Sialic Acid Glycosides Research Articles

ChemInform Abstract: The Isothiocyanato Moiety: An Ideal Protecting Group for the Stereoselective Synthesis of Sialic Acid Glycosides and Subsequent Diversification.

The preparation of a crystalline, peracetyl adamantanyl thiosialoside donor protected by an isothiocyanate group is described. On activation at -78 C in the presence of typical carbohydrate acceptors this donor gives high yields of the corresponding sialosides with exquisite α-selectivity. The high selectivity extends to the 4-O-benzyl-protected 3-OH acceptors that are typically less reactive and selective than galactose 3,4-diols. Treatment of the α-sialosides with tris(trimethylsilyl)silane or allyltris(trimethylsilyl)silane sialosides replaces the C5-N5 bond by a C-H or a C-C bond. Reaction of the isothiocyanate-protected sialosides with thioacids achieves conversion into amides. Reaction of the isothiocyanate with an amine gives a thiourea, which can be converted to a guanidine. The very high α-selectivities observed with the new donor and the rich chemistry of the isothiocyante function considerably extend the scope for optimization at the sialoside 5-position.

The Isothiocyanato Moiety: An Ideal Protecting Group for the Stereoselective Synthesis of Sialic Acid Glycosides and Subsequent Diversification

AbstractThe preparation of a crystalline, peracetyl adamantanyl thiosialoside donor protected by an isothiocyanate group is described. On activation at −78 °C in the presence of typical carbohydrate acceptors, this donor gives high yields of the corresponding sialosides with exquisite α‐selectivity. The high selectivity extends to the 4‐O‐benzyl‐protected 3‐OH acceptors, which are typically less reactive and selective than galactose 3,4‐diols. Treatment of the α‐sialosides with tris(trimethylsilyl)silane or allyltris(trimethylsilyl)silane results in replacement of the C5N5 bond by a CH or a CC bond. The reaction of the isothiocyanate‐protected sialosides with thioacids generates amides, while reaction with an amine gives a thiourea, which can be converted into a guanidine. The very high α‐selectivities observed with the new donor and the rich chemistry of the isothiocyante function considerably extend the scope for optimization at the sialoside 5‐position.

The isothiocyanato moiety: an ideal protecting group for the stereoselective synthesis of sialic acid glycosides and subsequent diversification.

The preparation of a crystalline, peracetyl adamantanyl thiosialoside donor protected by an isothiocyanate group is described. On activation at -78 °C in the presence of typical carbohydrate acceptors, this donor gives high yields of the corresponding sialosides with exquisite α-selectivity. The high selectivity extends to the 4-O-benzyl-protected 3-OH acceptors, which are typically less reactive and selective than galactose 3,4-diols. Treatment of the α-sialosides with tris(trimethylsilyl)silane or allyltris(trimethylsilyl)silane results in replacement of the C5-N5 bond by a C-H or a C-C bond. The reaction of the isothiocyanate-protected sialosides with thioacids generates amides, while reaction with an amine gives a thiourea, which can be converted into a guanidine. The very high α-selectivities observed with the new donor and the rich chemistry of the isothiocyante function considerably extend the scope for optimization at the sialoside 5-position.

Probing the influence of protecting groups on the anomeric equilibrium in sialic acid glycosides with the persistent radical effect.

A method for the investigation of the influence of protecting groups on the anomeric equilibrium in the sialic acid glycosides has been developed on the basis of the equilibration of O-sialyl hydroxylamines by reversible homolytic scission of the glycosidic bond following the dictates of the Fischer–Ingold persistent radical effect. It is found that a trans-fused 4O,5N-oxazolidinone group stabilizes the equatorial glycoside, i.e., reduces the anomeric effect, when compared to the 4O,5N-diacetyl protected systems. This effect is discussed in terms of the powerful electron-withdrawing nature of the oxazolidinone system, which in turn is a function of its strong dipole moment in the mean plane of the pyranose ring system. The new equilibration method displays a small solvent effect and is most pronounced in less polar media consistent with the anomeric effect in general. The unusual (for anomeric radicals) poor kinetic selectivity of anomeric sialyl radicals is discussed in terms of the planar π-type structure of these radicals and of competing 1,3-diaxial interactions in the diastereomeric transition states for trapping on the α- and β-faces of the radical.

Influence of side chain conformation and configuration on glycosyl donor reactivity and selectivity as illustrated by sialic acid donors epimeric at the 7-position.

