A new method testing the orthogonality of different protecting groups.

A new test was elaborated to identify a new set of orthogonal protecting groups. With the developed method eight different protecting groups were tested under various deprotection conditions and the complex reaction mixtures were analysed by HPLC. The developed method allows for quick identification of orthogonality using simple model structures.

Preparation of new type of organocatalysts having a carbohydrate scaffold.

The synthesis of nine new, bifunctional organocatalysts having carbohydrate scaffolds has been accomplished. In these catalysts both of the catalytic amino and thiourea functions are directly attached to a carbohydrate core. The activities of the newly prepared catalysts were tested in a Michael addition.

Assessing toxicity of polyamidoamine dendrimers by neuronal signaling functions.

We report for the first time on neuronal signaling for the evaluation of interactions between native plasmamembrane and polyamidoamine (PAMAM) dendrimers. Generation 5 polycationic (G5-NH(2)), novel ß-D-glucopyranose-conjugated G5-NH(2) and generation 4.5 polyanionic (G4.5-COONa) polyamidoamine (PAMAM) dendrimers (1-0.0001 mg/ml) were applied in acute brain slices. Functional toxicity assessments-validated by fluorescence imaging of dead cells-were performed by employing electrophysiological indicators of plasma membrane breakdown and synaptic transmission relapse. Irreversible membrane depolarization and decrease of membrane resistance predicted substantial functional neurotoxicity of unmodified G5-NH(2), but not of the G4.5-COONa PAMAM dendrimers. Model calculations suggested that freely moving protonated NH(2) groups of terminal monomeric units of PAMAM dendrimers may be able directly destroy the membrane or inhibit important K(+) channel function via contacting the positively charged NH(2). In accordance, conjugation of surface amino groups by ß-D-glucopyranose units reduced functional neurotoxicity that may hold great potential for biomedical applications.

Some observations on the reductive ring opening of 4,6-O-benzylidene acetals of hexopyranosides with the borane trimethylamine-aluminium chloride reagent.

Reductive ring openings of 3-O-benzoyl-4,6-O-benzylidene-D-glucopyranosides with BH(3)·NMe(3)-AlCl(3) are accompanied by side reactions, such as debenzoylation and reduction of the benzoate to benzyl ether. This phenomenon was rationalized by aluminium chelate formation between the O-4 acetal and the benzoyl carbonyl group oxygens. It was also shown that these side reactions can be eliminated by using BH(3)·THF as the reducing agent.

(2-Nitrophenyl)acetyl: a new, selectively removable hydroxyl protecting group.

The utility of the (2-nitrophenyl)acetyl (NPAc) group for the protection of hydroxyl functions is reported. (2-Nitrophenyl)acetates are readily prepared starting from the commercially available, inexpensive (2-nitrophenyl)acetic acid, and these esters are stable under a series of common carbohydrate transformations. The NPAc group can be removed selectively using Zn and NH(4)Cl without affecting a series of common protecting groups. This new protecting group is orthogonal with the commonly used tert-butyldimethylsilyl, levulinoyl, 9-fluorenylmethoxycarbonyl, naphthylmethyl, and p-methoxybenzyl groups.

An efficient synthesis of L-idose and L-iduronic acid thioglycosides and their use for the synthesis of heparin oligosaccharides.

Efficient preparations of thioglycoside derivatives of L-idose and L-iduronic acid are described. The method avoids the tedious chromatographic separations of furanose and pyranose anomeric mixtures, and affords the thioglycosides in a stereoselective manner. The L-idose and L-iduronic acid thioglycosides having combinations of different protecting groups proved to be efficient glycosyl donors in the synthesis of heparin disaccharides.

A new, powerful glycosylation method: activation of thioglycosides with dimethyl disulfide-triflic anhydride.

Dimethyl disulfide reacts with triflic anhydride to provide a highly reactive electrophile. Various thioglycosides, differing in their thio aglycons, carbohydrate units, and protecting group pattern, were activated with Me2S2-Tf2O in the presence of different glycosyl acceptors. The reactions proceeded at low temperatures within a short time, affording oligosaccharides in high yields both on primary and secondary hydroxyls. Armed and disarmed glycosyl donors were activated equally efficiently.

The potential of the molecular diversity of heparin and heparan sulfate for drug development.

Heparin and heparan sulfate have been shown to interact with a large number of biologically important proteins regulating important physiological processes. Specific oligosaccharide structures within the heterogeneous polysaccharide chains are responsible for the binding to individual proteins. Identification of specific protein-binding oligosaccharides provides lead compounds in pharmaceutical development and in one case has already resulted in an approved drug. The chemical and biosynthetic basis of the molecular diversity of heparin and heparan sulfate, its manifestation in heparin-protein interactions, and recent progress for drug development offered by this diversity are reviewed.