Alexander I. Zinin

Polarimetry as a Tool for the Study of Solutions of Chiral Solutes

Optical rotation of aqueous solutions of D-levoglucosan was studied experimentally in the 0.03-4.0 mol L(-1) concentration range and a nonlinear concentration dependence of specific optical rotation (SR) was revealed. Discontinuities observed in the concentration plot of SR (at 0.1, 0.3, 0.5, 1.0, and 2.0 mol L(-1)) are well correlated with those found by static and dynamic light scattering and identify concentration ranges in which different solution domains (supramers) may exist. The average SR experimental value for a D-levoglucosan aqueous solution ([α]D(28) -58.5±8.7 deg dm(-1) cm(-3) g(-1)) was found to be in good agreement with values obtained by theoretical calculation (TD-DFT/GIAO) of SR for 15 different conformers revealed by conformational sampling at the PCM/B3LYP/6-311++G(2d,2p)//B3LYP/6-31+G(d,p) level, which were shown to be strongly affected by the solvation microenvironment (0, 1, 2, and 3 explicit solvent molecules considered) due to local geometrical changes induced in the solute molecule. This exceptionally high sensitivity of SR makes polarimetry a unique method capable of sensing changes in the structure of supramers detected in this study.

A universal approach to the synthesis of carbohydrate conjugates of polyhedral boron compounds as potential agents for boron neutron capture therapy

A universal approach to the synthesis of carbohydrate conjugates with polyhedral boron compounds (PBCs) was developed. Oligosaccharide derivatives with amino group in aglycone moiety can be conjugated with PBC carboxy derivatives using N-methyl-N-(4,6-dimethoxy-1,3,5-triazin-2-yl)morpholinium chloride as a condensing agent. Both N-and O-glycosides differing in the conformation mobility around the glycoside bond were shown to be useful as oligosaccharides with a functional group in the aglycone moiety. This allows the application of this approach to the synthesis of PBC conjugates with a wide range of oligosaccharides isolated from natural sources can be transformed into N-glycosides with a functional group in aglycone. The approach was tested by conjugation of the carboxy derivatives of ortho-carborane and dodecaborate anion with lactose as a model oligosaccharide. Lactose, an easily available disaccharide, is a ligand of lectins expressed on the surface of melanoma cells. The approach suggested is the first example of the synthesis of such conjugates that does not require protective groups for the carbohydrate residue. It is especially important for obtaining dodecaborate-carbohydrate conjugates for which the removal of protective groups is often a non-trivial task.

1-O-Acetyl-β-d-galactopyranose: a novel substrate for the transglycosylation reaction catalyzed by the β-galactosidase from Penicillium sp.

Abstract 1- O -Acetyl-β- d -galactopyranose (AcGal), a new substrate for β-galactosidase, was synthesized in a stereoselective manner by the trichloroacetimidate procedure. Kinetic parameters ( K M and k cat ) for the hydrolysis of 1- O -acetyl-β- d -galactopyranose catalyzed by the β- d -galactosidase from Penicillium sp. were compared with similar characteristics for a number of natural and synthetic substrates. The value for k cat in the hydrolysis of AcGal was three orders of magnitude greater than for other known substrates. The β-galactosidase hydrolyzes AcGal with retention of anomeric configuration. The transglycosylation activity of the β- d -galactosidase in the reaction of AcGal and methyl β- d -galactopyranoside ( 1 ) as substrates was investigated by 1 H NMR spectroscopy and HPLC techniques. The transglycosylation product using AcGal as a substrate was β- d -galactopyranosyl-(1→6)-1- O -acetyl-β- d -galactopyranose (with a yield of ∼70%). In the case of 1 as a substrate, the main transglycosylation product was methyl β- d -galactopyranosyl-(1→6)-β- d -galactopyranoside. Methyl β- d -galactopyranosyl-(1→3)-β- d -galactopyranoside was found to be minor product in the latter reaction.

Synthesis of 3,6-di-O-methyl-β-d-glucopyranose conjugates

Abstract3,6-Di-O-methyl-β-d-glucopyranose neoglycoconjugates with bovine serum albumine and poly(acrylamide) carrier were obtained, which differ in the aglycon nature, linking pattern, and substitution degree.

Synthesis of a disaccharide of phenolic glycolipid from Mycobacterium leprae (PGL-I) and its conjugates with bovine serum albumin

Terminal disaccharide fragment of phenolic glycolipid from Mycobacterium leprae (PGL-I) was synthesized as a glycoside with 4-(2-aminoethoxy)phenyl aglycon. The obtained 4-(2-aminoethoxy)phenyl 4-O-(3,6-di-O-methyl-β-d-glucopyranosyl)-2,3-di-O-methyl-α-l-rhamnopyranoside was used for the synthesis of a series of neoglycoconjugates with bovine serum albumin with different degrees of substitution.

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.

Free Trehalose Accumulation in Dormant Mycobacterium smegmatis Cells and Its Breakdown in Early Resuscitation Phase

Under gradual acidification of growth medium resulting in the formation of dormant Mycobacterium smegmatis, a significant accumulation of free trehalose in dormant cells was observed. According to 1H- and 13C-NMR spectroscopy up to 64% of total organic substances in the dormant cell extract was represented by trehalose whilst the trehalose content in an extract of active cells taken from early stationary phase was not more than 15%. Trehalose biosynthesis during transition to the dormant state is provided by activation of genes involved in the OtsA-OtsB and TreY-TreZ pathways (according to RT-PCR). Varying the concentration of free trehalose in dormant cells by expression of MSMEG_4535 coding for trehalase we found that cell viability depends on trehalose level: cells with a high amount of trehalose survive much better than cells with a low amount. Upon resuscitation of dormant M. smegmatis, a decrease of free trehalose and an increase in glucose concentration occurred in the early period of resuscitation (after 2 h). Evidently, breakdown of trehalose by trehalase takes place at this time as a transient increase in trehalase activity was observed between 1 and 3 h of resuscitation. Activation of trehalase was not due to de novo biosynthesis but because of self-activation of the enzyme from the inactive state in dormant cells. Because, even a low concentration of ATP (2 mM) prevents self-activation of trehalase in vitro and after activation the enzyme is still sensitive to ATP we suggest that the transient character of trehalase activation in cells is due to variation in intracellular ATP concentration found in the early resuscitation period. The negative influence of the trehalase inhibitor validamycin A on the resuscitation of dormant cells proves the importance of trehalase for resuscitation. These experiments demonstrate the significance of free trehalose accumulation for the maintenance of dormant mycobacterial viability and the involvement of trehalose breakdown in early events leading to cell reactivation similar to yeast and fungal spores.

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.

Synthesis of some 2-alkoxy glyco-[2,1-d]-2-oxazolines and evaluation of their glycosylation reactivity.

The synthesis of the title compounds using intramolecular nucleophilic substitution reactions in the molecules of the corresponding 2-alkoxycarbonylamino-2-deoxy glucosyl halides was studied. It was found that in contrast to the 2-alkyl (aryl) glyco-[2,1-d]-2-oxazolines, the synthesis of the target 2-alkoxy glyco-[2,1-d]-2-oxazolines was possible only in highly basic media. The synthesized 2-alkoxy oxazoline derivatives turned out to be active glycosyl donors and were used for stereoselective 1,2-trans glycosylation reactions catalyzed by weak protic acid under very mild conditions, thus preventing anomerization and other side reactions. As a result of this glycosylation, the glycoside and oligosaccharide derivatives containing urethane N-protecting groups were formed.

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.