Galactose Derivatives Research Articles

Design and Synthesis of Dual Galectin-3 and EGFR Inhibitors Against Liver Fibrosis.

Liver fibrosis, mainly arising from chronic viral or metabolic liver diseases, is a significant global health concern. There is currently only one FDA-approved drug (Resmetirom) in the market to combat liver fibrosis. Both galectin-3 and epidermal growth factor receptor (EGFR) play important roles in liver fibrosis, while galectin-3 may interact with EGFR. Galectin-3 inhibitors, typically lactose or galactose derivatives may inhibit liver fibrosis. We hypothesized that targeting both galectin-3 and EGFR may have better effect against liver fibrosis. Here, EGFR inhibitor erlotinib was used in a series of designed galectin-3 inhibitors after hybridization with the pharmacophore structure in reported galectin-3 inhibitors to impede hepatic stellate cells (HSCs) activation by a typical method of click chemistry. Bioactivity test results showed that compound 29 suppressed TGF-β-induced upregulation of fibrotic markers (α-SMA, fibronectin-1, and collagen I). The preferred compound 29 displayed better binding to galectin-3 (KD = 52.29 μM) and EGFR protein (KD = 3.31 μM) by SPR assay. Further docking studies were performed to clarify the possible binding mode of compound 29 with galectin-3 and EGFR. Taken together, these results suggested that compound 29 could be a potential dual galectin-3 and EGFR inhibitor as leading compound for anti-liver fibrosis new drug development.

Mechanistic Insights into Nitrite Degradation by Metabolites of L. plantarum A50: An LC-MS-Based Untargeted Metabolomics Analysis

Nitrites are universally acknowledged natural toxic substances that frequently lead to poisoning in humans and animals. During fermentation, certain microorganisms utilize a portion of the nitrogen element and reduce nitrates to nitrites through specific metabolic pathways. In this study, a highly effective lactic acid bacterial strain, Lactiplantibacillus plantarum A50, was isolated and screened from alfalfa silage for its remarkable ability to degrade nitrites. L. plantarum A50 exhibits exceptional nitrite removal capacity, with a degradation rate of 99.06% within 24 h. Furthermore, L. plantarum A50 demonstrates normal growth under pH values ranging from 4 to 9 and salt concentrations of 5%, displaying excellent tolerance to acidity, alkalinity, and salinity. Additionally, it undergoes fermentation using various carbon sources. Within the first 6–12 h of culture, L. plantarum A50 primarily achieves nitrite degradation through non-acidic processes, resulting in a degradation rate of 82.67% by the 12th hour. Moreover, the metabolites produced by L. plantarum A50 exhibit a synergistic interaction with acidity, leading to a nitrite degradation rate of 98.48% within 24 h. Notably, both L. plantarum A50 and MRS broth were found to degrade nitrites. Consequently, a non-targeted metabolomic analysis using LC-MS was conducted to identify 342 significantly different metabolites between L. plantarum A50 and MRS broth. Among these, lipids and lipid-like molecules, organic acids and derivatives, organic oxygen compounds, and organoheterocyclic compounds emerged as the main constituents. Lipids and lipid-like molecules, derivatives of glucose and galactose, amino acids and their derivatives, as well as organoheterocyclic compounds, are likely to play a role in nitrite elimination. Through the enrichment analysis of differential metabolic pathways using KEGG, nine distinct pathways were identified. These pathways provide essential nutrients, maintain cellular structure and function, participate in substance transport, regulate metabolic activities, and enhance resistance against pathogenic microorganisms in L. plantarum A50.

A renal clearable fluorogenic probe for in vivo β-galactosidase activity detection during aging and senolysis

Accumulation of senescent cells with age leads to tissue dysfunction and related diseases. Their detection in vivo still constitutes a challenge in aging research. We describe the generation of a fluorogenic probe (sulfonic-Cy7Gal) based on a galactose derivative, to serve as substrate for β-galactosidase, conjugated to a Cy7 fluorophore modified with sulfonic groups to enhance its ability to diffuse. When administered to male or female mice, β-galactosidase cleaves the O-glycosidic bond, releasing the fluorophore that is ultimately excreted by the kidneys and can be measured in urine. The intensity of the recovered fluorophore reliably reflects an experimentally controlled load of cellular senescence and correlates with age-associated anxiety during aging and senolytic treatment. Interestingly, our findings with the probe indicate that the effects of senolysis are temporary if the treatment is discontinued. Our strategy may serve as a basis for developing fluorogenic platforms designed for easy longitudinal monitoring of enzymatic activities in biofluids.

