Lóránt Jánossy

Synthesis of chromogenic substrates of α-amylases on a cyclodextrin basis

Abstract One-pot acetylation and subsequent partial acetolysis of α-, β- and γ-cyclodextrins resulted in crystalline peracetylated malto-hexaose, -heptaose, and -octaose, respectively. Prolonged acetolysis of β-cyclodextrin gave a mixture of acetylated maltooligosaccharides, from which peracetylated malto-triose, -tetraose, and -pentaose were isolated. The acetylated oligosaccharides were converted into α-acetobromo derivatives, and then transformed into 4-nitrophenyl and 2-chloro-4-nitrophenyl β-glycosides. From the 4-nitrophenyl glycosides 4,6-O-benzylidene derivatives were prepared, which were used together with the free glycosides as substrates of porcine pancreatic α-amylase. One-pot acetylation and subsequent partial acetolysis of cyclodextrins resulted in the peracetylated maltooligomers (dp 3–8), which were transformed into 4-nitrophenyl and 2-chloro-4-nitrophenyl β-glycosides, the 4.6-O-benzylidene derivatives of NP-glycosides were also prepared

Preparation of (2-naphthyl)methylene acetals of glycosides and their hydrogenolytic transformation into 2-naphthylmethyl (NAP) ethers

Abstract Dioxane- and dioxolane-type (2-naphthyl)methylene acetals of glycosides were prepared by acid-catalyzed transacetalization reactions. The acetals were cleaved using either AlH3 (LiAlH4:AlCl3=3:1), NaCNBH3–HCl or BH3 Me3N–AlCl3 reagents. Reaction of the 4,6-O-acetals with AlH3 yielded 4-ONAP ethers whereas the other two reagents gave 6-ONAP derivatives with excellent regioselectivity. In dioxolane-type acetals the direction of the cleavage with all three reagents is determined by the stereochemistry of the acetal center; equatorial ONAP/axial-hydroxy derivatives are obtained from the exo-naphthyl isomers; endo-naphthyl acetals, on the other hand, give rise to the formation of axial ONAP/equatorial-hydroxy compounds. The NAP ether and the (2-naphthyl)methylene acetal protecting groups can both be readily removed by treatment with DDQ.

Synthesis of the α-L-Araf-(1 → 2)-β-D-Galp-(1 → 6)-β-D-Galp-(1 → 6)-[α-L-Araf-(1 → 2)]-β-D-Galp-(1 → 6)-D-Gal hexasaccharide as a possible repeating unit of the cell-cultured exudates of Echinacea purpurea arabinogalactan

Abstract For the characterization of the supposed epitope of an arabinogalactan, isolated from the extract of the cell-cultured Echinacea purpurea, the title hexasaccharide was synthesized. The whole synthetic route was based on the 6-O-(methoxydimethyl)methyl ether (MIP) protecting group strategy. 2-O-Benzyl-3,4-O-isopropylidene-6-O-(methoxydimethyl)methyl-β- d -galactopyranosyl-(1→6)-1,2:3,4-di-O-isopropylidene-α- d -galactopyranose was used to prepare the desired glycosyl donor and glycosyl acceptor both carrying a persistent O-benzyl group at position 2′. Reaction of the digalactose donor and the digalactose acceptor resulted in a β-(1→6)-linked galactose-containing tetrasaccharide in which OH-2′ and OH-2′′′ were substituted with benzyl groups. Hydrogenolytic removal of the benzyl groups of the tetragalactose compound gave the diol aglycon which was diarabinosylated in one step to furnish the protected target compound, whose deprotection led to the title hexasaccharide. All of the synthesized compounds were characterized by 1H and 13C NMR spectra, as well as by MALDI-TOF mass-spectrometry measurements.

Synthesis of an arabinogalactan-type octa- and two isomeric nonasaccharides. Suitable tuning of protecting groups

Abstract An arabinogalactan-type double-branched octa- and two isomeric nonasaccharides were synthesized using the (2-naphthyl)methyl (NAP) and the acid sensitive but base stable (methoxydimethyl)methyl (MIP) protecting groups. The β-(1→6)-linked hexagalactan skeleton was synthesized having a benzyl and a (2-naphthyl)methyl (NAP) group at positions 2 of the second and the penultimate galactopyranosyl units, and this made possible sequential introduction of α- l -arabinofuranosyl or α- l -arabinofuranosyl-(1→5)-α- l -arabinofuranosyl side chains.

