Nikita M. Podvalnyy

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.

Synthesis of hexasaccharide fragment of lipoarabonomannan from Mycobacteria: advantages of the benzyl-free approach

Spacered branched hexaarabinofuranoside, which corresponds to the terminal fragment of mycobacterial lipoarabinomannan and arabinogalactan, was synthesized via three different routes. Synthetic scheme which involved only acyl and silyl protective groups (benzyl-free approach) allows one to reduce the number of deprotection steps, enhance the overall yield, and keep the azido group until the end of the synthesis.

Glycosylation of dibutyl phosphate anion with arabinofuranosyl bromide: unusual influence of concentration of the reagents on the ratio of anomeric glycosyl phosphates formed

Glycosyl phosphates are widely used building blocks in the synthesis of various natural products, for example, nucleoside diphosphates,1—3 proteophosphoglycans,4 and С and О alkyl(aryl) glycosides5,6. Strategies of oligo saccharide synthesis using glycosyl phosphates as glycosyl donors7,8 were developed for various sugars (for example, derivatives of mannose,9 sialic acids10 and arabinofura nose11). Several known methods for the synthesis of the glyco syl phosphates are based on glysosylation reaction as the key step.3,12,13 During the synthesis (Scheme 1) of dibutyl (2,3,5 tri O benzoyl D arabinofuranosyl) phosphate (2) by glycosylation of dibutyl phosphoric acid ((BuO)2P(O)OH) with 2,3,5 tri O benzoyl α D arabinofuranosyl bromide (1)14 in MeCN in the presence of Pr2NEt 15 we found that concentration of the reagents influences the anomeric ratio of glycosyl phosphates 2. A decrease of concentration (c) of glycosyl bromide 1 (while keeping the molar ratio be tween all reagents constant) leads to an increase in the reaction stereoselectivity in favor of the α anomer 2a. A more detailed study of the concentration dependence of the stereoselectivity in a wide range of concentrations of glycosyl bromide 1 (0.001—0.2 mol L–1) revealed that the anomeric ratio of glycosyl phosphates 2 depends on con centration of the reaction mixture in a complex manner (Table 1, Fig. 1). While in the most concentrated solution (с = 0.2 mol L–1) the glycosylation proceeds unselectively (α/β = 1.5 : 1), upon transition to more diluted solutions the share of α anomer 2a increases, reaching a high value (α/β = 20 : 1) at с = 0.01 mol L–1. Upon a further de crease of concentration of glycosyl bromide 1 the stereo selectivity increases sharply (Table 1, Fig. 1) and the reac tion becomes virtually stereospecific (α/β > 50 : 1). A considerable influence of concentration of reagents on the outcome of glycosylation has been reported in sev eral cases,16—20 both the product yield16c,e,f,17,18 and stereoselectivity16e,f,17—20 as well as the reactivity16e,f,17 of the glycosyl donor being affected by dilution of the reac

4-(2-Chloroethoxy)phenol-terminated oligomerization of 3-O-benzoyl-β-d-arabinofuranose 1,2,5-orthobenzoate

A SnCl4-catalyzed reaction of 3-O-benzoyl-β-d-arabinofuranose 1,2,5-orthobenzoate with 4-(2-chloroethoxy)phenyl trimethylsilyl ether in dichloromethane gives linear arabinofuranose oligomers containing the 4-(2-chloroethoxy)phenyl aglycon.

Stereoselective sialylation with O-trifluoroacetylated thiosialosides: hydrogen bonding involved?

A series of novel sialyl donors containing O-trifluoroacetyl (TFA) groups at various positions was synthesized. The choice of protecting groups in sialyl donors was based on hypothesis that variations in ability of different acyl groups to act as hydrogen bond acceptors would influence the supramolecular structure of reaction mixture (solution structure), hence the outcome of sialylation. These glycosyl donors were examined in the model glycosylation of the primary hydroxyl group of 1,2:3,4-di-O-isopropylidene-α-D-galactopyranose in comparison with sialyl donors without O-TFA groups. The presence of O-TFA groups in a sialyl donor strongly affected the outcome of sialylation. Several sialyl donors studied showed promising results: yields of disaccharides can be as high as 86% as can be the stereoselectivities (α/β up to 15:1). The results obtained suggest that varying acyl O-protecting groups in sialyl donor may result in dramatic changes in the outcome of sialylation although further studies are required to dissect the influence of intermolecular hydrogen bonding and intramolecular substituent effects related to variations of electron-withdrawing properties of different acyl groups.

Convenient Synthesis and Purification of N-Trifluoroacetylated Neuraminic Acid Tetraol: A Key Precursor for the Synthesis of New Sialyl Donors Containing Labile O-Acyl Protecting Groups

A convenient synthesis and separation of α- and β-anomers of methyl (phenyl 3,5-dideoxy-2-thio-5-trifluoroacetamido-D-glycero-D-galacto-nonulopyranosid)onate (6a and 6b) on a multigram scale was developed. Both α- and β-isomers of 6 were obtained as crystals suitable for safe storage. The β-isomer forms a crystalline solvate with methanol. Fully O-trichloroacetylated and O-trifluoroacetylated N-trifluoroacetyl thiosialosides were synthesized in an efficient manner from the β-tetraol 6b.

Electrospray ionization mass spectra of derivatives of 2-phenylthio-N-trifluoroacetylneuraminic acid

Regularities in fragmentation of adduct ions [M + NH4]+ and [M + Na]+ of N-trifluoroacetyl neuraminic acid phenyl thioglycosides under collisionally-induced decay (CID) activation are studied. For [M + Na]+ ions, elimination of the C8H8O2S fragment (along with thiophenol molecule) proceeds both in the presence or the absence of an acetyl group, whereas for the [M + NH4]+ ion, elimination of thiophenol C6H6S is observed. Similar elimination of the C8H8O2S fragment has been observed previously only for cationized molecules of phenylthioglycoside acetates of hexoses.