Synthesis of Galactoacrylamide and Study of Stimuli‐Responsive Fluorescent Hierarchical Self‐Assembly‐Promoted Specific Interactions with Proteins

AbstractA new sugar based acrylamide, 6‐N‐acrylamido‐D‐galactopyranose (Gal‐acryl) was synthesized from D‐galactose in 6 steps. A solution of Gal‐acryl at basic pH exhibited concentration dependent fractal type assembly formation upon solvent evaporation as revealed by the microscopic images. The fractal dimensions calculated point towards Diffusion Limited Aggregation mode of aggregate formation. The critical aggregation concentration (CAC) of Gal‐acryl in water was found to be 49.3 μM. The increase in fluorescence intensity accompanied by blue shift in emission maxima of coumarin 153 suggests increase in non‐polar environment with Gal‐acryl concentration. The I1/I3ratio of pyrene emission confirmed more non‐polar microenvironment at acidic pH and vice versa at basic pH. Self‐assembly allows Gal‐acryl to exhibit specificity to lectin RCA120 as is demonstrated by fluorescence study further supported by turbidimetric assay. The fluorescence quenching studies with FITC‐RCA120 afforded the Ka value as 6.34×105 M−1, which is much higher than Ka values observed for small galactose derivatives. The present study may help in designing different fractal like glycomaterials with potential applications in drug delivery, bio‐sensing, tissue engineering, and as ligands to asialoglycoprotein receptors that are exclusively expressed by liver cells.

Synthesis of a Series of Trimeric Branched Glycoconjugates and Their Applications for Supramolecular Gels and Catalysis.

Carbohydrate-derived molecular gelators have found many practical applications as soft materials. To better understand the structure and molecular gelation relationship and further explore the applications of sugar-based gelators, we designed and synthesized eight trimeric branched sugar triazole derivatives and studied their self-assembling properties. These included glucose, glucosamine, galactose, and maltose derivatives. Interestingly, the gelation properties of these compounds exhibited correlations with the peripheral sugar structures. The maltose derivative did not form gels in the tested solvents, but all other compounds exhibited gelation properties in at least one of the solvents. Glucose derivatives showed superior performance, followed by glucosamine derivatives. They typically formed gels in toluene and alcohols; some formed gels in ethanol-water mixtures or DMSO water mixtures. The glycoclusters 9 and 10 demonstrated rate acceleration for the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions. These were further studied for their metallogels formation properties, and the copper metallogels from compound 9 were successfully utilized to catalyze click reactions. These metallogels were able to form a gel column, which was effective in converting the reactants into the triazole products in multiple cycles. Moreover, the same gel column was used to transform a second click reaction using different reactants. The synthesis and characterization of these compounds and their applications for catalytic reactions were discussed.

Evolutionary Adaptation of Genes Involved in Galactose Derivatives Metabolism in Oil-Tea Specialized Andrena Species.

Oil-tea (Camellia oleifera) is a woody oil crop whose nectar includes galactose derivatives that are toxic to honey bees. Interestingly, some mining bees of the genus Andrena can entirely live on the nectar (and pollen) of oil-tea and are able to metabolize these galactose derivatives. We present the first next-generation genomes for five and one Andrena species that are, respectively, specialized and non-specialized oil-tea pollinators and, combining these with the published genomes of six other Andrena species which did not visit oil-tea, we performed molecular evolution analyses on the genes involved in the metabolizing of galactose derivatives. The six genes (NAGA, NAGA-like, galM, galK, galT, and galE) involved in galactose derivatives metabolism were identified in the five oil-tea specialized species, but only five (with the exception of NAGA-like) were discovered in the other Andrena species. Molecular evolution analyses revealed that NAGA-like, galK, and galT in oil-tea specialized species appeared under positive selection. RNASeq analyses showed that NAGA-like, galK, and galT were significantly up-regulated in the specialized pollinator Andrena camellia compared to the non-specialized pollinator Andrena chekiangensis. Our study demonstrated that the genes NAGA-like, galK, and galT have played an important role in the evolutionary adaptation of the oil-tea specialized Andrena species.

