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A total synthesis of the trisaccharide repeat unit of Salmonella serogroup E1 O-antigen is reported. This synthesis features a key β-mannosylation reaction via cesium carbonate-mediated anomeric O-alkylation of a partially protected D-mannose with an L-fucose-derived electrophile for the first time.

Galectins are widely expressed galactose-binding lectins implied, for example, in immune regulation, metastatic spreading, and pathogen recognition. N-Acetyllactosamine (Galβ1-4GlcNAc, LacNAc) and its oligomeric or glycosylated forms are natural ligands of galectins. To probe substrate specificity and binding mode of galectins, we synthesized a complete series of six mono-deoxyfluorinated analogues of LacNAc, in which each hydroxyl has been selectively replaced by fluorine while the anomeric position has been protected as methyl β-glycoside. Initial evaluation of their binding to human galectin-1 and -3 by ELISA and 19 F NMR T2 -filter revealed that deoxyfluorination at C3, C4' and C6' completely abolished binding to galectin-1 but very weak binding to galectin-3 was still detectable. Moreover, deoxyfluorination of C2' caused an approximately 8-fold increase in the binding affinity towards galectin-1, whereas binding to galectin-3 was essentially not affected. Lipophilicity measurement revealed that deoxyfluorination at the Gal moiety affects log P very differently compared to deoxyfluorination at the GlcNAc moiety.

L‐Hexoses are rare but biologically significant components of various important biomolecules, however, most are prohibitively expensive if commercially available, limiting their study and biotechnological exploitation. New, efficient methods to access L‐hexoses and their derivatives are thus of great interest. In a previous study, we showcased a stereoselective Bu 3 SnH‐mediated transformation of a 5‐ C ‐bromo‐D‐glucuronide to an L‐iduronide. We have now drawn inspiration from this result to derive a new methodology which can be harnessed to access other L‐hexoses. DFT calculations demonstrate that a combination of a β‐F at the anomeric position and a methoxycarbonyl substituent at C‐5 is key to optimising the selectivity for the L‐hexose product. Our investigations have also culminated in the development of the shortest known synthetic route to a derivative of L‐idose from commercially available starting material (45% yield over 3 steps). Collectively, these results address the profound lack of understanding about how to synthesise L‐hexoses in a stereoselective fashion.

A method for introducing dimethylphenylsilyl at the 4-position in carbohydrates has been developed. Two C-silylated glycosyl donors were prepared via levoglucosenone, starting from cellulose. The glycosylation properties were studied using three glucoside acceptors, a 3-OH, 4-OH, and 6-OH. Compared with the 4-deoxy variant, it was found that the anomeric selectivity was influenced more by the C-2 substituents orientation than the silyl in the 4-position. In general, the reactivity of these donors was higher than the corresponding 4-deoxy-analogue, albeit a competition experiment showed that the introduction of a C-Si increases the relative reactivity by a modest factor of around two.

The highly stereoselective synthesis of 1, 1′‐disaccharides was achieved by using 1, 2‐dihydroxyglycosyl acceptors and glycosyl donors in the presence of a tricyclic borinic acid catalyst. In this reaction, the complexation of the diols and the catalyst is crucial for the activation of glycosyl donors, as well as for the 1, 2‐cis‐configuration of the products. The anomeric stereochemistry of the glycosyl donor depends on the employed glycosyl donor. Applications of the produced 1, 1′‐disaccharides are also described.

A number of structurally diverse D-mannose-derived lactols, including various deoxy-D-mannoses and conformationally restricted bicyclic D-mannoses, have been synthesized and investigated in mechanistic studies of β-mannosylation via Cs2CO3-mediated anomeric O-alkylation. It was found that deoxy mannoses or conformationally restricted bicyclic D-mannoses are not as reactive as their corresponding parent mannose. This type of β-mannosylation proceeds efficiently when the C2-OH is left free, and protection of that leads to inferior results. NMR studies of D-mannose-derived anomeric cesium alkoxides indicated the predominance of the equatorial β-anomer after deprotonation. Reaction progress kinetic analysis suggested that monomeric cesium alkoxides be the key reactive species for alkylation with electrophiles. DFT calculations supported that oxygen atoms at C2, C3, and C6 of mannose promote the deprotonation of the anomeric hydroxyl group by Cs2CO3 and chelating interactions between Cs and these oxygen atoms favour the formation of equatorial anomeric alkoxides, leading to the highly β-selective anomeric O-alkylation. Based on experimental data and computational results, a revised mechanism for this β-mannosylation is proposed. The utilization of this β-mannosylation was demonstrated by an efficient synthesis of the hexasaccharide core of complex fucosylated N-linked glycans.