Two N-acetyl 4O,5N-oxazolidinone-protected sialyl thioglycosides epimeric at the 7-position have been synthesized and their reactivity and stereoselectivity in glycosylation reactions have been compared. It is demonstrated that the natural 7S-donor is both more reactive and more α-selective than the unnatural 7R-isomer. The difference in reactivity is attributed to the side chain conformation and specifically to the proximity of O7 to the anomeric center. In the natural 7S-isomer, O7 is closer to the anomeric center than in its unnatural 7R-epimer and, therefore, better able to support incipient positive charge at the locus of reaction. The difference in selectivity is also attributed to the side conformation, which in the unnatural 7R-series is placed perpendicularly above the α-face of the donor and so shields it to a greater extent than in the 7S-series. These observations are consistent with earlier conclusions on the influence of the side chain conformation on reactivity and selectivity derived from conformationally locked models in the glucose and galactose series and corroborate the suggestion that those effects are predominantly stereoelectronic rather than torsional. The possible relevance of side chain conformation as a factor in the influence of glycosylation stereoselectivity by remote protecting groups and as a control element in enzymic processes for glycosidic bond formation and hydrolysis are discussed. Methods for assignment of the anomeric configuration in the sialic acid glycosides are critically surveyed.

Chemical Diversification of Sialic Acid Glycosides by Stereospecific, Chemoselective Deamination

Late bloomer: Nitrosation of peracetylated sialic acid glycosides followed by treatment with sodium trifluoroethoxide and then a suitable nucleophile enables the late-stage modification of these glycosides with stereospecific replacement of the acetamido group. This method should enable access to many glycoside derivatives with a minimum of synthetic effort.

Chemical Diversification of Sialic Acid Glycosides by Stereospecific, Chemoselective Deamination

Chemical Diversification of Sialic Acid Glycosides by Stereospecific, Chemoselective Deamination

Exploration of the Oxazolidinthione Protecting System for the Synthesis of Sialic Acid Glycosides

An N-acetyl oxazolidinthione-protected sialyl thioglycoside was synthesized and its use as a sialyl donor studied. The strongly electron-withdrawing nature of the oxazolidinthione moiety is such that activation could not be achieved at −78°C. Couplings were therefore conducted at the lowest convenient temperature (−50°C). Glycosides were formed in good yield but in two out of three cases studied selectivities were lower than those seen with the corresponding N-acetyl oxazolidinone-protected donor. The resulting N-acetyl oxazolidinthione-protected disaccharides were converted to the corresponding N-acetyl oxazolidinones by treatment with N-iodosuccinimide and triflic acid in the presence of water at 0°C.

Efficient glycosidation of a phenyl thiosialoside donor with diphenyl sulfoxide and triflic anhydride in dichloromethane.

The formation of sialic acid glycosides with a thiosialic acid derivative, diphenyl sulfoxide, and trifluoromethanesulfonic anhydride is reported. With an excess of diphenyl sulfoxide, glycal formation can be completely suppressed and excellent yields are obtained for coupling to a wide range of primary, secondary, and tertiary acceptors.

Recent Developments in Technology for Glycosylation with Sialic Acid.

AbstractFor Abstract see ChemInform Abstract in Full Text.

RECENT DEVELOPMENTS IN TECHNOLOGY FOR GLYCOSYLATION WITH SIALIC ACID

Sialic acids are a class of nine-carbon monosaccharides found at the termini of oligosaccharides in many mammalian cellular systems [1]. This class is represented by the prototypical congener N-acetylneuraminic acid (NeuAc, 1, Scheme 1). These unique sugars are ubiquitous, and they are present as components of both glycolipids and glycoproteins. Some examples of sialic acid containing oligosaccharides are shown in Scheme 2. Sialic acids are found in variety of glycosidic linkages, some more common of which are α-2,3or α-2,6-linkages to galactose residues. Additionally, they frequently exist as α-2,8-linked oligomers or polymers. The lack of efficient technology to accomplish glycosylations with sialic acid is one of the long-standing deficiencies in carbohydrate chemistry [2]. Owing to the central role of sialic acids in carbohydrate recognition events, the development of high-yielding and operable methods to synthesize sialic acid glycosides has been the subject of considerable research. The development of such methods allows the construction of complex sialic acid containing glycoconjugates for the investigation of their roles in biochemical and cellular processes. Most classical methods for synthesizing sialic acid glycosides are based on the reaction of an activated sialic acid such as 2 with an oligosaccharide glycosyl acceptor bearing a hydroxyl group nucleophile (Scheme 3) [2]. The leaving group is typically a halogen, such as a chloride or bromide, and the activator is typically a heavy metal salt [3,4]. A regioselective union of the two reacting partners of course relies on appropriate protecting group patterns for both the glycosyl donor and acceptor components. Many of the early methods are generally plagued with side reactions, low yields, and poor stereoselectivity. There are several reasons for