Galactose-functionalized methacrylate polymers as affinity sorbents for extraction of food allergen lectins

In this study, glycidyl methacrylate (GMA)-based materials functionalized with different galactose derivatives were prepared to be used as affinity sorbents for solid-phase extraction (SPE) of several food allergen lectins (such as phytohemagglutinin (PHA)). First, GMA-based polymers were synthesized and then galactose derivatives were immobilized onto the GMA surface using two different synthetic routes. In the first approach, the bare polymer was modified with ethylenediamine and glutaraldehyde, and subsequently two galactose derivatives were immobilized. In the second strategy, the starting polymer was modified with cystamine and gold nanoparticles (AuNPs), on which a thiolated galactose derivative was subsequently anchored. The resulting materials were characterized by scanning electron microscopy and used as SPE sorbents for the isolation of PHA (as probe protein) from food matrices. Different SPE parameters (sample pH, eluent solution composition, binding capacity, sample volume, selectivity and reusability) were evaluated. The material that provided the best PHA recovery (98%) was the one obtained in the second approach, being this material successfully applied to the selective extraction of PHA and other similar lectins from different foods (red and lima dried beans, fresh soybeans and biscuits containing soybean protein traces as indicated in their label). After SDS-PAGE of eluates, all samples only exhibited the characteristic PHA band around 30 kDa, suggesting the high potential of the developed material for application in food allergy field.

ROS-responsive Galactosylated-nanoparticles with Doxorubicin Entrapment for Triple Negative Breast Cancer Therapy.

Triple negative breast cancer (TNBC) is one of the most aggressive tumors with high metastasis and mortality, which constitutes 15~20% of all breast cancers. Chemotherapy remains main therapeutic option in the treatment of patients with TNBC. We developed reactive oxygen species (ROS)-responsive galactosylated nanoparticles (DOX@NPs) as an efficiently targeted carrier for doxorubicin (DOX) delivery to inhibit the growth of TNBC in vitro and in vivo. DOX@NPs were composed of polyacrylate galactose and phenylboronic derivatives conjugation. The in vitro cytotoxicity, cellular uptake, cell apoptosis and cycle distribution of tumor cells treated with different formulations were investigated. Meanwhile in vivo biodistribution and antitumor effects were investigated in a 4T1 tumor-bearing mouse model. DOX@NPs showed good ROS responsiveness and rapid DOX release in the presence of H2O2. Furthermore, our data suggested that DOX@NPs could effectively trigger tumor cells apoptosis and cycle arrest, efficiently accumulate into tumor sites, and suppress tumor growth without adverse side effects. Our results suggested DOX@NP with potent potential as a promising nanocarrier for TNBC therapy, which deserved further investigation for other cancer treatment.

Probing the Importance of Host Symmetry on Carbohydrate Recognition.

The design of molecular cages with low symmetry could allow for more specific tuning of their properties and better mimic the unsymmetrical and complex environment of protein pockets. However, the added value of lowering symmetry of molecular receptors has been rarely demonstrated. Herein, C3 - and C1 -symmetrical cages, presenting the same recognition sites, have been synthesized and investigated as hosts for carbohydrate recognition. Structurally related derivatives of glucose, galactose and mannose were found to have greater affinity to the receptor with the lowest symmetry than to their C3 -symmetrical analogue. According to the host cavity modelling, the C1 symmetry receptor exhibits a wider opening than its C3 -symmetrical counterpart, providing easier access and thus promoting guest proximity to binding sites. Moreover, our results show the high stereo- and substrate selectivity of the C1 symmetry cage with respect to its C3 counterpart in the recognition of sugars.

Benzo[c][1,2]thiazine‐Based Analogs in the Inverse Electron Demand [4+2] Hetero Diels‐Alder Reaction with Glycals: Access to Tetracyclic Fused Galactose and Fucose Derivatives

AbstractThe synthesis and reactivity in an [4+2] inverse electron demand hetero Diels‐Alder reaction (ihDA) of an original class of electron‐poor heterodienes, the N‐substituted‐1H‐benzo[c][1,2]thiazin‐4‐one‐2,2‐dioxides, are described. These are highly reactive electrophiles that allow easy access to unprecedented benzo‐thiazine glyco‐fused derivatives in a remarkably selective way, even when using acetylated glycals, previously unexplored within this version of ihDA. DFT calculations support the experimental data, and moreover show that acetylated dienophiles can easily react making cycloadditions feasible.

