Olga N. Yudina

Study of glycosylation with N-trichloroacetyl-D-glucosamine derivatives in the syntheses of the spacer-armed pentasaccharides sialyl lacto-N-neotetraose and sialyl lacto-N-tetraose, their fragments, and analogues.

The syntheses of 2-aminoethyl glycosides of the pentasaccharides Neu5Ac-alpha(2-->3)-Gal-beta(1-->4)-GlcNAc-beta(1-->3)-Gal-beta(1-->4)-Glc and Neu5Ac-alpha(2-->3)-Gal-beta(1-->3)-GlcNAc-beta(1-->3)-Gal-beta(1-->4)-Glc, their asialo di-, tri-, and tetrasaccharide fragments, and analogues included a systematic study of glycosylation with variously protected mono- and disaccharide donors derived from N-trichloroacetyl-D-glucosamine of galactose, lactose, and lactosamine glycosyl acceptors bearing benzoyl protection around the OH group to be glycosylated. Despite the low reactivity of these acceptors, stereospecificity and good to excellent yields were obtained with NIS-TfOH-activated thioglycoside donors of such type, or with AgOTf-activated glycosyl bromides, while other promotors, as well as a trichloroacetimidate donor, were less effective, and a beta-acetate donor was inactive. In NIS-TfOH-promoted glycosylation with the thioglycosides, the use of TfOH in catalytic amount led to rapid formation of the corresponding oxazoline, but the quantity of TfOH necessary for further efficient coupling with an acceptor depended on the reactivity of the donor, varying from 0.07 equiv for a 3,6-di-O-benzylated monosaccharide derivative to 2.1 equiv for a peracetylated disaccharide one. In the glycosylation products, the N-trichloroacetyl group was easily converted into N-acetyl by alkaline hydrolysis followed by N-acetylation.

Synthesis of Neu5Ac- and Neu5Gc-α-(2→6′)-lactosamine 3-aminopropyl glycosides

Abstract In order to prepare 3-aminopropyl glycosides of Neu5Ac-α-(2→6′)-lactosamine trisaccharide 1 , and its N -glycolyl containing analogue Neu5Gc-α-(2→6′)-lactosamine 2 , a series of lactosamine acceptors with two, three, and four free OH groups in the galactose residue was studied in glycosylations with a conventional sialyl donor phenyl [methyl 5-acetamido-4,7,8,9-tetra- O -acetyl-3,5-dideoxy-2-thio- d - glycero -α- and β- d - galacto -2-nonulopyranosid]onates ( 3 ) and a new donor phenyl [methyl 4,7,8,9-tetra- O -acetyl-5-( N - tert -butoxycarbonylacetamido)-3,5-dideoxy-2-thio- d - glycero -α- and β- d - galacto -2-nonulopyranosid]onates ( 4 ), respectively. The lactosamine 4′,6′-diol acceptor was found to be the most efficient in glycosylation with both 3 and 4 , while imide-type donor 4 gave slightly higher yields with all acceptors, and isolation of the reaction products was more convenient. In the trisaccharides, obtained by glycosylation with donor 4 , the 5-( N - tert -butoxycarbonylacetamido) moiety in the neuraminic acid could be efficiently transformed into the desired N -glycolyl fragment, indicating that such protected oligosaccharide derivatives are valuable precursors of sialo-oligosaccharides containing N -modified analogues of Neu5Ac.

The presence of water improves reductive openings of benzylidene acetals with trimethylaminoborane and aluminium chloride

The acidic reagent formed in situ from anhydrous AlCl(3) and H(2)O in 3:1 ratio is much more efficient for the reductive openings of the cyclic benzylidene acetals with Me(3)N x BH(3) in tetrahydrofurane than the AlCl(3) alone. Under proposed conditions, the dioxane-type 4,6-O-bezylidene acetals of hexopyranosides give regioselectively the corresponding 4-hydroxy,6-O-benzyl derivatives in excellent yields. Reductive openings of the dioxolane-type 3,4-O-benzylidene acetals of galactopyranoside are also very efficient and regioselective and give either 3-O-benzyl derivative (from 3,4-O-exo-benzylidene acetal) or 4-O-benzyl derivative (from 3,4-O-endo-benzylidene acetal) depending on the configuration of the acetal carbon atom.

