Hans Lönn

Thioglycosides as glycosylating agents in oligosaccharide synthesis

A review is given of the use of thioglycosides as glycosyl donors in oligosaccharide synthesis. Both indirect use, by conversion of the thioglycoside into a glycosyl halide and direct use, by electrophilic activation of the thioglycoside, are discussed.

Exceptionally high yield in glycosylation with sialic acid. Synthesis of a GM3 glycoside.

Abstract Exceptionally high yield was obtained in the glycosylation of HO-3 of lactose derivative 1 with xanthate 2 as sialosyl donor using methylsulfenyl triflate in acetonitrile/dichloromethane at −60°C. The yield of the sialosyl oligosaccharide was dependent on the amount of sialosyl donor used. The yields were 63, 75 and 82% using 1.1, 1.68 and 2.0 equivalents respectively of donor and 1.0 equivalent of acceptor.

New derivatization and separation procedures for reducing oligosaccharides

Abstract4-Trifluoroacetamidoaniline was reacted with reducing oligosaccharides in the presence of sodium cyanoborohydride to give aminoalditol derivatives, useful for linkage to proteins or solid matrices. A mixture of reducing oligosaccharides, difficult to separate by HPLC, was treated in the same way. The resulting derivatives were easily separated by HPLC.

Synthesis of Galβ1-3GlcNAc and Galβ1-3GlcNAcβ-SEt by an enzymatic method comprising the sequential use of β-galactosidases from bovine testes andEscherichia coli

Galβ1-3GlcNAc (1) and Galβ1-3GlcNAcβ-SEt (2) were synthesized on a 100 mg scale by the transgalactosylation reaction of bovine testes β-galactosidase with lactose as donor andN-acetylglucosamine and GlcNAcβ-SEt as acceptors. In both cases the product mixtures contained unwanted isomers and were treated with β-galactosidase fromEscherichia coli which has a different specificity, under conditions favouring hydrolysis, yielding besides the desired products, monosaccharides and traces of trisaccharides. The products were purified to >95% by gel filtration, with a final yield of 12% of 1 and 17% of 2, based on added acceptor. In a separate experiment Galβ1-6GlcNAcβ-SEt (3) was synthesized by the transglycosylation reaction using β-galactosidase fromEscherichia coli. No other isomers were detected. Compound 3 was purified by HPLC.

Synthesis of an H type 2 and a Y (Ley) glycoside from thioglycoside intermediates

The trisaccharide 2-(p-trifluoroacetamidophenyl)ethyl 2-acetamido-2-deoxy-4-O-[2-O-(α-l-fucopyranosyl)-β-d-galactopyranosyl]-β-d-glucopyranoside 1 and the tetrasaccharide 2-(p-trifluoroacetamidophenyl)ethyl 2-acetamido-2-deoxy-3-O-(α-l-fucopyranosyl)-4-O-[2-O-(α-l-fucopyranosyl)-β-d-galactopyranosyl]-β-d-glucopyranoside 2 were synthesized. Thioglycosides, suitably protected, activated directly with methyl trifluoromethanesulfonate or dimethyl(methylthio)sulfonium tetrafluoroborate or activated after bromine treatment with halophilic reagents, were used as glycosyl donors in the construction of the glycosidic linkages.

Convergent synthesis of neoglycopeptides by coupling of 2-bromoethyl glycosides to cysteine and homocysteine residues in T cell stimulating peptides

The 2-bromoethyl β-glycosides of the disaccharide galabiose [Gal(α1-4)Gal] and the trisaccharides globotriose [Gal(α1-4)Gal(β1-4)Glc] and 3′-sialyllactose [Neu5Ac(α2-3)Gal(β1-4)Glc] have been prepared by improved routes. The 2-bromoethyl glycosides were then used in cesium carbonate promoted alkylations of the sulfhydryl groups of cysteine and homocysteine residues in T cell stimulating peptides. This convergent and general approach was used to prepare 16 neoglycopeptides which were obtained in 52–95% yields after purification by HPLC. 1H NMR spectroscopy revealed that β-elimination and epimerization of neoglycopeptide stereocentres did not occur during the synthesis.

Derivatization procedures for reducing oligosaccharides, part 2: Chemical transformation of 1-deoxy-1-(4-trifluoroacetamidophenyl)aminoalditols

Three chemical transformations of oligosaccharide 1-deoxy-1-(4-trifluoroacetamidophenyl)aminoalditols are described. 1) Oxidation with hydrogen peroxide to give the corresponding reducing oligosaccharides. 2) Oxidation with cerium ammonium nitrate to give the corresponding 1-amino-1-deoxyalditols. 3) Treatment with acetic anhydride to give the correspondingN-acetylated derivatives, which are more stable towards oxidation.

Sulfurylchloride/trifluoromethanesulfonic acid. A novel promoter system for glycoside synthesis using thioglycosides as glycosyl donors

The use of thioglycosides as glycosyl donors in oligosaccharide synthesis has been reviewed [1]. This communication reports a novel method of activation of 1-thioglycosides using sulfuryl chloride in the presence of trifluoromethanesulfonic acid. The reaction of sulfuryl chloride with sulfides in the presence of a stro~lg acid is known to produce a chlorosulfonium salt ~2], and it was reasoned that this reaction could be useful in glycoside synthesis using thioglycosides of glycosy[ donors. Preliminary results have indicated this to be the case.

Synthetic mucin fragments: 2-(p-trifluoroacetamidophenyl) ethyl 2-acetamido-6-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-2-deoxy-3-O-(β-d-galactopyranosyl)-α-d-galactopyranoside and 2-(p-trifluoroacetamidophenyl) ethyl 2-acetamido-6-O-[2-acetamido-2-deoxy-4-O-(β-d-galactopyranosyl)-β-d-glucopyranosyl]-2-deoxy-3-O-(β-d-galactopyranosyl)-α-d-galactopyranoside

The title compounds were synthesized from methyl 2-azido-3-O-(2,3,4,6-tetra-O-benzoyl-β-d-galactopyranosyl)-2-deoxy-1-thio-β-d-galactopyranoside, which was β-glycosylated in the 6-position with glucosamine or lactosamine derivatives.The tri- and tetrasaccharide thioglycosides obtained were then converted to the 2-(p-trifluoroacetamidophenyl) ethyl α-glycosides and deprotected.

Glycosidations with thioglycosides activated by sulfuryl chloride/trifluoromethanesulfonic acid: synthesis of a human blood group B trisaccharide glycoside

The trisaccharide 2-(p-trifluoroacetamidophenyl)ethyl 2-O-(α-l-fucopyranosyl)-3-O-(α-d-galactopyranosyl)-β-d-galactopyranoside, corresponding to the human blood group B determinant, was synthesized. Thioglycosides activated by sulfuryl chloride/trifluoromethanesulfonic acid were used as glycosyl donors in the construction of the three glycosidic linkages.