Mycobacteria infection resulting in tuberculosis (TB) is one of the top ten leading causes of death over the world, and lipoarabinomannan (LAM) has been confirmed to play significant roles in this process. In this study, a convenient synthetic approach has been developed for the synthesis of oligosaccharides derived from LAM starting with commercially available substrates and reagents. The key steps for stereoselective construction of glycosidic bonds by acceptors glycosylated with donors without neighboring participating group were achieved. It's noteworthy that enzymatic hydrolysis was applied to prepare mannose building blocks and one step of birch reaction was used to deprotect acetyl and benzyl groups as well as reduce the azide group, which can avoid multiple chemical procedures. Finally, five oligosaccharides with terminal amino group at the anomeric substituent were furnished which could be used for conjugation with proteins as potential vaccines against TB.

Unprotected aldoses in water undergo an isomerization reaction via a radical pathway when irradiated with light in the presence of water-soluble benzophenone. Whereas its anomeric carbon (C1) is oxidized to a carboxy group, the hydroxy group on the C2 carbon is replaced by hydrogen. The generated 2-deoxy lactones are readily reduced to the corresponding 2-deoxy aldoses, which are often contained in bioactive compounds.

Nucleoside configuration (α-d vs. β-d), nucleobase substituents, and the helical DNA environment of silver-mediated 5-aza-7-deazaguanine-cytosine base pairs have a strong impact on DNA stability. This has been demonstrated by investigations on oligonucleotide duplexes with silver-mediated base pairs of α-d and β-d anomeric 5-aza-7-deaza-2'-deoxyguanosines and anomeric 2'-deoxycytidines incorporated in 12-mer duplexes. To this end, a new synthetic protocol has been developed to access the pure anomers of 5-aza-7-deaza-2'-deoxyguanosine by glycosylation of either the protected nucleobase or its salt followed by separation of the glycosylation products by crystallization and chromatography. Thermal stability measurements were performed on duplexes with α-d/α-d and β-d/β-d homo base pairs or α-d/β-d and β-d/α-d hybrid pairs within two sequence environments, positions 6 or 7, of oligonucleotide duplexes. The respective Tm stability increases observed after silver ion addition differ significantly. Homo base pairs with β-d/β-d or α-d/α-d nucleoside combinations are more stable than α-d/β-d hybrid base pairs. The positional switch of silver-ion-mediated base pairs has a significant impact on stability. Nucleobase substituents introduced at the 5-position of the dC site of silver-mediated base pairs affect base pair stability to a minor extent. Our investigation might lead to applications in the construction of bioinspired nanodevices, in DNA diagnostics, or metal-DNA hybrid materials.

In this Concept article, recent advances are highlighted in the synthesis and applications of anomeric nucleophiles, a class of carbohydrates in which the C1 carbon bears a carbon–metal bond. First, the advantages of exploiting the carboanionic reactivity of carbohydrates and the methods for the synthesis of mono- and oligosaccharide stannanes are discussed. Second, recent developments in the glycosyl cross-coupling method resulting in the transfer of anomeric configuration from C1 stannanes to C-aryl glycosides are reviewed. These highly stereoretentive processes are ideally suited for the preparation of carbohydrate-based therapeutics and were demonstrated in the synthesis of antidiabetic drugs. Next, the application of the glycosyl cross-coupling method to the preparation of Se-glycosides and to glycodiversification of small molecules and peptides are highlighted. These reactions proceed with exclusive anomeric control for a broad range of substrates and tolerate carbohydrates with free hydroxyl groups. Taken together, anomeric nucleophiles have emerged as powerful tools for the synthesis of oligosaccharides and glycoconjugates and their future applications will open new possibilities to incorporate saccharides into small molecules and biologics.