The crystal structure of Cry78Aa from Bacillus thuringiensis provides insights into its insecticidal activity

Genetically modified plants with insecticidal proteins from Bacillus thuringiensis (Bt) have been successfully utilized to control various kinds of pests in crop production and reduce the abuse of pesticides. However, a limited number of genes are available for the protection of crops from rice planthopper. Recently, Cry78Aa protein from Bt strain C9F1 has been found to have high insecticidal activity against Laodelphax striatellus and Nilaparvata lugens. It is the first reported single-component protein in the world to combat rice planthoppers, making it very promising for use in transgenic crops. The ambiguous mechanism of Cry78Aa functions prevented further engineering or application. Here, we report the crystal structure of Cry78Aa, which consists of two domains: a C-terminal β-pore forming domain belonging to the aerolysin family and an N-terminal trefoil domain resembling the S-type ricin B lectin. Thus, Cry78Aa could represent a distinctive type of β-pore forming toxin. We also found that Cry78Aa binds carbohydrates such as galactose derivatives and is essential for insecticidal activity against Laodelphax striatellus. Our results suggest a mechanism underlying the function of Cry78Aa against rice planthoppers and pave the way to maximizing the usage of the toxin.

Borane- and Silylium-Catalyzed Difunctionalization of Carbohydrates: 3,6-Anhydrosugar Enabled 1,6-Site Selectivity.

A novel diastereoselective, Lewis acid catalyzed 1,6-difunctionalization of galactose and mannose derivatives has been developed in one pot, via sequential nucleophile additions. Our studies point to the formation of a 3,6-anhydrosugar intermediate as key to the 1,6-site-selectivity. Starting material-specific reactivity occurs when competitive ring-opening C-O cleavage is possible, owed to basicity and stereoelectronic stabilization differences. Lastly, Mayr nucleophilicity parameter values helped predict which reaction conditions would be most suitable for specific nucleophiles.

Pillar[5]arene based glyco-targeting nitric oxide nanogenerator for hyperthermia-induced triple-mode cancer therapy

Nitric oxide (NO)-mediated gas therapy (GT) and alkyl radical (R•) therapy (ART) are emerging cancer therapy modes, and multi-mode therapy has been recognized as an attractive strategy for enhancing anti-cancer efficacy. In this work, a thermal-responsive R• initiator 2,2′-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIBI)-loaded glycol-targeting NO nanogenerator was constructed by first the covalent conjugation of thermal-responsive NO donor of S-nitrosothiols (RSNO) on the surface of mesoporous silica-coated gold nanorods (AuNRs@MSN), then the coating of a supramolecular complex of amino pillar[5]arene (NP5) and galactose derivative (G), and finally the loading of AIBI. The glycol-targeting NO nanogenerator demonstrated specific targeting ability to HepG2 cells owing to the recognition between galactose residues and asialoglycoprotein receptors (ASGPR). Specially, upon 808 nm near-infrared (NIR) irradiation, the AIBI-loaded NO nanogenerator generated hyperthermia to achieve photothermal therapy (PTT), and further GT and ART resulted from the thermal responsiveness of RSNO and AIBI, respectively. In vitro experiments revealed that the AIBI-loaded glyco-targeting NO nanogenerator had good biocompatibility and exhibited effective inhibition to the proliferation of HepG2 cells. This work provides a novel way to supramolecular hybrid drug delivery systems for triple-mode targeting therapy of PTT/GT/ART.

Preparation and Characterization of a Liver Targeted, Poly(amidoamine) Based, Gene Delivery System.

Nonalcoholic steatohepatitis (NASH) is an aggressive liver disease that is considered a major cause of liver cirrhosis and hepatocellular carcinoma. NASH is characterized by multiple underlying genetic mutations, with no approved cure to date. Gene therapies that target those genetic mutations may play a major role in treating this disease, once delivered specifically to the hepatocytes. In this chapter we present, in detail, the synthesis and the characterization of an efficient gene delivery system capable of targeting hepatocytes by exploiting the overexpression of asialoglycoprotein receptors on their cell surface. The targeting ligand, galactose derivative, lactobionic acid (Gal), is first conjugated to bifunctional poly(ethylene glycol) (PEG), and then the formed PEG-Gal is further conjugated to the positively charged polymer, poly(amidoamine) (PAMAM) to form a PAMAM-PEG-Gal construct that can complex and deliver genetic material (e.g., pDNA, siRNA, mRNA) specifically to hepatocytes. We first synthesize PAMAM-PEG-Gal using carbodiimide click chemistry. The synthesized conjugate is characterized using 1H NMR spectroscopy and mass spectrometry. Next, nanoplexes are prepared by combining the positively charged conjugate and the negatively charged genetic material at different nitrogen to phosphate (N/P) ratios; then the size, charge, electrophoretic mobility, and surface morphology of those nanoplexes are estimated. The simplicity of complexing our conjugate with any type of genetic material, the ability of our delivery system to overcome the current limitations of delivering naked genetic material, and the efficiency of delivering its payload specifically to hepatocytes, makes our formulation a promising tool to treat any type of genetic abnormality that arises in hepatocytes, and specifically NASH.