Synthesis of 4-Hydroxy-2,6-bis(hydroxymethyl)tetrahydropyran-2-carbaldehyde Derivatives

Cycloaddition of 1,3-dibromo-2-oxyallyl cation to 2-(benzyloxymethyl)furan provided a 8-oxabicyclo[3.2.1]hept-6-en-3-one derivative that was transformed into (2RS,3SR,4SR,5SR,6SR)-3,4-dibromo-2-benzyloxymethyl-2,6-bis(hydroxymethyl)-4-(methoxymethyloxy)tetrahydropyran. Selective protection and oxidation produced a protected 3,5-dibromo-4-hydroxy-2,6-bis(hydroxymethyl)tetrahydropyran-2-carbaldehyde that could be used to carry out cross-aldolisations, opening an approach to the synthesis of C-disaccharide analogues mimicking sialic acid glycosides.

5527901 Sialic acid glycosides, antigens, immunoadsorbents, and methods for their preparation : Ratcliffe Robert M; Venot Andre P; Abbas S Zahee Carlsbad, CA, United States assigned to Alberta Research Council

5527901 Sialic acid glycosides, antigens, immunoadsorbents, and methods for their preparation : Ratcliffe Robert M; Venot Andre P; Abbas S Zahee Carlsbad, CA, United States assigned to Alberta Research Council

Recognition of monovalent sialosides by influenza virus H3 hemagglutinin

This report presents a procedure for evaluating the relative affinities of simple sialoside receptor determinants for their interaction with the receptor binding pocket of the influenza virus hemagglutinin. The virus examined was A/Memphis/102/72, previously shown to exhibit preferential binding specificity for enzymatically modified erythrocytes containing the NeuAcα2,6GaI linkage. Sialosides examined included those with structures representative of terminal sequences found on carbohydrate groups of naturally occurring glycoproteins and glycolipids. Sialosides with the NeuAcα2,6GaI and NeuAcα2,6GIcNAc linkage were 5–30 times more potent inhibitors than those with the NeuAcα2,3Gal linkage. The results provide evidence that the previously reported specificity of the A/Memphis/102/72 hemagglutinin for the NeuAcα2,6Gal sequence on cell surface receptors was due to differential affinity of the receptor binding pocket for sialoside sequences, apart from contributions due to the protein or lipid portions of the cell surface receptors. A number of synthetic sialic acid glycosides were also evaluated as inhibitors of viral attachment. The differential inhibition observed with these receptor analogs may provide clues to the detailed molecular interaction of sialosides with the hemagglutinin binding pocket and aid in the design of small molecular weight inhibitors of viral adsorption to cells.

The Sialic Acids: XI. A PERIODATE-RESORCINOL METHOD FOR THE QUANTITATIVE ESTIMATION OF FREE SIALIC ACIDS AND THEIR GLYCOSIDES

The Svennerholm resorcinol method for the quantitative determination of the sialic acids was modified by introducing a periodate oxidation step prior to heating with the resorcinol reagent. Sialic acid glycosides could be determined without acid hydrolysis. The glycosides gave chromogens stable to periodate oxidation at 37°, whereas free sialic acid gave chromogens that were destroyed at this temperature, but were stable at 0°. Using these properties, the periodate-resorcinol method was applied to the determination of total, free, or bound sialic acid. The periodate-resorcinol method was substantially more sensitive than the resorcinol procedure, was not affected by lipids, amino acids, or sugars, and could be used to detect free or glycosidically bound sialic acids on paper chromatograms.

The Sialic Acids: IX. ISOLATION OF CYTIDINE 5'-MONOPHOSPHO-N-ACETYLNEURAMINIC ACID FROM ESCHERICHIA COLI K-235

A novel type of sugar nucleotide, containing 1 rather than 2 phosphate residues, was isolated from Escherichia coli K-235. The nucleotide was shown to be cytidine 5'-monophospho-N-acetylneuraminic acid in which the sialic acid was glycosidically linked to the phosphate residue. The glycoside was highly sensitive to acid, and optical rotation studies showed that it was the β anomer, in contrast to other known, natural, sialidase-sensitive sialic acid glycosides.