In a molecular dynamics simulation study of several oligosaccharides comprising of the very basic building block of carbohydrate, the α- or β-d glucopyranose units, linked by any one of the 1-3/1-4 or 1-6 glycosidic linkages, we compare and contrast their structural and dynamical properties. Results indicate that the litheness of the oligosaccharide chain is noticeably controlled by the composition, anomeric nature and glycosidic linkage type of the units. In mixed β 1-4/1-3 d-glucopyranosides, as those found in oats and barley, the ratio of the β 1-4 and β 1-3 linked residues is crucial in determining the structural and dynamical attributes. Principal component analysis (PCA) using the internal coordinates of torsion angles subtended by glycosidic oxygen atoms and subsequent K-means clustering of the dynamical space spanned by PC1 to PC2 point to the dynamical and structural disparity in the various types of oligosaccharides studied. The properties simulated in this work are meant to provide a systematic yet comparative understanding of the importance of linkage and anomericity on the oligosaccharide chain properties and are in line with some experimental structural attributes.

The enzymatic hydrolysis of chitin, one of the most abundant carbohydrates in nature, is achieved by chitinases, enzymes of increasing importance in biomedicine and industry. Unlike most retaining glycosidases, family GH18 chitinases follow a substrate-assisted mechanism in which the 2-acetamido group of one N-acetylglucosamine monomer, rather than a basic residue of the enzyme, reacts with the sugar anomeric carbon, forming an intermediate that has been described as an oxazolinium ion. Based on QM/MM metadynamics simulations on chitinase B from Serratia marcescens, we show that the reaction intermediate of GH18 chitinases features instead a neutral oxazoline in a 4 C1 /4 H5 conformation, with an oxazolinium ion being formed on the pathway towards the reaction products. The role of a well-defined hydrogen-bond network that operates around the N-acetyl group, orchestrating catalysis by protonation events, is discussed.

A concise approach to a Neu5Ac-α-2,3-LacNPhth trisaccharide derivative was developed. First, the regio/stereoselective glycosylation between glycoside donors and glucoNPhth diol acceptors was investigated. It was found that the regioselectivity depends not only on the steric hindrance of the C2-NPhth group and the C6-OH protecting group of the glucosamine acceptors, but also on the leaving group and protecting group of the glycoside donors. Under optimized conditions, LacNPhth derivatives were synthesized in up to 92 % yield through a regio/stereoselective glycosylation between peracetylated-α-galactopyranosyl trichloroacetimidate and p-methoxyphenyl 6-O-tert-butyldiphenylsilyl-2-deoxy-2-phthalimido-β-d-glucopyranoside, avoiding the formation of glycosylated orthoesters and anomeric aglycon transfer. Then, the LacNPhth derivative was deacylated and then protected on the primary position by TBDPS to form a LacNPhth polyol acceptor. Finally, the Neu5Ac-α-2,3-LacNPhth derivative was synthesized in 48 % yield through the regio/stereoselective glycosylation between the LacNPhth polyol acceptor and a sialyl phosphite donor. Starting from d-glucosamine hydrochloride, the target Neu5Ac-α-2,3-LacNPhth derivative was synthesized in a total yield of 18.5 % over only 10 steps.

Xylobiose sequestration in a helical aromatic oligoamide capsule was evidenced by circular dichroism, NMR spectroscopy, and crystallography. The preparation of the 5 kDa oligoamide sequence was made possible by the transient use of acid-labile dimethoxybenzyl tertiary amide substituents that disrupt helical folding and prevent double helix formation. Binding of other disaccharides was not detected. Crystallographic data revealed a complex composed of a d-xylobiose alpha anomer and two water molecules accommodated in the right-handed helix. The disaccharide was found to adopt an unusual all-axial compact conformation. A dense network of 18 hydrogen bonds forms between the guest, the cavity wall, and the two water molecules.

Reported is the stereospecific cross-coupling of anomeric stannanes with symmetrical diselenides, resulting in the synthesis of selenoglycosides with exclusive anomeric control. The reaction proceeds without the need for directing groups and is compatible with free hydroxy groups as demonstrated in the preparation of glycoconjugates derived from mono-, di-, and trisaccharides and peptides (35 examples). Given its generality and broad substrate scope, the glycosyl cross-coupling method presented herein can find use in the synthesis of selenium-containing glycomimetics and glycoconjugates.

