François D. Tropper

STEREOSELECTIVE PHASE TRANSFER CATALYZED SYNTHESES OF GLYCOSYLOXYSUCCINIMIDES AND THEIR TRANSFORMATIONS INTO GLYCOPROBES

Abstract Glycosyloxysuccinimides of D-galactose, D-glucose, N-acetyl-D-glucosamine, lactose, maltose (7–11) and sialic acid (13) were prepared from their glycosyl halides under PTC conditions. Ring opening of the succinimide moieties occurred with sodium hydroxide or methoxide to provide extended aglycons, while treatment of 8 with hydrazine afforded O-galactopyranosylhydroxylamine 17. Treatment of 9 with tris(2-aminoethyl)amine gave divalent cluster 20 which upon further treatment with fluorescein isothiocyanate provided divalent glycoprobe 21.

Stereospecific Synthesis of Aryl β-D-N-Acetylglucopyranosides by Phase Transfer Catalysis

Abstract Under phase transfer catalyzed conditions, 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-glucopyranosyl chloride (1) reacts with a series of phenoxides to afford high yields of acetylated aryl β-D-N-acetylgluco-pyranosides (3–8). Deprotection of the hydroxyl groups under Zemplen condition gave quantitative yields of the free glycosides 3a-8a.

Syntheses of copolymer antigens containing 2-acetamido-2-deoxy-α- orβ-d-glucopyranosides

The synthesis of artificial carbohydrate antigens derived from allyl 2-acetamido-2-deoxy-α-and β-d-glucopyranosides and acrylamide is described. The two anomeric glycosyl copolymers were prepared with and without spacer arms and their binding properties to lectins and antibodies are compared.

Expedient syntheses of neoglycoproteins using phase transfer catalysis and reductive amination as key reactions

Starting from peracetylated chloro- or bromo-glycosyl donors ofN-acetylneurmainic acid,N-acetylglucosamine, glucose and lactose, the correspondingp-formylphenyl glycosides were synthesized stereospecifically under phase transfer catalysed conditions at room temperature in yields of 38–67%. After Zemplén de-O-acetylation, the formyl groups were directly and chemoselectively coupled to the lysine residues of bovine serum albumin by reductive amination using sodium cyanoborohydride. The conjugation reactions were followed as a function of time and under a series of different molar ratios of the reactants to provide glycoconjugates of varying degree of antigenicities. Thus, carbohydrate protein conjugates were made readily available using essentially two key reactions.

Phase transfer catalysis toward the synthesis of O-, S-, Se- and C-glycosides

Phase transfer catalysis (PTC) has been used for the synthesis of anomeric glycosyl derivatives, which included O-, S-, Se- and C- glycosides. These various glycosyl derivatives have been stereospecifically obtained from glycosyl halides 1, 2, 3, 14, 26. These reactions proceeded in generally good yields, and were essentially complete within 3 h.

Synthesis of antigenic carbohydrate polymers recognized by lectins and antibodies

The alkene group of allyl α-L-rhamnopyranoside has been converted to an N-acryloyl spacer arm which was copolymerized with acrylamide to afford water soluble carbohydrate copolymers; these have antigenic properties demonstrated by their binding to Ricinus communis lectin and to the antisera to the capsular polysaccharide of Streptococcus pneumoniae type 23.

Michael addition of poly-L-lysine to N-acryloylated sialosides. Syntheses of influenza A virus haemagglutinin inhibitor and group B meningococcal polysaccharide vaccinest

N-Acryloylated sialoside derivatives are directly conjugated to poly-L-lysine and protein carriers by the 1,4-conjugate additions of their NIµ-lysine residues to provide new glycoconjugates with potential therapeutic utilities.

Syntheses and transformations of glycohydrolase substrates into protein conjugates based on Michael additions

The glycosyl chloride 1 and bromides 2 and 3 were stereospecifically transformed into p-nitrophenyl glycosides by phase transfer catalysis; these glycohydrolase substrates were reduced and N-acryloylated to afford Michael acceptors which reacted with amine functions of proteins.

Custom-designed glycopolymer syntheses by terpolymerizations

Carbohydrate derivatives having lectin binding properties and bearing N-acryloyl functionality have been copolymerized under three-component terpolymerization conditions with acrylamide and N-acryloylated effector molecules to provide water-soluble glycopolymers with custom designed physico-chemical properties.

Direct access to neoglycoproteins and glycopolymers from single precursors. Synthesis of T-antigen and N-acetyl-lactosamine-β-D-(1→6)-α-D-GalNAc conjugates

Abstract Michael addition and acrylamide copolymerization of single N-acryloylated carbohydrate precursors of the Thomsen Friedenreich antigen (T-antigen) and an ABH type 2 human blood group trisaccharide determinant afforded both neoglycoprotein and glycopolymer conjugates suitable for immunochemical studies.