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Two couples of dicationic ionic liquids, featuring pyrrolidinium and piperidinium cations and different linker chains, were prepared and characterized. 1,1′-(propane-1,3-diyl)bis(1-methylpyrrolidinium) bromide, 1,1′-(octane-1,8-diyl)bis(1-methylpyrrolidinium) bromide, 1,1′-(propane-1,3-diyl)bis(1-methylpiperidinium) bromide, and 1,1′-(octane-1,8-diyl)bis(1-methylpiperidinium) bromide were synthesized in quantitative yields and high purity and thermally characterized through TGA and DSC analysis. In this study, we propose a preliminary comparative evaluation of the effect of the linker chain length and of the size of the aliphatic ammonium ring on the thermal and solubility properties of bromide dicationic ionic liquids.

Solvatochromic probes are often used to understand solvation environments at the molecular scale. In the case of ionic liquids constituted by an anion and a cation, which are designed and paired in order to obtain a low melting point and other desirable physicochemical properties, these two indivisible components can interact in a very different way with the probe. This is the case with one of the most common probes: Reichardt’s Dye. In the cases where the positive charge of the cation is delocalized on an aromatic ring such as imidazolium, the antibonding orbitals of the positively charged aromatic system are very similar in nature and energy to the LUMO of Reichardt’s Dye. This leads to an interesting, specific cation-probe interaction that can be used to elucidate the nature of the ionic liquids’ cations. Parallel computational and experimental investigations have been conducted to elucidate the nature of this interaction with respect to the molecular structure of the cation.

This study reports an ionic liquid (IL) promoted green method to obtain diaryl thioethers useful as key intermediates for the synthesis of matrix metalloproteinase (MMP) inhibitors. The synthetic pathway includes a sequential Ullmann reaction and Suzuki cross-coupling. The Ullmann conditions were optimized as regards the catalyst, the ionic liquid, reaction time, and temperature. Under optimal conditions (1-butyl-3-methylimidazolium bromide ([BMIM]Br) as solvent; catalyst, Cu; base, K2CO3; reaction time, 22 h; reaction temperature, 150°C) the aryl iodide conversion was 95%. The Suzuki cross-coupling was conducted in 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM]BF4) at 110°C, using Pd(PPh3)4 as catalyst and Na2CO3 as base. For both reactions, a combination of ILs with microwave (MW) irradiation determined a substantial improvement of reaction time and yields compared to conventional heating. This multi-step process reduces reaction times and removes organic solvents providing a more eco-friendly alternative for the synthesis of important pharmaceutical building blocks.

We previously reported the 2-oxopyridine-3-carboxamide derivative EC21a as the first small synthetic CB2R positive allosteric modulator which displayed antinociceptive activity in vivo in an experimental mouse model of neuropathic pain. Herein, we extended the structure-activity relationships of EC21a through structural modifications regarding the p-fluoro benzyl moiety at position 1 and the amide group in position 3 of the central core. The characterization in vitro was assessed through radioligand binding experiments and functional assays (GTPγS, cAMP, βarrestin2). Among the new compounds, the derivatives A1 (SV-10a) and A5 (SB-13a) characterized respectively by fluorine atom or by chlorine atom in ortho position of the benzylic group at position 1 and by a cycloheptane-carboxamide at position 3 of the central core, showed positive allosteric behavior on CB2R. They enhanced the efficacy of CP55,940 in [35S]GTPγS assay, and modulated CP55,940-dependent βarrestin2 recruitment and cAMP inhibition. The obtained results extend our knowledge of the structural requirements for interaction with the allosteric site of CB2R.