Glycosyl isoquinoline-1-carboxylate was developed as a novel benchtop stable and readily available glycosyl donor. The glycosylation reaction was promoted by the inexpensive Cu(OTf)2 salt under mild reaction conditions. The copper isoquinoline-1-carboxylate salt was precipitated from the solution and thus rendered a traceless leaving group. Surprisingly, the proton from the acceptor was absorbed by the precipitated metal complex and the reaction mixture remained at neutral pH. The copper-promoted glycosylation was also proven to be completely orthogonal to the gold-promoted glycosylation, and an iterative synthesis of oligosaccharides from benchtop stable anomeric ester building blocks becomes possible under mild reaction conditions.

Rationale Collision-induced dissociation (CID) tandem mass spectrometry is one of the major methods in the structural determination of carbohydrates. Previous experimental studies and theoretical investigation of lithiated and sodiated underivatized carbohydrates seem to indicate that dehydration reaction and cross ring dissociation of low-energy CID mainly occur at the anomeric carbon of reducing end. However, these studies only investigated few carbohydrates. Methods ESI-MS/MS spectra of [M+Li]+ and [M+Na]+ ions of several 18O1-labeled monosaccharides and disaccharides at O1 of reducing end were studied using linear ion trap mass spectrometer. Results Dissociations from the losses of both labeled and unlabeled neutral fragments were observed. The branching ratios of dissociations from the losses of unlabeled neutrals for dehydration reaction are larger than that for cross ring dissociation, lithiated carbohydrates are larger than sodiated carbohydrates, and 1-4 linkage of disaccharides are larger than the other linkages. For some lithiated carbohydrates, dehydration reaction from the losses of unlabeled neutrals has larger branching ratios than that from the losses of labeled neutrals. The fragments from the losses of unlabeled neutrals investigated using MS3 showed that the losses of unlabeled H2O mainly occurs at reducing monomer for sodiated carbohydrates, but the losses of unlabeled C2H4O2 for lithiated carbohydrates can occur at both reducing and non-reducing monomers. The ratio of B1 and Y1 ions to C1 and Z1 ions of disaccharides is related to the cis or trans configuration of the O1 and O2 atoms in the nonreducing monomer. The results are explained by the properties of transition states of dissociation channels. Conclusions Our data shows that dehydration reaction and cross ring dissociation do not always occur at the anomeric carbon atom of the reducing monomer.

Dysprosium(III) trifluoromethanesulfonate-catalyzed per-O-acetylation and regioselective anomeric de-O-acetylation of carbohydrates can be tuned by adjusting the reaction medium. In this study, the per-O-acetylation of unprotected sugars by using a near-stoichiometric amount of acetic anhydride under solvent-free conditions resulted in the exclusive formation of acetylated saccharides as anomeric mixtures, whereas anomeric de-O-acetylation in methanol resulted in a moderate-to-excellent yield. Reactions with various unprotected monosaccharides or disaccharides followed by a semi-one-pot sequential conversion into the corresponding acetylated glycosyl hemiacetal also resulted in high yields. Furthermore, the obtained hemiacetals could be successfully transformed into trichloroimidates after Dy(OTf)3 -catalyzed glycosylation.

Addition of hydroxyl radicals to the C8 position of 2'-deoxyguanosine generates an 8-hydroxyguanyl radical that can be converted into either 8-oxo-7,8-dihydro-2'-deoxyguanosine or N-(2-deoxy-d-pentofuranosyl)-N-(2,6-diamino-4-hydroxy-5-formamidopyrimidine) (Fapy-dG). The Fapy-dG adduct can adopt different conformations and in particular, can exist in an unnatural α anomeric configuration in addition to canonical β configuration. Previous studies reported that in 5'-TGN-3' sequences, Fapy-dG predominantly induced G → T transversions in both mammalian cells and Escherichia coli, suggesting that mutations could be formed either via insertion of a dA opposite the 5' dT due to primer/template misalignment or as result of direct miscoding. To address this question, single-stranded vectors containing a site-specific Fapy-dG adduct were generated to vary the identity of the 5' nucleotide. Following vector replication in primate cells (COS7), complex mutation spectra were observed that included ∼3-5% G → T transversions and ∼14-21% G → A transitions. There was no correlation apparent between the identity of the 5' nucleotide and spectra of mutations. When conditions for vector preparation were modified to favor the β anomer, frequencies of both G → T and G → A substitutions were significantly reduced. Mutation frequencies in wild-type E. coli and a mutant deficient in damage-inducible DNA polymerases were significantly lower than detected in COS7 and spectra were dominated by deletions. Thus, mutagenic bypass of Fapy-dG can proceed via mechanisms that are different from the previously proposed primer/template misalignment or direct misinsertions of dA or dT opposite to the β anomer of Fapy-dG. Environ. Mol. Mutagen. 58:182-189, 2017. © 2017 Wiley Periodicals, Inc.