Scope and limitation of the application of the (methoxydimethyl)methyl group in the synthesis of 2′-O-, 6′-O- and 2′,6′-di-O-(α-l-arabinofuranosyl)-β-d-galactopyranosyl-(1→6)-d-galactoses

Abstract For the characterisation of the anticipated epitope of an arabinogalactan, isolated from the extract of Echinacea purpurea, the trisaccharide α- l -Ara f -(1→2)-β- d -Gal p -(1→6)- d -Gal was synthesized. The easily available 3,4- O -isopropylidene-6- O -(methoxydimethyl)methyl-β- d -galactopyranosyl-(1→6)-1,2:3,4-di- O -isopropylidene-α- d -galactopyranose having the OH-2′ free served as aglycone upon direct arabinosylation at the 2′ position under Helferich conditions. The formed HgBr 2 cleaved the acid sensitive protecting group at position 6′, but under basic conditions the desired, fully protected trisaccharide, or its symmetrical dimerization derivative linked 6′- to 6′-position via an isopropylidene bridge, could be obtained. An alternative route involved arabinosylation of a hepta-O-acetylated digalactose with free OH-2′. Two other oligosaccharides, namely, α- l -Ara f -(1→6)-β- d -Gal p -(1→6)- d -Gal and (α- l -Ara f ) 2 -(1→2,6)-β- d -Gal p -(1→6)- d -Gal were also synthesized and characterised.

Modeling and biochemical analysis of the activity of antibiofilm agent Dispersin B

Bacteria in a biofilm are enmeshed in a self-synthesized extracellular polysaccharide matrix (PGA), which is a linear polymer of beta(1,6)-linked N-acetylglucosamine (GlcNAc) residues. Dispersin B (DspB), a soluble glycoside hydrolase produced by the periodontal pathogen Actinobacillus actinomycetemcomitans degrades PGA. The enzyme DspB is an alpha/beta TIM-barrel protein and belongs to family 20 glycosyl hydrolases members. The enzyme activity of DspB with regard to its substrate specificity towards beta(1,6)-linked GlcNAc polymers and its endo/exo character was investigated through ligand docking and the hydrolysis of synthetic oligosaccharides. Ligand docking analysis suggested that beta(1,6)-linked GlcNAc oligosaccharide bound to the active site better that beta(1,4)-linked GlcNAc oligosaccharide. Our combined results indicate that DspB is an exo-acting enzyme that hydrolyzes beta(1,6)-linked N-acetylglucosamine oligomers.

Mixed acetals of cyclodextrins. Preparation of hexakis-, heptakis- and octakis[2,6-di-O-(methoxydimethyl)methyl]-α-, β- and γ-cyclodextrins

Abstract The proton-catalyzed addition of 2-methoxypropene to α-, β- and γ-cyclodextrins resulted in hexakis-, heptakis-, and octakis[2,6-di -O- (methoxydimethyl)methyl]-α-, β- and γ-cyclodextrins, but no reaction was observed of CD-s with 2,2-dimethoxypropane. The mixed acetal-type compounds can be alkylated under basic conditions. The preparation of hexakis(3 -O- benzyl)-α-cyclodextrin demonstrates the synthetic value of this methodology.

Synthesis and Semisynthesis of Some Structural Elements of Oligo-Mannose Type N-Glycoproteins

Abstract For the construction of N-glycoprotein glycan chains, valuable potential glycosyl donors, O-α-D-mannopyranosyl-(1→2)-α-D-mannopyranose octaacetate (19) and O-α-D-mannopyranosyl-(1→2)-O-α-D-mannopyranosyl-(1→2)-α-D-mannopyranose undeca-acetate (20) were obtained in gram-scale by the acetylation and subsequent partial acetolysis of bakers yeast, without the isolation of mannan. The acetolytic products were investigated by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Octaacetates of mannobiose (1→3) (11) and (1→6) (17) were chemically synthesized.