ADAMTS-5 is a major protease involved in the turnover of proteoglycans such as aggrecan and versican. Dysregulated aggrecanase activity of ADAMTS-5 has been directly linked to the etiology of osteoarthritis (OA). For this reason, ADAMTS-5 is a pharmaceutical target for the treatment of OA. ADAMTS-5 shares high structural and functional similarities with ADAMTS-4, which makes the design of selective inhibitors particularly challenging. Here we exploited the ADAMTS-5 binding capacity of β-N-acetyl-d-glucosamine to design a new class of sugar-based arylsulfonamides. Our most promising compound, 4b, is a non-zinc binding ADAMTS-5 inhibitor which showed high selectivity over ADAMTS-4. Docking calculations combined with molecular dynamics simulations demonstrated that 4b is a cross-domain inhibitor that targets the interface of the metalloproteinase and disintegrin-like domains. Furthermore, the interaction between 4b and the ADAMTS-5 Dis domain is mediated by hydrogen bonds between the sugar moiety and two lysine residues (K532 and K533). Targeted mutagenesis of these two residues confirmed their importance both for versicanase activity and inhibitor binding. This positively-charged cluster of ADAMTS-5 represents a previously unknown substrate-binding site (exosite) which is critical for substrate recognition and can therefore be targeted for the development of selective ADAMTS-5 inhibitors.

A microwave (MW)/deep eutectic solvent (DES)-assisted (MWDA) extraction process for obtaining value-added compounds from chestnut shell waste (CSW) is presented. DESs were used as green solvents featuring both high biomass dissolution ability and good response to MW irradiation. A survey of different acid-based DESs led to the identification of Choline Chloride (ChCl)-oxalic acid as the system most sensitive to experimental design variations, especially when considering the total phenolic content (TPC) and the total mass amount recovered (yield wt%). Hence, the MW absorption properties of ChCl-oxalic acid dihydrate and ChCl-oxalic acid DESs, as single components and in mixture with water, were assessed by the experimental determination of their MW heating response. Moreover, the extraction efficiency for the best MW responding system, ChCl-oxalic acid dihydrate, was evaluated at different MW-irradiation times and extraction temperatures. The isolated polyphenols from CSW were further characterized by HPLC-DAD analysis. Gallic acid, ellagic acid, catechin hydrate and procyanidin B2 were identified and quantified, with their relative ratios varying as a function of the MWDA extraction conditions. Lignin, hemicellulose and cellulose compositions of the solid residues of CSW after the MWDA extraction were assessed using a cross validation model obtained by partial least squares regression (PLS) of their FTIR spectra. The chemometrics results, corroborated by SEM analyses, highlighted the ability of the oxalic acid-based DES to simultaneously remove lignin during polyphenol extraction. Overall, the MWDA extraction process presented here enables the fast, cheap and tunable processing of food waste yielding a high amount of valuable bioactive compounds. This journal is

Two series of ionic liquids (ILs) consisting in metal-EDTA complex anions ([MEDTA], with V, Cr, Mn, Fe and Co as metal center) and 1-butyl-3-methylimidazolium ([BMIM]) or trioctylmethylphosphonium ([TOMP]) cations have been prepared via a new synthetic approach based on the related acidic EDTA complexes (HMEDTA). A strong influence of both the coordinated metal and the cation type on the thermal behavior of the obtained ILs was assessed through DSC and TGA, while the solubility features were found to be primarily affected by the cation nature. The observed solubility results for [TOMP] series ILs in organic solvents showed the preparation of ILs as an effective way to solubilize metal-EDTA complexes into non-aqueous solutions, opening new investigation potential and applicative perspectives. The electrochemical properties of the synthesized ILs have been studied both in aqueous and non-aqueous environments, providing insights on the strong solvent effect on metal-EDTA complexes electrochemistry and, for many of the ILs, showing promising characteristics for electrochemical applications both in water and in organic solvents.

Aldose reductase is a key enzyme in the development of long term diabetic complications and its inhibition represents a viable therapeutic solution for people affected by these pathologies. Therefore, the search for effective aldose reductase inhibitors is a timely and pressing challenge. Herein we describe the access to a novel class of oxyimino derivatives, obtained by reaction of a 1,5-dicarbonyl substrate with O-(arylmethyl)hydroxylamines. The synthesised compounds proved to be active against the target enzyme. The best performing inhibitor, compound (Z)-8, proved also to reduce both cell death and the apoptotic process when tested in an in vitro model of diabetic retinopathy made of photoreceptor-like 661w cell line exposed to high-glucose medium, counteracting oxidative stress triggered by hyperglycaemic conditions.