Crystal structures of jacalin in complex with GlcNAc beta-(1,3) Gal-beta-OMe and Gal beta-(1,3) Gal-beta-OMe have been determined. The binding of the ligands to jacalin is similar to that of analogous -substituted disaccharides. However, the beta-substituted beta-(1,3) linked disaccharides get distorted at the anomeric center and the glycosidic linkage. The distortion results in higher internal energies of the ligands leading to lower affinity to the lectin. This confirms the possibility of using ligand distortion as a strategy for modulating binding affinity. Unlike in the case of alpha-substituted monosaccharides bound to jacalin, where a larger distortion at the anomeric center was observed, smaller distortions are distributed among two centers in the structures of the two beta-substituted beta-(1,3) linked disaccharides presented here. These disaccharides, like the unsubstituted and alpha-substituted counterparts, bind jacalin with the reducing Gal at the primary binding site, indicating that the lower binding affinity of beta-substituted disaccharides is not enough to overcome the intrinsic propensity of Gal -(1,3) Gal-based disaccharides to bind jacalin with the reducing sugar at the primary site. (C) 2017 IUBMB Life, 69(2): 72-78, 2017.

An efficient strategy for synthesis of spacer-armed tetrasaccharide related to galactan I of Klebsiella pneumoniae was reported employing newly developed acid-free conditions for pyranoside-into-furanoside (PIF) rearrangement of a digalactoside bearing 4-pentenyl group at anomeric position. The 4-pentenyl aglycon was successfully used both as a leaving group in glycosylation of 3-trifluoroacetamidopropanol, and as a temporary anomeric protection, permitting its conversion into the imidate donor. Regioselective coupling of the disaccharide blocks afforded the desired tetrasaccharide sequence required for investigation of interaction of galactan I with immune system proteins.

Herein we present a systematic study of l-rhamnosylation. The influence of protective groups, reactivity, solvents and glycosylation method, i.e. catalytic versus promoted glycosylation, are studied. It was found that the selectivity can be controlled to a large extend, by varying these parameters and hence the same donor can give both anomers. A reversal of the influence of the participating solvents is observed, and hence ethereal solvents increase the β selectivity, whereas nitrile solvents give almost exclusive α-selectively.

A practical protocol for obtaining α-glucosides was established. It was found that 4,6-O-benzylidene or 4,6-O-(di-tert-butylsilylene) tethering of glucosyl donors of the thioglycoside type enables highly α-selective glucosylation under conditions of N-iodosuccinimide (NIS)/triflic acid (TfOH) activation. The α-glucosylations were further found to be largely independent of promoter system, temperature, leaving group and anomeric configuration. The results are discussed in the context of the Glucose/Mannose paradox in glycosylation chemistry.

A detailed kinetic study of the reactions of phenylboronic acid (PhB(OH)2), 2-methylphenylboronic acid (2-MePhB(OH)2), 2-isopropylphenylboronic acid (2-iPrPhB(OH)2), and 1-hydroxy-3H-2,1-benzoxaborole (BxB(OH)) with D-fructose was carried out to clarify the nature of the reactive boron species in D-fructose sensing and investigate the corresponding reaction mechanism. Both the boronic acids (RB(OH)2) and boronate ions (RB(OH)3−) were reactive toward D-fructose, while out of the five D-fructose anomers only α-D-fructofuranose was reactive toward boron species. The reactions of all substrates proceeded consecutively in two steps (steps 1 and 2). We concluded that the first intermolecular step (step 1) corresponds to the parallel reactions (two parallel reactions for 2-iPrPhB(OH)2 and three for the other systems) of the boronic acid and the boronate ion with α-D-fructofuranose to form bicoordinate complexes (mixture of exo- and endo-isomers), and the second intramolecular step (step 2) corresponds to the formation of a tricoordinate α-D-fructofuranose complex from the bicoordinate complexes. It was found that both the boronic acid and the boronate ion were kinetically reactive toward D-fructose, with the latter being more reactive.