A Novel C1q Domain-Containing Protein Isolated from the Mollusk Modiolus kurilensis Recognizing Glycans Enriched with Acidic Galactans and Mannans.

C1q domain-containing (C1qDC) proteins are a group of biopolymers involved in immune response as pattern recognition receptors (PRRs) in a lectin-like manner. A new protein MkC1qDC from the hemolymph plasma of Modiolus kurilensis bivalve mollusk widespread in the Northwest Pacific was purified. The isolation procedure included ammonium sulfate precipitation followed by affinity chromatography on pectin-Sepharose. The full-length MkC1qDC sequence was assembled using de novo mass-spectrometry peptide sequencing complemented with N-terminal Edman’s degradation, and included 176 amino acid residues with molecular mass of 19 kDa displaying high homology to bivalve C1qDC proteins. MkC1qDC demonstrated antibacterial properties against Gram-negative and Gram-positive strains. MkC1qDC binds to a number of saccharides in Ca2+-dependent manner which characterized by structural meta-similarity in acidic group enrichment of galactose and mannose derivatives incorporated in diversified molecular species of glycans. Alginate, κ-carrageenan, fucoidan, and pectin were found to be highly effective inhibitors of MkC1qDC activity. Yeast mannan, lipopolysaccharide (LPS), peptidoglycan (PGN) and mucin showed an inhibitory effect at concentrations three orders of magnitude greater than for the most effective saccharides. MkC1qDC localized to the mussel hemal system and interstitial compartment. Intriguingly, MkC1qDC was found to suppress proliferation of human adenocarcinoma HeLa cells in a dose-dependent manner, indicating to the biomedical potential of MkC1qDC protein.

Biochemical investigation of an N-acetyltransferase from Helicobacter pullorum.

N-acetylated sugars are often found, for example, on the lipopolysaccharides of Gram-negative bacteria, on the S-layers of Gram-positive bacteria, and on the capsular polysaccharides. Key enzymes involved in their biosynthesis are the sugar N-acetyltransferases. Here, we describe a structural and functional analysis of one such enzyme from Helicobacter pullorum, an emerging pathogen that may be associated with gastroenteritis and gallbladder and liver diseases. For this analysis, the gene BA919-RS02330 putatively encoding an N-acetyltransferase was cloned, and the corresponding protein was expressed and purified. A kinetic analysis demonstrated that the enzyme utilizes dTDP-3-amino-3,6-dideoxy-d-glucose as a substrate as well as dTDP-3-amino-3,6-dideoxy-d-galactose, albeit at a reduced rate. In addition to this kinetic analysis, a similar enzyme from Helicobacter bilis was cloned and expressed, and its kinetic parameters were determined. Seven X-ray crystallographic structures of various complexes of the H. pullorum wild-type enzyme (or the C80T variant) were determined to resolutions of 1.7Å or higher. The overall molecular architecture of the H. pullorum N-acetyltransferase places it into the Class II left-handed-β-helix superfamily (LβH). Taken together, the data presented herein suggest that 3-acetamido-3,6-dideoxy-d-glucose (or the galactose derivative) is found on either the H. pullorum O-antigen or in another of its complex glycoconjugates. A BLAST search suggests that more than 50 non-pylori Helicobacter spp. have genes encoding N-acetyltransferases. Given that there is little information concerning the complex glycans in non-pylori Helicobacter spp. and considering their zoonotic potential, our results provide new biochemical insight into these pathogens.