Multiple sclerosis is a chronic inflammatory demyelinating disorder of the central nervous system that eventually leads to progressive neurodegeneration and disability. Recent findings highlighted the emerging role of each target of the endocannabinoid system in controlling the symptoms and disease progression of multiple sclerosis. Therefore, multi-target modulators of the endocannabinoid system could provide a more effective pharmacological strategy as compared to the single target modulation. In this work, N-cycloheptyl-1,2-dihydro-5-bromo-1-(4-fluorobenzyl)-6-methyl-2-oxo-pyridine-3-carboxamide (B2) was identified as the most promising compound with dual agonism at cannabinoid receptors type-1 and cannabinoid receptors type-2 and good drug-like properties. In in vitro assays, B2 reduced glutamate release from rat synaptosomes through interaction with cannabinoid receptors type-1 and modulated the production of the pro- and anti-inflammatory cytokines (interleukins IL-1β and IL-6 and interleukin IL-10 respectively) via cannabinoid receptors type-2 activation. Furthermore, B2 demonstrated antinociceptive effects in an animal model of neuropathic pain and efficacy in an experimental autoimmune encephalomyelitis model of multiple sclerosis.

The development of microwave (MW) assisted processes involving the use of deep eutectic solvents (DESs) is a fast-expanding research topic. However, there is a lack of information about the heating behavior of DESs under MW irradiation. In this work, a family of DESs composed by choline chloride and two types of hydrogen bond donors (carboxylic acids or polyols) was prepared and its MW heating response and thermal heating behavior were investigated as well as compared to that of the single components. The MW absorption properties were explored using different MW applied power at fixed MW irradiation times. The thermal behavior and the analysis of the evolved gases during the DESs thermal decomposition were assessed by TG-FTIR analysis. A strong interaction of DESs with MWs was found in all cases. Polyol-based DESs showed the highest MW response, ChCl-glycerol being the best MW absorbing system. The thermal heating behavior revealed that a decomposition process of entire DES occurred rather than a sum of evaporation steps of their single components. This decomposition can be ascribed to a synergy effect of heating and H-bond acidity strength in DESs network. Different thermal decomposition pathways for all DESs were thus proposed. All studied DESs showed thermal decomposition behavior and MW absorption properties more similar to ionic liquids (ILs) than molecular solvents. These unique properties make DESs suitable green solvents for the development of MW assisted chemical processes.

The full utilization of agricultural waste and its recycle into a new chain of value are of primary importance for the development of a sustainable and profitable agricultural industry. Chestnut sh...

Objectives Ionic liquids have shown potential for applications as antimicrobials. Their antimicrobial activity has been shown to be higher against Gram-positive than Gram-negative bacteria, suggesting a protective role for the outer membrane of Gram-negative microorganisms. Colistin is a last-resort antibiotic often used for treating infections sustained by multi-drug resistant Gram-negative bacteria. Colistin interacts with the bacterial lipopolysaccharide, thus altering the structure and increasing the permeability of the outer membrane. The aim of this study was to investigate the interaction between colistin and the ionic liquids 1-methyl-3-dodecylimidazolium bromide, 1-dodecyl-1-methylpyrrolidinium bromide, and 1-dodecyl-1-methylpiperidinium bromide against Gram-negative bacteria of clinical importance such asEscherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Methods The interaction between colistin and ionic liquids against Gram-negative bacteria was evaluated by the checkerboard assay. Bacterial killing assays againstP. aeruginosa were carried out to assess whether the synergistic combinations were bactericidal. Results The results of checkerboard assays showed that all three ionic liquids interacted synergistically with colistin againstK. pneumoniae, P. aeruginosa, and A. baumannii but not against Escherichia coli, which resulted more sensitive to all three ionic liquids compared to the other tested species. The synergistic combinations showed no hemolytic activity. Bacterial killing assays showed that the synergistic effect between colistin and each one of the three tested ionic liquids against P. aeruginosa was bactericidal. Conclusion Overall, the results obtained suggest that colistin and ionic liquids might be used in combination for possible applications to combat infections sustained by multi-drug resistant Gram-negative bacteria.