Nitrogen collisional cross sections (CCSs) of hybrid and complex glycans released from the glycoproteins IgG, gp120 (from human immunodeficiency virus), ovalbumin, α1-acid glycoprotein and thyroglobulin were measured with a travelling-wave ion mobility mass spectrometer using dextran as the calibrant. The utility of this instrument for isomer separation was also investigated. Some isomers, such as Man3 GlcNAc3 from chicken ovalbumin and Man3 GlcNAc3 Fuc1 from thyroglobulin could be partially resolved and identified by their negative ion fragmentation spectra obtained by collision-induced decomposition (CID). Several other larger glycans, however, although existing as isomers, produced only asymmetric rather than separated arrival time distributions (ATDs). Nevertheless, in these cases, isomers could often be detected by plotting extracted fragment ATDs of diagnostic fragment ions from the negative ion CID spectra obtained in the transfer cell of the Waters Synapt mass spectrometer. Coincidence in the drift times of all fragment ions with an asymmetric ATD profile in this work, and in the related earlier paper on high-mannose glycans, usually suggested that separations were because of conformers or anomers, whereas symmetrical ATDs of fragments showing differences in drift times indicated isomer separation. Although some significant differences in CCSs were found for the smaller isomeric glycans, the differences found for the larger compounds were usually too small to be analytically useful. Possible correlations between CCSs and structural types were also investigated, and it was found that complex glycans tended to have slightly smaller CCSs than high-mannose glycans of comparable molecular weight. In addition, biantennary glycans containing a core fucose and/or a bisecting GlcNAc residue fell on different mobility-m/z trend lines to those glycans not so substituted with both of these substituents contributing to larger CCSs. Copyright © 2016 John Wiley & Sons, Ltd.

Although the preparation of anomeric glycosylsulfonyl fluoride was unsuccessful, a tetra-O-acetylated C-glucosylpropanesulfonyl fluoride was synthesized starting from the corresponding thioacetate via sulfonate formation as the key intermediate. This sulfonyl fluoride was a bench-stable product that reacted promptly with primary and secondary alkylamines at 80 °C to give the corresponding sulfonamides in good yield. On the other hand, the same fluoride was inert toward arylamines whereas its precursor, the sulfonyl chloride, showed good reactivity. Another limitation of the acetylated sugar sulfonyl fluoride was its lack of reactivity with a multivalent aminated calixarene, this being due to acetyl transfer from the carbohydrate moiety to the amino groups of the scaffold. Fortunately, the tetra-O-benzylated C-glucosylpropanesulfonyl fluoride, prepared by the same reaction sequence employed for the synthesis of the acetylated analogue, reacted with the tetra-aminopropyl-calix[4]arene to afford the corresponding sulfonamide-linked sugar cluster in high isolated yield. A similar approach to the synthesis of calixarene-based iminosugar clusters was unsuccessful because 1-deoxynojirimycin sulfonyl fluoride derivatives could not be generated. However, a tetra-propylsulfonyl fluoride calixarene, obtained from the free-OH calix[4]arene through a three-step reaction sequence, underwent clean coupling with both C-glucosylpropylamine and N-aminopentyl-1-deoxy-deoxynojirimycin derivatives to give the corresponding tetravalent sugar and iminosugar clusters. This metal-free click reaction may constitute a valuable tool in the arsenal of ligation tools for the synthesis of multivalent carbohydrate architectures.

A stereoselective Koenigs-Knorr glycosylation reaction under the catalysis of urea is described. This method is characterized by urea-mediated hydrogen-bond activation and subsequent glycosylation with glycosyl chlorides or bromides. Excellent yields and high anomeric selectivity can be achieved in most cases. Moreover, the low α-stereoselectivity of glycosylations observed when using perbenzylated glucosyl donors can be greatly improved by the addition of tri-(2,4,6-trimethoxyphenyl)phosphine (TTMPP).

We herein report the coupling of various amides and ureas to glycosyl halides in the presence of silver triflate at room temperature. A 1:1 mixture of α/β diastereomers was obtained when alkyl/heteroaryl amides and substituted ureas were added to gluco and galacto haloglycosides. The effect of temperature, halogen, protecting group of the sugar and substituent of the amide in the overall yields and stereoselectivity of the reaction was also explored. When the acetyl-protected glucuronamide was employed in the reaction, the β anomer of the corresponding pseudodissacharide was obtained as the major isomer in good yields at room temperature. The newly synthesized compounds were subjected to viability studies using HeLa cancer cells. The results obtained are also discussed in this study.

