbohydrate-recognition Domain of the Macrophage Mannose Receptor

Site-directed mutagenesis has been used to identify residues that ligate Ca2+ and sugar to the fourth C-type carbohydrate-recognition domain (CRD) of the macrophage mannose receptor. CRD-4 is the only one of the eight CRDs of the mannose receptor to exhibit detectable monosaccharide binding when expressed in isolation, and it is central to ligand binding by the receptor. CRD-4 requires two Ca2+ for sugar binding, like the CRD of rat serum mannose-binding protein (MBP-A). Sequence comparisons between the two CRDs suggest that the binding site for one Ca2+, which ligates directly to the bound sugar in MBP-A, is conserved in CRD-4 but that the auxiliary Ca2+ binding site is not. Mutation of the four residues at positions in CRD-4 equivalent to the auxiliary Ca2+ binding site in MBP-A indicates that only one, Asn728, is involved in ligation of Ca2+. Alanine-scanning mutagenesis was used to identify two other asparagine residues and one glutamic acid residue that are probably involved in ligation of the auxiliary Ca2+ to CRD-4. Sequence comparisons with other C-type CRDs suggest that the proposed binding site for the auxiliary Ca2+ in CRD-4 of the mannose receptor is unique. Evidence that the conserved Ca2+ in CRD-4 bridges between the protein and bound sugar in a manner analogous to MBP-A was obtained by mutation of one of the amino acid side chains at this site. Ring current shifts seen in the 1H NMR spectra of methyl glycosides of mannose, GlcNAc, and fucose in the presence of CRD-4 and site-directed mutagenesis indicate that a stacking interaction with Tyr729 is also involved in binding of sugars to CRD-4. This interaction contributes about 25% of the total free energy of binding to mannose. C-5 and C-6 of mannose interact with Tyr729, whereas C-2 of GlcNAc is closest to this residue, indicating that these two sugars bind to CRD-4 in opposite orientations. Sequence comparisons with other mannose/GlcNAc-specific C-type CRDs suggest that use of a stacking interaction in the binding of these sugars is probably unique to CRD-4 of the mannose receptor.

Esterification of methyl glycoside mixtures by lipase catalysis

The acylation of a mixture of methyl α-D-galacto-, methyl β-D-gluco- and methyl β-D-mannopyranosides by octanoic acid was catalysed by lipases from Candida antarctica, Pseudomonas cepacia, Candida rugosa OF or Mucor miehei in acetonitrile at 45°C. The methyl glycopyranosides had the same anomeric configuration as that of the softwood hemicellulose galactoglucomannan. C. rugosa OF lipase had almost no substrate specificity and P. cepacia lipase had a high substrate specificity for the esterification of methyl α-D-galactopyranoside.

A Convenient Method for the Preparation of Disaccharides by Transglycosylation of Methyl Glycosides

AbstractTransglycosylation of methyl glycosides with various glycosyl acceptors using a Sn(OTf)2–Me3SiCl promoter system in the presence of molecular sieves 5A afforded the corresponding glycosides. Several useful disaccharides are effectively prepared in good yields with moderate to good stereoselectivities.

Synthesis of acosamine and daunosamine from sugar σ-enelactones

Conjugate addition-rearrangement of N-benzylhydroxylamine to lactones 11 and 12 provided respective isoxazolidin-5-ones 13 and 14 which were in turn mesylated at the hydroxy group and subjected to the next skeleton rearrangement to afford N,3,4,5-tetrasubstituted isoxazolidines 18 and 19 in such a way that inversion of configuration at C-5 of the sugar chains occured. Standard transformation of isoxazolidines 18 and 19 provided methyl glycoside of N,O-diacetate of acosamine 33 and daunosamine 34, respectively.

New optically pure sugar hydroperoxides. Synhtesis and use for enantioselective oxygen transfer

2-Deoxy-2- C-methylene methyl glycosides undergo oxidation with hydrogen peroxide in the presence of molybdenum trioxide as catalyst to afford the corresponding anomeric hydroperoxides. These hydroperoxides were used as chiral oxidants of allylic alcohols and prochiral sulfides to offer moderate enantioselectivities which were, however, higher than those reported before oxidation with optically active peroxyacids.

