Stereocontrolled 1,2-trans-arabinofuranosylation in the absence of 2-O-acyl group in glycosyl donor.

Stereocontrolled 1,2-trans-α-arabinofuranosylation using polysilylated mono- and disaccharide glycosyl donors was investigated. A complete α-stereoselectivity of 1,2-trans-arabinofuranosylation was found for Ara-β-(1 → 2)-Ara disaccharide glycosyl donors containing five triisopropylsilyl (TIPS) groups with arylthiol (1) (as shown in our previous publications) or N-phenyltrifluoroacetimidoyl (2) (this work) leaving groups. Conversely, in case of monosaccharide thioglycosides polysilylated with acyclic silyl groups (TIPS, TBDPS), stereoselectivity of glycosylation was lower (α:β = 7-8:1), although the desired α-isomer still dominated.

Unusual triflic acid-promoted oligomerization of arabinofuranosides during glycosylation.

We discovered an unusual triflic acid-promoted oligomerization of arabinofuranosides during glycosylation of the primary hydroxy group of α-(1 → 5)-linked tetraarabinofuranoside bearing 4-(2-chloroethoxy)phenyl aglycone with α-(1 → 5), β-(1 → 2)-linked tetraarabinofuranoside containing N-phenyltrifluoroacetimidoyl leaving group, which led to octa-, dodeca- and hexadecaarabinofuranosides. The possible mechanism of triflic acid-promoted oligomerization was proposed. The choice of promoter was found to be a critical factor for the discovered oligomerization of arabinofuranosides.

TIPS group-assisted isomerization of benzyl protected d-manno- and d-glucopyranose to d-fructofuranose derivatives.

Base-promoted (MeONa in MeOH or imidazole in DMF) isomerization of a series of 3,4,6-tri-O-benzyl-d-gluco- and d-mannopyranose derivatives with triisopropylsilyl (TIPS) substituents was studied. The presence of a bulky TIPS group at O-1 or O-2 was shown to be favorable for the isomerization of benzyl protected d-gluco- and d-mannopyranose derivatives to d-fructofuranose derivatives, in which the bulky silyl group occupies less sterically hindered primary position. The highest yield (33%) of the fructofuranose derivative was achieved when 3,4,6-tri-O-benzyl-2-O-triisopropylsilyl-d-mannopyranose was treated with MeONa in MeON at 50 °C.

Catalyst-free regioselective acetylation of primary hydroxy groups in partially protected and unprotected thioglycosides with acetic acid.

Highly regioselective acetylation of primary hydroxy groups in thioglycoside derivatives with - and -configurations was achieved by treatment with aqueous or anhydrous acetic acid (60-100% AcOH) at elevated temperatures (80-118 °C), avoiding complex, costly and time-consuming manipulations with protective groups. Acetylation of both 4,6--benzylidene acetals and the corresponding diols as well as the unprotected tetraol with AcOH was shown to lead selectively to formation of 6--acetyl derivatives. For example, the treatment of phenyl 1-thio-β-d-glucopyranoside with anhydrous AcOH at 80 °C for 24 h gave the corresponding 6--acetylated derivative in 47% yield (71% based on the reacted starting material) and unreacted starting tetraol in 34% yield, which can easily be recovered by silica gel chromatography and reused in further acetylation.

Preparation and in vivo evaluation of glyco-gold nanoparticles carrying synthetic mycobacterial hexaarabinofuranoside.

A number of bacterial glycans are specific markers for the detection and the serological identification of microorganisms and are also widely used as antigenic components of vaccines. The use of gold nanoparticles as carriers for glyco-epitopes is becoming an important alternative to the traditional conjugation with proteins and synthetic polymers. In this study, we aimed to prepare and evaluate in vivo glyco-gold nanoparticles (glyco-GNPs) bearing the terminal-branched hexaarabinofuranoside fragment (Ara) of arabinan domains of lipoarabinomannan and arabinogalactan, which are principal polysaccharides of the cell wall of , the causative agent of tuberculosis.

A Ring Contraction of 2,3-Di- O-Silylated Thiopyranosides To Give Thiofuranosides under Mildly Acidic Conditions.

A pyranose ring contraction of ethyl 1-thio-β-d-galactopyranosides has been discovered that proceeds with retention of aglycon under mildly acidic conditions (aq TFA in CHCl). Key factors for success of this rearrangement are the presence of bulky silyl (TIPS or TBDPS) substituents at both O-2 and O-3 and a free hydroxy group at C-4 (derivatives with acid-labile protective groups at O-4 will also engage in this reaction). The rearrangement cleanly proceeds for 2,3-di- O-TIPS derivatives with two hydroxy groups at C-4 and C-6, acid-labile TES groups at O-4 and O-6, or one acyl substituent (Bz, ClAc) at O-6.

Application of a Janus aglycon with dual function in benzyl-free synthesis of spacer-armed oligosaccharide fragments of polysaccharides from rhizobacterium Azospirillum brasilense sp7.