Zwitterionic polysaccharides (ZPs) have been shown in recent years to display peculiar immunological properties, thus attracting the interest of the carbohydrate research community. To fully elucidate the mechanisms underlying these properties and exploit the potential of this kind of structures, in depth studies are still required. In this context, the preparation of two cationic, an anionic, as well as two zwitterionic tetrasaccharide analogues of the smallest immunogenic structure of Streptococcus pneumoniae type 14 (SP14) capsular polysaccharide are presented. By exploiting a block strategy, the negative charge has been installed on the non-reducing end of the lactose unit of the tetrasaccharide and the positive charge either on the non-reducing end of the lactosamine moiety or on an external linker. These structures have then been tested by competitive ELISA, showing that the structural variations we made do not modify the affinity of the neutral compound to binding to a specific antibody. However, lower efficacies than the natural SP14 compound were observed. The results obtained, although promising, point to the need to further elongate the polysaccharide structure, which is likely too short to cover the entire epitopes.

Diabetes is a multi-factorial disorder that should be treated with multi-effective compounds. Here we describe the access to polyhydroxylated pyrrolidines, belonging to the d-gluco and d-galacto series, through aminocyclization reactions of two differentially protected d-xylo-hexos-4-ulose derivatives. The prepared compounds proved to inhibit both alpha-glucosidase, responsible for the emergence of hyperglycemic spikes, and aldose reductase, accountable for the development of abnormalities in diabetic tissues. Accordingly, they show the dual inhibitory profile deemed as ideal for diabetes treatment. Significantly, compound 17b reduced the process of cell death and restored the physiological levels of oxidative stress when tested in the photoreceptor-like 661w cell line, thus proving to be effective in an in vitro model of diabetic retinopathy.

Iminosugars are known glycosidase inhibitors which are the subject of drug development efforts against several diseases. The access to structurally-related families of iminosugars is of primary importance for running structure-activity relationship studies. In this work, the double reductive amination (aminocyclization) reaction of a dicarbonyl derivative of the l-arabino series, in turn obtained from lactose, is reported. Different ratios of 1,6-di-deoxy-d-galacto and 1,6-di-deoxy-l-altro nojirimycin derivatives were obtained depending on the amine employed in this transformation which provided an insight into the effects of their structure on the outcome of the reaction. Of particular interest were the results obtained when two enantiomeric amino acids (d-Phe-OMe and l-Phe-OMe) were used, which resulted in the inversion of the reaction stereoselectivity.

Ten new iridoid glycosides (1-10) and two new monoterpenoids (11 and 12), together with nine known compounds (13-21), were isolated from the n-butanol extract of the aerial parts of Anarrhinum pedatum. The structural characterization of all compounds was performed by spectroscopic analysis, including 1D and 2D NMR and HRESIMS experiments. The isolates were assayed for their antiangiogenic activity by two in vivo models, using zebrafish embryos and chicken chorioallantoic membranes (CAMs). The results showed that among the new compounds 6'- O-menthiafoloylmussaenosidic acid-11-(5- O-β-d-fructopyranosyl) ester (9) exhibited the most potent antiangiogenic activity in both the zebrafish embryos and CAM assays, reducing the growth of blood vessels. Antiangiogenic effects were also observed for the known compounds 6- O-nerol-8-oyl-antirrinoside (13), antirrinoside (14), 6- O- trans- and cis- p-coumaroyl antirrinoside (15), and (6 S)-2 E-2,6-dimethyl-6-hydroxyocta-2,7-dienoic acid β-glucopyranosyl ester (18).

In order to identify most suitable ionic liquids (ILs) for potential applications in infection prevention and control, in the present study we comparatively evaluated the antimicrobial potency and hemolytic activity of 15 ILs, including 11 previously described and four newly synthesized ILs, using standard microbiological procedures against Gram-positive and Gram-negative bacteria. ILs showing the lowest minimum inhibitory concentration (MIC) were tested for their hemolytic activity. Three ILs characterized by low MIC values and low hemolytic activity, namely 1-methyl-3-dodecylimidazolium bromide, 1-dodecyl-1-methylpyrrolidinium bromide, and 1-dodecyl-1-methylpiperidinium bromide were further investigated to determine their minimum bactericidal concentration (MBC), and their ability to inhibit biofilm formation by Staphylococcus aureus or Pseudomonas aeruginosa. Killing kinetics results revealed that both Gram-positive and Gram-negative bacteria are rapidly killed after exposure to MBC of the selected ILs. Furthermore, the selected ILs efficiently inhibited biofilm formation by S. aureus or P. aeruginosa. To our knowledge, this is the first systematic study investigating the antimicrobial potential of different types of ionic liquids using standard microbiological procedures. In the overall, the selected ILs showed low hemolytic and powerful antimicrobial activity, and efficient inhibition of biofilm formation, especially against S. aureus, suggesting their possible application as anti-biofilm agents.