Mechanism of anomerization of cyclohexyl 2-deoxy-3,4,6-tri- O-methyl-2-( N-methylacetamido)- α- and β- d-hexopyranosides under reductive-cleavage conditions

The fully methylated cyclohexyl glycosides of 2-acetamido-2-deoxy-α- and β- d-hexopyranoses having the gluco, manno, and galacto configurations were each subjected to reductive-cleavage conditions using one of three promoters, namely trimethylsilyl trifluoromethanesulfonate, a mixture of trimethylsilyl methanesulfonate and boron trifluoride etherate, or boron trifluoride etherate alone. As expected, the fully methylated 1,2-trans-linked acetamido sugar derivatives were rapidly converted to their respective oxazolinium ions with all three promoters. Surprisingly, however, the fully methylated 1,2-cis-linked acetamido sugar derivatives were also converted to their respective oxazolinium ions, albeit at a much slower rate. In the latter case, evidence was obtained for anomerization to the 1,2-trans-linked isomers under reductive-cleavage conditions. Since the anomerization was relatively slow at room temperature in dichloromethane, a modified procedure was developed in which the reaction was carried out at 70 °C in 1,2-dichloroethane. Using the modified procedure, all 1,2-cis- and 1,2-trans-linked acetamido sugar derivatives were rapidly converted into their respective oxazolinium ions and subsequent quenching of the reactions with anhydrous methanol gave the respective 1,2-trans-linked methyl glycoside derivatives in quantitative yield. The modified procedure is recommended for the total reductive cleavage of polysaccharides comprised of acetamido sugar residues.

Chemical Synthesis of (3-SO3Na)GlcNAcβ1→3Fucβ1→OMe: The Oligosaccharide Involved in the Cell Aggregation of the SpongeMicrociona Prolifera

ABSTRACT The methyl glycoside, (3-SO3Na)GlcNAcβ1→3Fucβ1→OMe, of a sulfated disaccharide that is involved in the species-specific reaggregation of dissociated cells of Microciona prolifera, was stereoselectively synthesized starting from L-fucose and 2-amino-2-deoxy-D-glucose.

Synthesis and conformational studies of the tyvelose capped, Lewis-x like tetrasaccharide epitope of Trichinella spiralis

Chemical synthesis and high resolution NMR studies are reported for the tetrasaccharide epitope and constituent structures that occur as terminal elements of Trichinella spiralis cell surface glycans. The 2-(trimethylsilyl)ethyl and methyl glycosides of Lewis-x type trisaccharides, in which βGalNAc replaces βGal were synthesized from monosaccharide synthons utilizing thioglycoside and halide-ion glycosylation methods. The unique 3,6-dideoxy-β- d-arabinohexopyranosyl residue that caps the structure was introduced to selectively protected 2-(trimethylsilyl)ethyl and methyl trisaccharide glycosides by utilizing an insoluble silver zeolite catalyst and a glycosyl halide. In separate reactions not only were the principal targets obtained but also the corresponding α-linked tetrasaccharides. A comparison of the NMR spectra of the methyl tetrasaccharide glycosides showed that at the site of the α-linked tyvelose structure, specific GalNAc resonances ( C-1, C-2, C-3) possess uncharacteristically wide 13C (8–21 Hz) and 1H lines. The β-linked tetrasaccharide glycoside, that represents the native parasite epitope, exhibited only narrow line widths (3 Hz, 13C). Since NOE derived distance constraints for the α-linked tyvelose structure were not consistent with the existence of unusual glycosidic conformers, the origin of the limited number of wide lines was attributed to local rigidity in the GalNAc residue, at the site of tyvelose glycosylation.

Liquid secondary ion mass spectrometry of methyl glycosides of oligosaccharides using matrices containing carboxamides.

Intense cluster ions corresponding to proton-bound hetero-dimers of an amide molecule and an oligosaccharide molecule are observed in the liquid secondary ion mass spectra of methyl glycosides of oligoxylans if a solution of an aliphatic carboxamide in glycerol is used as the liquid matrix. These cluster ions are particularly abundant and persist for a long period if urea (U) or thiourea (TU) is used as the matrix additive. In these cases, cluster ions containing more than one molecule of U or TU and two oligosaccharide molecules are also observed. The intense signal due to the proton-bound hetero-dimer between U or TU and the oligosaccharide can be used with advantage for a molecular weight determination. The bonding interactions between a protonated saccharide molecule and a molecule U or TU in the proton-bound hetero-dimers are so strong that the urea molecules remain attached to the fragment ions during the decay of metastable cluster ions and even during collision-induced dissociation. Thus, the mass-analysed ion kinetic energy spectra of these proton-bound hetero-dimers are dominated by abundant cluster ions [Bn+U] and [Ym+U] arising from cleavage of the glycosidic bonds within the oligosaccharides. The collisionally-activated mass spectra of the proton-bound hetero-dimers additionally contain peaks of the free ions Bn and Ym. Therefore, these spectra clearly reflect the arrangement of the monosaccharide residues in the oligosaccharide and can be used conveniently for structural analysis.