Synthesis of propyl and 2-aminoethyl glycosides of α-d-galactosyl-(1→3′)-β-lactoside

Abstract Propyl and 2-aminoethyl α- d -galactopyranosyl-(1→3′)-β-lactosides ( 1 and 2 ) were prepared from the corresponding perbenzylated trisaccharide allyl glycoside 6 which, in turn, was obtained by methyl triflate promoted α-galactosylation of benzylated allyl lactoside acceptor 4 with thiogalactoside 3 . Transformation of the allyl moiety in compound 6 into 2-azidoethyl one was achieved by cleavage of the double bond followed by reduction into alcohol 9 , subsequent mesylation, and mesylate→azide substitution. Alternatively trisaccharide 2 was synthesized using α-galactosylation of selectively benzoylated 2-azidoethyl lactoside 19 with 3 as the key step.

NMR and conformational studies of linear and cyclic oligo-(1→6)-β-D-glucosamines.

The conformational behavior of a series of linear and cyclic oligo-(1→6)-β-D-glucosamines and their N-acetylated derivatives, which are related to fragments of natural poly-N-acetylglucosamine, was studied by theoretical molecular modeling and experimental determination of transglycosidic vicinal coupling constants (3)J(C,H) and (3)J(H,H). Molecular dynamics simulations were performed under several types of conditions varying in the consideration of ionization of amino groups, solvent effect, and temperature. Neural network clustering and asphericity calculations were performed on the basis of molecular dynamics data. It was shown that disaccharide fragments in the studied linear oligosaccharides were not rigid, and tended to have several conformers, thus determining the overall twisted shape with helical elements. In addition, it was found that the behavior of C5-C6 bond depended significantly upon the simulation conditions. The cyclic di-, tri-, and tetrasaccharides mostly had symmetrical ring-shaped conformations. The larger cycles tended to adopt more complicated shapes, and the conformational behavior of their disaccharide fragments was close to that in the linear oligosaccharides.

New schemes for the synthesis of glycolipid oligosaccharide chains

The driving force for the constant improvement and development of synthetic methodologies in carbohydrate chemistry is the importance of natural oligosaccharide chains in numerous biological phenomena such as cell growth, differentiation, adhesion, etc. Here, we report our syntheses of the spacer-armed oligosaccharides of sialylated lacto- and neo- lacto-, globo-, ganglio-, and sulfoglucuronylparagloboside-series, which include new rationally designed synthetic blocks, efficient solutions for the stereoselective construction of glycosidic bonds, and novel protection group strategies.

Synthesis of five nona-β-(1→6)-d-glucosamines with various patterns of N-acetylation corresponding to the fragments of exopolysaccharide of Staphylococcus aureus.

A series of five 3-acetamidopropyl β-glycosides of nona-β-(1→6)-glucosamines containing two N-acetylglucosamine residues separated by a different number of glucosamine units with free amino groups have been synthesized using a convergent blockwise approach. Oxazoline glycosylation was used to introduce N-acetylglucosamine residues. These nonasaccharides are structurally related to the poly-N-acetylglucosamine (PNAG) extracellular polysaccharide of Staphylococcus aureus and can be used as models for biochemical and immunological studies.

Synthesis, NMR, and Conformational Studies of Cyclic Oligo‐(1→6)‐β‐D‐Glucosamines (Eur. J. Org. Chem. 13/2010)

The cover picture shows shows the synthesis of a novel type of functionalized cyclic oligosaccharides by unusually efficient head-to-tail intramolecular glycosylation of corresponding monohydroxy ethylthio glycosides derived from oligo-(16)-β-D-glucosamines. Detailed NMR and conformational investigations show that the carbohydrate macrocycles obtained may be regarded as convenient scaffolds for the design of conjugates with defined valency, symmetry and flexibility. The absence of a distinct hydrophobic cavity prevents the possibility of the formation of inclusion complexes as in cyclodextrins. Details are discussed in the article by N. E. Nifantiev et al. on p. 2465 ff.