New thiol-functionalized carboxylate ionic liquids (ILs), varying both for the cation and for the anion structures, have been prepared as new potential redox switching systems by reacting either 3-mercapto propionic acid (3-MPA) or N-acetyl-cysteine (NAC) with commercially available methyl carbonate ILs. Different ratios of thiol/disulfide ILs were obtained depending both on the acid employed in the neutralization reaction and on the reaction conditions used. Surprisingly, the imidazolium ILs displayed limited thermal stability which resulted in the formation of an imidazole 2-thione and a new sulfide ionic liquid. Conversely, the formation of the imidazole 2-thione was not observed when phosphonium disulfide ILs were heated, thus confirming the involvement of the imidazolium ring in an unexpected side reaction. An insight into the mechanism of the decomposition has been provided by means of DFT calculations.

Selective and potent matrix metalloproteinase 12 (MMP-12) inhibitors endowed with improved hydrophilicity are highly sought for potential use in the treatment of lung and cardiovascular diseases. In the present paper, we modified the structure of a nanomolar MMP-12 inhibitor by incorporating an ionic liquid (IL) moiety to improve aqueous solubility. Four biologically active salts were obtained by linking the sulfonamide moiety of the MMP-12 inhibitor to imidazolium-, pyrrolidinium-, piperidinium-, and DABCO-based ILs. The imidazolium-based bioactive salt was tested on human recombinant MMPs and on monocyte-derived dendritic cells, showing activity similar to that of the parent compound, but improved water solubility. The imidazolium-based bioactive salt was then used to prepare electrostatically stabilized MMP inhibitor-coated gold nanoparticles (AuNPs) able to selectively bind MMP-12. These AuNPs were used to study subcellular localization of MMP-12 in monocyte-derived dendritic cells by transmission electron microscopy analysis.

The third generation of glycoconjugated azo dyes (GADs) was prepared linking monoazo dyes to 6-amino-6-deoxy-d-galactose or 6′amino-6′-deoxylactose through mixed amido-ester connections. The complementary conjugation reactions were studied using the succinyl derivative of either the acetal protected aminosugar or the azo dye. Target “naturalized” GADs were obtained after acid hydrolysis of the acetal protecting groups present on the sugar moiety.

The synthesis of β-D-GlcNAc-, β-D-GalNAc-, β-D-ManNAc-, and β-D-TalNAc-(14)-DNJ iminosugar disaccharides has been achieved, avoiding the glycosylation reaction, using a mixed tetracetonide of lactose [2,3:5,6:3′,4′-tri-O-isopropylidene-(6′-O-2-methoxy-2-methylethyl)-lactose dimethyl acetal] as starting material. The synthetic process is based on the transformation of the reducing unit of suitably protected β-D-hexosaminyl-(14)-aldehydo-D-glucose dimethyl acetal disaccharides into a deoxynojirimycin derivative. Key steps of the synthesis are: (a) the selective oxidation of the 5-position of the D-glucose unit, (b) release of the aldehydo function, (c) double reductive aminocyclisation of the 1,5-dicarbonyl disaccharide intermediate, and (d) complete deprotection.

The stereoselective preparation of the β- d -GlcNAc-(1 → 4)- d -Glc disaccharide starting from known 4-O-[6-O-(1-methoxy-1-methylethyl)-3,4-O-isopropylidene-β- d -talopyranosyl]-2,3:5,6-di-O-isopropylidene-aldehydo- d -glucose dimethyl acetal (2), in turn easily obtained from lactose, is reported. Key steps of this new procedure, that avoids the glycosylation reaction, are (a) a first epimerization at C-4′ through an unusual procedure involving a completely stereospecific hydroboration–oxidation of the enol ether group of the hex-4-enopyranoside 4, obtained from 3 by base promoted acetone elimination, (b) an amination with inversion by SN2 reaction on an imidazylate intermediate, and, finally, (c) N-acetylation followed by complete deprotection.