Synthesis and Self-Assembling Properties of Peracetylated β-1-Triazolyl Alkyl D-Glucosides and D-Galactosides

Carbohydrate-based low-molecular-weight gelators (LMWGs) are useful classes of compounds due to their numerous applications. Among sugar-based LMWGs, certain peracetylated sugar beta-triazole derivatives were found to be effective organogelators and showed interesting self-assembling properties. To further understand the structural influence towards molecular assemblies and obtain new functional materials with interesting properties, we designed and synthesized a library of tetraacetyl beta-1-triazolyl alkyl-D-glucosides and D-galactosides, in which a two or three carbon spacer is inserted between the anomeric position and the triazole moiety. A series of 16 glucose derivatives and 14 galactose derivatives were synthesized and analyzed. The self-assembling properties of these new triazole containing glycoconjugates in different solvents were analyzed. Several glucose derivatives were found to be effective LMWGs, with compound 7a forming gels in a variety of organic solvents as well as in the presence of metal ions in aqueous solutions. The organogels formed by several compounds were characterized using optical microscopy, atomic force microscopy (AFM) and UV-vis spectroscopy, etc. The co-gels formed by compound 7a with the Fmoc derivative 7i showed interesting fluorescence enhancement upon gelation. Several gelators were also characterized using powder X-ray diffraction and FT-IR spectroscopy. The potential applications of these sugar-based gelators for drug delivery and dye removal were also studied.

The Bay Leaves Active Compounds and Its Lipid Oxidative Inhibition Activity in Bulk Cooking Oil

Cooking oil is one of the basic human needs. Improving the quality of bulk cooking oil is necessary because it is related to economic reason. The bulk cooking oil have a lower price than brand package oil, of course. Based on these reasons, research is needed on the use of antioxidants to improve the quality of bulk cooking oil. This study aims to identify the phytochemicals of bay leaves extract through TOF profiling, analysis of iodine number and acid number of bay leaves extract against bulk cooking oil. TOF profiling was carried out to see whether bay leaves had chemical compounds that supported antioxidant activity which had an impact on the inhibition of fat oxidation. The research consisted of 4 stages: 1) extraction and fractionation of bay leaves, 2) TOF profiling of bay leaves extract, 3) application of bay leaves extract to bulk cooking oil, 4) analysis of iodine and acid numbers. Profiling TOF of the bay leaves extract showed 3 peaks : C6H13NO5 (cyclohexanol, galactose, and fructose derivatives), C11H14O5 (pyran and furan), andC11H19NO3 (morpholine derivate). According to SNI, the acid value maximum 0.6 mg KOH/g. Iodine value minimum is 45 g I2/ 100 mL (SNI 3741 : 2013). Based of this data standart, this study recommended use bay leaves extract in concentration 0.80%. The addition of bay leaves extract as much as 0.80% showed an iodine number of 48.2 g I2/100 mL and an acid number of 0.34 mg KOH/g where the positive control TBHQ showed an iodine number of 48.7 g I2/100 mL and an acid number of 0.19 mg KOH/g.

Synthesis and Biological Studies of O3‐Aryl Galactosides as Galectin Inhibitors

Abstractβ‐Galactose derivatives have recently been reported to selectively inhibit galectin‐3, and a library of O3‐arylated galactosides with varying substitution patterns was designed to study such inhibitions further. The O3‐arylated galactosides were synthesized using diaryliodonium salts under mild and transition metal free conditions, providing the target products in moderate to good yields. An O3‐trifluoroethylated galactoside was also synthesized using iodonium salt chemistry. Azido‐substituted products were subsequently transformed into the corresponding triazoles. After deprotection, a selection of galactoside derivatives were evaluated for inhibitory potencies against galectins‐1, 3, 4 N (N‐terminal domain), 4 C (C‐terminal domain), 7, 8 N, 8 C, 9 N, and 9 C and one compound with promising affinity and selectivity for both the N‐ and C‐terminal domain of galectin‐9 was discovered.

Exploring glycosyl sulphates as donors for chemical glycosylation.

The preparation of anomeric tetrabutylammonium sulphates of glucose and galactose derivatives is reported and their role as donors in glycosylation reactions is studied. Metal triflates showed good performance in activating sulphate as a leaving group. Among them, ytterbium triflate in stoichiometric amounts gave the best results. Basic conditions using barium oxide in combination with trimethylsilyl trifluoromethanesulfonate (TMSOTf) were also shown to give good results. Benzylated sulphates were much more reactive than benzoylated donors when activated either by ytterbium triflate or by BaO and TMSOTf. Different acceptors were tested, such as isopropanol, cholesterol, and other common sugar derivatives. High reaction rates and excellent glycosylation yields were obtained under mild reaction conditions. The α/β anomeric ratio suggests a predominant SN2-like reaction mechanism.