A new and efficient approach for direct and stereoselective synthesis of β-mannopyranosides by anomeric O-alkylation has been developed. This anomeric O-alkylation of mannopyranose-derived lactols is proposed to occur under synergistic control of a kinetic anomeric effect and metal chelation. The presence of a conformationally flexible C6 oxygen atom in the sugar-derived lactol donors is required for this anomeric O-alkylation to be efficient, probably because of its chelation with cesium ion. In contrast, the presence of a C2 oxygen atom plays a minor role. This glycosylation method has been successfully utilized for the synthesis of the trisaccharide core of complex N-linked glycans.

In the current work, the investigation and development of a chemo-enzymatic approach for the synthesis of neo-glycoproteins have been studied. This strategy is based on the regioselective enzymatic hydrolysis of peracetylated monosaccharide, functionalized at the anomeric position (C1) as 1-thio-(S-cyanomethyl) group, a precursor of the 2- iminomethoxyethyl thioglycosides-linker for protein glycosylation, catalyzed by immobilized enzymes to obtain selectively monodeprotected compounds. The use of this activation in C1 is the most frequently used strategy for glycoprotein preparation. The selected biocatalysts are the lipase from Candida rugosa and the acetyl xylan esterase from Bacillus pumilus. A reversed-phase high-performance liquid-chromatographic (HPLC) method for monitoring the regioselective deprotection reaction has been developed. The developed HPLC method was used as a fingerprint to follow the hydrolysis of substrate 1 to substrate 1a and to determine its purity and yield. Moreover, the obtained compound was further purified by flash chromatography. The obtained compound 1a was further characterized using (1) H, (13) C NMR, correlation spectroscopy (COSY) and heteronuclear multiple bond correlation. The resulting product can be used as an intermediate for the preparation of di- and more complex oligosaccharides aimed at protein conjugation. Copyright © 2016 John Wiley & Sons, Ltd.

Oligosaccharide synthesis is still a challenging task despite the advent of modern glycosidation techniques. Herein, alkynyl glycosyl carbonates are shown to be stable glycosyl donors that can be activated catalytically by gold and silver salts at 25 °C in just 15 min to produce glycosides in excellent yields. Benzoyl glycosyl carbonate donors are solid compounds with a long shelf life. This operationally simple protocol was found to be highly efficient for the synthesis of nucleosides, amino acids, and phenolic and azido glycoconjugates. Repeated use of the carbonate glycosidation method enabled the highly convergent synthesis of tridecaarabinomannan in a rapid manner.

Herein, we report an efficient synthetic method for the preparation of anomeric N,N-diarylaminotetrahydropyran scaffolds. The free radical 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO)/hypervalent iodine(III)- or TEMPO/I2-mediated oxidative cyclization of tertiary amino alcohols was used to construct N,N-diarylaminotetrahydropyrans through α-C(sp3)−O bond formation, with the loss of only two H atoms. This efficient synthetic method broadens the scope of viable α-C(sp3)−H functionalized amines to include conformational-bias-free substrates.

We describe the first total syntheses of two ellagitannins, laevigatins A and E. Laevigatin A comprises a 2,3-O-(S)-hexahydroxydiphenoyl-α-D-glucose unit, whose anomeric oxygen atom forms a dehydrodigalloyl ester. Laevigatin E is a dimeric ellagitannin with structural motifs similar to those of laevigatin A. A recently developed method for synthesizing C–O digallates allowed the synthesis of more than 1 g of laevigatin A. The abundant supply allowed the synthesis of laevigatin E, an achievement that implies that more complex ellagitannins could be accessible.

Cycloadduct 1 is a conformationally constrained mimetic of the tumor-associated Tn antigen. It maintains the 4C1 conformation and the α-O-glycosidic linkage of the natural epitopes. Due to its tricyclic structure, the anomeric linkage is constrained and its conformation “frozen”. Using saturation transfer difference NMR spectroscopy experiments, epitope mapping for binding by three lectins [i.e., from Erythrina cristagalli (ECL), human macrophages (MGL), and from Helix pomatia (HPA)] was carried out. Striking differences in the epitope viewed from the ligand's perspective were revealed by this comparison. Evidently, the structural change around the C-2 position has a major impact, if the contact pattern to the ligand is not mostly restricted to galacto configuration with the axial hydroxyl group at C-4, in combination with C-3/C-6. These measurements thus provide insights into actual contacts, which help predict applicability as an inhibitor for distinct lectins, and as an elicitor of specific antibodies.