Both protective and pre-spacer features of 4-(2-chloroethoxy)phenyl (CEP) aglycon, which belong to the class of Janus aglycons, were engaged in a benzyl-free synthesis of oligosaccharide fragments of polysaccharides from rhizobacterium Azospirillum brasilense sp7. Introduction of α-1,4-linked L-fucose residue was performed using 3,4-di-O-benzoyl-2-O-triisopropylsilyl-α-L-fucopyranosyl N-phenyltrifluoroacetimidate in excellent stereoselectivity and high yields. The obtained deprotected di-, tri- and tetrasaccharides contain 4-(2-azidoethoxy)phenyl (AEP) spacer aglycon, which allows straightforward preparation of neoglycoconjugates that will be used for the study of the role of lipopolysaccharide of rhizobacterium A.

Arabinofuranose 1,2,5-orthobenzoate as a single precursor of linear α(1 → 5)-linked oligoarabinofuranosides.

Selectively protected mono-, di- and trisaccharide thioglycoside building blocks with unprotected primary hydroxy group at the non-reducing end, available in only one step from 3-O-benzoyl β-d-arabinofuranose 1,2,5-orthobenzoate, were used in the synthesis of linear α(1 → 5)-linked oligoarabinofuranosides up to octasaccharide. The obtained oligosaccharides contain 4-(2-chloroethoxy)phenyl (CEP) or 4-(2-azidoethoxy)phenyl (AEP) pre-spacer aglycons that allow preparation of neoglycoconjugates.

Bimodal concentration-dependent reactivity pattern of a glycosyl donor: Is the solution structure involved?

Changes in concentration (0.001-0.1 M) of an arabinofuranosyl donor (1) have been shown to modulate the temperature T at which activation of 1 occurs (from -23 °C to +7 °C), the reaction time (from 1.

The use of O-trifluoroacetyl protection and profound influence of the nature of glycosyl acceptor in benzyl-free arabinofuranosylation.

The influence of O-trifluoroacetyl (TFA) groups at different positions of thioglycoside glycosyl donors on stereoselectivity of α-arabinofuranosylation leading to corresponding disaccharides was studied. It was shown that TFA group in thioglycoside glycosyl donors, when combined with 2-O-(triisopropylsilyl) (TIPS) non-participating group, may be regarded as an electron-withdrawing protecting group that may enhance 1,2-cis-selectivity in arabinofuranosylation, the results strongly depending on the nature of glycosyl acceptor. The reactivities of the glycosyl donors were compared with those of a similar thioglycoside with O-pentafluoropropionyl groups and the known phenyl 3,5-O-(di-tert-butylsilylene)-1-thio-α-d-arabinofuranosides with 2-O-TIPS and 2-O-benzyl groups.

Synthesis of branched arabinofuranose pentasaccharide fragment of mycobacterial arabinans as 2-azidoethyl glycoside.

Branched arabinofuranose pentasaccharide with 2-azidoethyl aglycon was prepared for the first time by [3+1+1] bis-(1,2-cis)-glycosylation of trisaccharide diol with silyl-protected thioglycoside glycosyl donor. The presence of 2-azidoethyl aglycon would enable the preparation of neoglycoconjugates using the click chemistry approaches.

Ring opening of acylated β-d-arabinofuranose 1,2,5-orthobenzoates with nucleophiles allows access to novel selectively-protected arabinofuranose building blocks.

β-d-Arabinofuranose 1,2,5-orthobenzoates with 3-O-acetyl, 3-O-benzoyl, and 3-O-chloroacetyl groups were prepared in an efficient manner starting from readily available crystalline methyl 2,3,5-tri-O-benzoyl-α-d-arabinofuranoside, and ring-opening reactions of these compounds with O- and S-nucleophiles were studied. Optimized conditions leading to the formation of the respective monosaccharide adducts (up to 96% isolated yields) and to α-(1→5)-linked disaccharide thioglycosides with 5'-OH unprotected (up to 30% isolated yields) were found. Basing on these results, a novel approach for effective differentiation of 3,5-diol system and 2-hydroxy group in arabinofuranose thioglycosides was proposed.

A novel synthesis of beta-D-mannopyranosyl azide by phase transfer catalysis.

A simple stereoselective synthesis of per-O-benzoyl-beta-d-mannopyranosyl azide from per-O-benzoyl-alpha-d-mannopyranosyl bromide using phase transfer catalysis was developed. The stereochemistry at C-1 of the anomeric O-benzoylated alpha- and beta-d-mannopyranosyl azides was unambiguously established using 2D NOESY NMR spectroscopy. Pure deprotected beta-d-mannopyranosyl azide was prepared by debenzoylation with sodium methoxide in methanol.

An efficient approach towards the convergent synthesis of "fully-carbohydrate" mannodendrimers.

Glycosylation of sugar trityl ethers with sugar 1,2-O-(1-cyano)ethylidene derivatives (the trityl-cyanoethylidene condensation) has been applied to the synthesis of highly branched (dendritic) mannooligosaccharides incorporating a Manalpha1-->3(Manalpha1-->6)Man structural motif. The convergent synthetic strategy used to assemble these oligosaccharides was based on the use of glycosyl acceptors and/or a glycosyl donor already bearing this structural motif. The former were represented by mono- and ditrityl ethers of ManalphaOMe, Manalpha1-->3ManalphaOMe, and Manalpha1-->3(Manalpha1-->6)ManalphaX, where X=OMe or SEt.