Conjugation of known biologically active molecules to carbohydrate frameworks represents a valuable option for the preparation of hybrid, structurally-related families of compounds with the aim of modulating their biological response. Therefore, we present here a study on the preparation of d-galacto, d-manno, d-gluco, and d-lactose glycoconjugates of an established N-hydroxyindole-based (NHI) inhibitor of lactated dehydrogenase (LDH). Structural variations involved the sugar stereochemistry and size as well as the anchoring point of the NHI on the carbohydrate frame (either C-1 or C-6). In the case of the galactose anomeric glycoconjugate (C-1), intriguing solvent-dependent effects were observed in the glycosylation stereochemical outcome. The biological activity of the deprotected glycoconjugates in contrasting lactate formation and cancer cell proliferation are described.

Carbohydrate mimics have been studied for a long time as useful sugar substitutes, both in the investigation of biological events and in the treatment of sugar-related diseases. Here we report further evaluation of the capabilities of inositols as carbohydrate substitutes. The conformational features of an inositol-model of a simplified repeating unit corresponding to the capsular polysaccharide of Streptococcus pneumoniae 19F has been evaluated by computational analysis, and compared to the native repeating unit. The inositol mimic was synthesized, and its experimental spectroscopic data allowed for verification of the theoretical results.

Primary tosylates 1a-d were converted to the corresponding amino species 3a-d. Benzylamine was proved effective for the substitution of tosylates, using acetonitrile (MeCN) as the solvent of choice and citric acid to remove excess of the reagent from crude products 2a-d. Debenzylation was carried out at circa (ca.) atmospheric pressure of hydrogen gas in the presence of acetic acid (AcOH). The method was also demonstrated in a demo batch experiment for the synthesis of compound 3a on a 50 g scale of 1a.

Matrix metalloproteinase-12 (MMP-12) can be considered an attractive target to study selective inhibitors useful in the development of new therapies for lung and cardiovascular diseases. In this study, a new series of arylsulfonamide carboxylates, with increased hydrophilicity resulting from conjugation with a β-N-acetyl-d-glucosamine moiety, were designed and synthesized as MMP-12 selective inhibitors. Their inhibitory activity was evaluated on human MMPs by using the fluorimetric assay, and a crystallographic analysis was performed to characterize their binding mode. Among these glycoconjugates, a nanomolar MMP-12 inhibitor with improved water solubility, compound 3 [(R)-2-(N-(2-(3-(2-acetamido-2-deoxy-β-d-glucopyranosyl)thioureido)ethyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid], was identified.

Available online 8 June 2010 This article has been retracted: please see Elsevier Policy on Article Withdrawal ( http://www.elsevier.com/locate/withdrawalpolicy ). This paper is being retracted at the request of the majority of authors, who discovered after the publication that some data is unreliable, as described below. The above paper describes synthesis of glycosyl derivatives of deoxynojirimycin (DNJ), e.g. β-D-Tal-NAc-(1→4)-DNJ and β-D-ManNAc-(1→4)-DNJ. The compounds were fully characterized by MS, NMR and chiroptical methods. The affinity to the rat receptor NKR-P1 and human receptor CD69 has been evaluated. Unfortunately, we have learned recently that the author responsible for the immunological experiments – Prof. Karel Bezouska - has been fabricating the results and also manipulating experimental material in collaborating laboratories. Based on the findings of the joint ethical committee of the Institute of Microbiology, Acad. Sci. of the Czech Republic, and Charles University in Prague and based on the extensive re-evaluation experiments [1, 2] done by us we consider all the data on the binding of carbohydrates to the NKR-P1 and CD69 receptors erroneous and, therefore, we propose corrigendum or retraction the above publication. We would like to state that all synthetic work in this paper, namely the synthesis of compounds 4-11 including all spectral characteristics (NMR, MS) was not affected by the misconduct and, therefore, remains valid. We would like to apologize to all affected parties. V. Kren, Corresponding author [1] D. Rozbeský, J. Krejzova, K. Křenek, J. Prchal, R. Hrabal, M. Kžisek, L. Weignerova, M. Fiore, P. Dumy, O. Renaudet, V. Křen: Reevaluation of Binding Properties of Recombinant Lymphocyte Receptors NKR-P1A and CD69 to Chemically Synthesized Glycans and Peptides. Int. J. Mol. Sci. 15, 1271-1283 (2014). [2] V. Grobarova, V. Benson, D. Rozbesky, P. Novak, J. Cerny: Re-evaluation of the involvement of NK cells and C-type lectin-like NK-receptors in modulation of immune responses by multivalentGlcNAc-terminated oligosaccharides. Immunol. Lett. 156, 110-117 (2013).