The ketosidic linkage of 3‐deoxy‐d‐manno‐octulosonic acid (Kdo) to lipid A constitutes a general structural feature of the bacterial lipopolysaccharide core. Glycosylation reactions of Kdo donors, however, are challenging due to the absence of a directing group at C‐3 and elimination reactions resulting in low yields and anomeric selectivities of the glycosides. While 3‐iodo‐Kdo fluoride donors showed excellent glycosyl donor properties for the assembly of Kdo oligomers, glycosylation of N‐acetyl‐glucosamine derivatives was not straightforward. Specifically, oxazoline formation of a β‐anomeric methyl glycoside, as well as iodonium ion transfer to an allylic aglycon was found. In addition, dehalogenation of the directing group by hydrogen atom transfer proved to be incompatible with free hydroxyl groups next to benzyl groups. In contrast, glycosylation of a suitably protected methyl 2‐acetamido‐2‐deoxy‐α‐d‐glucopyranoside derivative and subsequent deiodination proceeded in excellent yields and α‐specificity, and allowed for subsequent 4‐O‐phosphorylation. This way, the disaccharides α‐Kdo‐(2→6)‐α‐GlcNAcOMe and α‐Kdo‐(2→6)‐α‐GlcNAcOMe‐4‐phosphate were obtained in good overall yields.

The β-pyranose isomer of D-galactosylamine (1) formed complexes with three different cobalt(III) fragments. Crystals containing the dication [Co(tren)(β-D-Galp1N2H–1-κ2N1,O2)]2+ (3) showed coordination through the anomeric amino group (N1) and the deprotonated hydroxy group (O2) of the 4C1 β-pyranose form, which is also the major isomer of free galactosylamine. The cationic complexes [Co(fac-dien)(β-D-Galp1N2H–1-κ2N1,O2)]2+ (4) and [Co(phen)2(β-D-Galp1N2H–1-κ2N1,O2)]2+ (5) were analysed by NMR spectroscopy and showed the same coordination mode as 3. In terms of available ligand isomers it was shown that 1 exhibits an anomeric equilibrium in solution of both pyranose and both furanose forms as is typical for the parent glycose, galactose.

Disaccharide containing unit of peptidoglycan from bacterial cell wall, N-acetyl-d-glucosaminyl-N-acetylmuramyl-l-alanyl-d-glutaminamide (gluсosaminyl-muramyl-dipeptide) registered in Russia as an immunomodulatory drug, is shown to participate in slow equilibrium of α and β anomeric forms. Data of NMR spectra and molecular dynamics indicate that the α-anomer predominantly acquires a folded conformation stabilized by intramolecular hydrogen bond between the alanyl carbonyl and muramyl NH proton. The β-form displays a considerable fraction of extended, non-hydrogen bonded structures. In the standard immunoadjuvant test system, the α-form is practically inactive, and the activity of the equilibrium mixture with α : β = 68 : 32 ratio is due to the presence of β-anomer. Such unique α–β selectivity of biological action must be considered at the design of related immunoactive glycopeptides. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.

We have developed a versatile deprotection method for the synthesis of 2-deoxyoligosaccharides containing a 1,4-dialkylhydroquinone moiety at the anomeric position. The Birch reduction of a 2,6-dideoxy monosaccharide with potassium and 1,3-pentadiene gave the deprotected product without any undesired reduction. The utility of this method was then demonstrated in the Birch reduction of a landomycin E deoxytrisaccharide. Pd-catalysed hydrogenation led to the anomerization, or cleavage, of the glycosidic linkages. In contrast, Birch reduction based on the optimized conditions followed by treatment with mCPBA (m-chloroperoxybenzoic acid) provided the fully deprotected deoxytrisaccharide in 65 % overall yield. These results show that the Birch reduction is a powerful deprotection method for the synthesis of complex natural glycosides, including 2-deoxyoligosaccharides.