The transformation of (5 R )-2,6-di- O -benzyl-5- C -methoxy-β- d -galactopyranosyl-(1→4)-2,3:5,6-di- O -isopropylidene- aldehydo - d -glucose dimethyl acetal ( 8 ) into partially protected derivatives of d - xylo - and l - lyxo -aldohexos-5-ulose has been reported, applying appropriate epimerisation methods to its 3′- O - and 4′- O -protected alcoholic derivatives.

A series of carbamides derived from 1,2:5,6-di-O-isopropylidene-D-gluco- and D-allofuranose as well as their 5,6-O-deprotected analogues (2 and 4) and methyl 3,4-O-isopropylidene-alpha- and beta-D-galactopyranosides (5 and 6) have been prepared in order to evaluate their ability to induce erythroid differentiation of human erythroleukemic K562 cells. Twenty out of 51 carbamides tested exhibit an appreciable activity as inducers of erythroid differentiation and have been fully characterized and described.

A new stereoselective preparation of N -aceyl- d -galactosamine ( 1b ) starting from the known p -methoxyphenyl 3,4- O -isopropylidene-6- O -(1-methoxy-1-methylethyl)-β- d -galactopyranoside ( 10 ) is described using a simple strategy based on (a) epimerization at C-2 of 10 via oxidation–reduction to give the talo derivative 11 , (b) amination with configurational inversion at C-2 of 11 via a S N 2-type reaction on its 2-imidazylate, (c) anomeric deprotection of the p -methoxyphenyl β- d -galactosamine glycoside 14 , (d) complete deprotection. Applying the same protocol to 2,3:5,6:3′,4′-tri- O -isopropylidene-6′- O -(1-methoxy-1-methylethyl)-lactose dimethyl acetal ( 4 ), directly obtained through acetonation of lactose, the disaccharide β- d -GalNAc p -(1→4)- d -Glc p ( 1a ) was obtained with complete stereoselectivity in good (40%) overall yield from lactose.

The intramolecular aldol condensation of aldohexos-5-ulose derivatives of the D-xylo and L-ribo stereoseries has been studied. Only one of the four possible inososes was isolated from both stereoseries in reasonable yields (30–38%). The results obtained, together with the previous findings for the L-arabino and L-lyxo stereoseries, allowed for the rationalisation of a mechanism of the reaction based on open-transition-state models and electron-withdrawing inductive effects. Complementary reductions of the intermediate inososes were possible by changing the reaction conditions, and two isomeric inositol derivatives were obtained with complete stereoselection from each inosose. The presented approach permits us to control the configuration of three out of the six stereocentres of the inositol frame and gives access to seven of the nine inositols. Noteworthy, for the D-xylo derivative, the two-step sequence (condensation followed by reduction with NaBH(OAc)3) represents the biomimetic synthesis of myo-inositol. Furthermore, the sugar-based pathway leads directly to enantiomerically pure selectively protected inositols and does not require any desymmetrisation procedure which is needed when myo-inositol and other achiral precursors are employed as starting materials. As an example of application of the method, the indirect selective protection of secondary inositols’ hydroxy functions, by placing specific protecting groups on the aldohexos-5-ulose precursor has been presented.

We report a process to naturalise synthetic azodyes through their linkage with lactose, or its monosaccharide components, either galactose or glucose, to enhance their solubility, as many other natural dyes. This modification allows the dyeing process of textile materials to take place in water without the addition of surfactants or other additives. The synthesis of the first generation of glycoazodyes (GADs) is carried out with the use of a diester linker to bond the azodye and the sugar. Preliminary tinctorial tests showed that this first generation of GADs is soluble in water and that these new dyes are multipurpose and are able to dye different fabrics well.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)