Influence of Selective Deoxyfluorination on the Molecular Structure of Type-2 -Acetyllactosamine.

-Acetyllactosamine is a common saccharide motif found in various biologically active glycans. This motif usually works as a backbone for additional modifications and thus significantly influences glycan conformational behavior and biological activity. In this work, we have investigated the type-2 -acetyllactosamine scaffold using the complete series of its monodeoxyfluorinated analogs.

Synthesis and unexpected binding of monofluorinated N,N'-diacetylchitobiose and LacdiNAc to wheat germ agglutinin.

Fluorination of carbohydrate ligands of lectins is a useful approach to examine their binding profile, improve their metabolic stability and lipophilicity, and convert them into F NMR-active probes. However, monofluorination of monovalent carbohydrate ligands often leads to a decreased or completely lost affinity. By chemical glycosylation, we synthesized the full series of methyl β-glycosides of N,N'-diacetylchitobiose (GlcNAcβ(1-4)GlcNAcβ1-OMe) and LacdiNAc (GalNAcβ(1-4)GlcNAcβ1-OMe) systematically monofluorinated at all hydroxyl positions.

Exploring long-range fluorine-carbon J-coupling for conformational analysis of deoxyfluorinated disaccharides: A combined computational and NMR study.

In this study, we investigated the potential of long-range fluorine-carbon J-coupling for determining the structures of deoxyfluorinated disaccharides. Three disaccharides, previously synthesized as potential galectin inhibitors, exhibited through-space fluorine-carbon J-couplings. In our independent conformational analysis of these disaccharide derivatives, we employed a combination of density functional theory (DFT) calculations and nuclear magnetic resonance (NMR) experiments.

The Effect of Deoxyfluorination on Intermolecular Interactions in the Crystal Structures of 1,6-Anhydro-2,3-epimino-hexopyranoses.

The effect of substitution on intermolecular interactions was investigated in a series of 1,6-anhydro-2,3-epimino-hexopyranoses. The study focused on the qualitative evaluation of intermolecular interactions using DFT calculations and the comparison of molecular arrangements in the crystal lattice. Altogether, ten crystal structures were compared, including two structures of C4-deoxygenated, four C4-deoxyfluorinated and four parent epimino pyranoses.

Selectively Deoxyfluorinated N-Acetyllactosamine Analogues as F NMR Probes to Study Carbohydrate-Galectin Interactions.

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.

Synthesis of multiply fluorinated -acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides.

Multiple fluorination of glycostructures has emerged as an attractive way of modulating their protein affinity, metabolic stability, and lipophilicity. Here we described the synthesis of a series of mono-, di- and trifluorinated -acetyl-ᴅ-glucosamine and ᴅ-galactosamine analogs. The key intermediates are the corresponding multiply fluorinated glucosazide and galactosazide thioglycosides prepared from deoxyfluorinated 1,6-anhydro-2-azido-β-ᴅ-hexopyranose precursors by ring-opening reaction with phenyl trimethylsilyl sulfide.

The effect of deoxyfluorination and -acylation on the cytotoxicity of -acetyl-D-gluco- and D-galactosamine hemiacetals.

Fully acetylated deoxyfluorinated hexosamine analogues and non-fluorinated 3,4,6-tri-O-acylated N-acetyl-hexosamine hemiacetals have previously been shown to display moderate anti-proliferative activity. We prepared a set of deoxyfluorinated GlcNAc and GalNAc hemiacetals that comprised both features: O-acylation at the non-anomeric positions with an acetyl, propionyl and butanoyl group, and deoxyfluorination at selected positions. Determination of the in vitro cytotoxicity towards the MDA-MB-231 breast cancer and HEK-293 cell lines showed that deoxyfluorination enhanced cytotoxicity in most analogues.

Development of α-Selective Glycosylation for the Synthesis of Deoxyfluorinated T Antigen Analogues.

The Tn antigen (GalNAcα1-Thr/Ser) is abundantly expressed in many tumors but rarely found in healthy tissues, which makes it an attractive epitope for antitumor immunotherapy. The use of the Tn antigen in the development of therapeutic antitumor vaccines is hampered by its low immunogenicity, which may be enhanced by deoxyfluorination of the GalNAc moiety. Here, we report the synthesis of protected 3- and 4-fluoro analogues of the threonine-containing Tn antigen.

Use of remote acyl groups for stereoselective 1,2-cis-glycosylation with fluorinated glucosazide thiodonors.

Fluorinated glycans are valuable probes for studying carbohydrate-protein interactions at the atomic level. Glucosamine is a ubiquitous component of glycans, and the stereoselective synthesis of α-linked fluorinated glucosamine is a challenge associated with the chemical synthesis of fluorinated glycans. We found that introducing a 6-O-acyl protecting group onto 3-fluoro and 4-fluoro glucosazide thiodonors endowed them with moderate α-selectivity in the glycosylation of carbohydrate acceptors, which was further improved by adjusting the acceptor reactivity via O-benzoylation.

Synthesis of a Helical Phosphine and a Catalytic Study of Its Palladium Complex.

In this study, 9-(diphenylphosphanyl)[7]helicene was prepared as a suitable ligand for the subsequent synthesis of palladium complexes. The corresponding PdLCl complex was then successfully obtained in both racemic and enantiopure forms. The PdLCl complex emerges exclusively in the arrangement showing dynamic interconversion between its homo- and heterochiral forms as evidenced by P NMR.

Stereoselectivity in Glycosylation with Deoxofluorinated Glucosazide and Galactosazide Thiodonors.

Control of anomeric stereoselectivity in glycosylation with deoxofluorinated glycosyl donors is critical for assembly of fluorinated oligosaccharides. Here, we report the synthesis of benzylated 3-fluoro and 4-fluoro analogues of phenyl 1-thioglucosazide and galactosazide donors and evaluation of their stereoselectivity in glycosylation of a series of model carbohydrate acceptors using the TfO/PhSO promoter system. Low-temperature NMR revealed formation of covalent α-triflate and both anomers of oxosulfonium triflates under selected glycosylation conditions.

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine.

Background: Derivatives of D-glucosamine and D-galactosamine represent an important family of the cell surface glycan components and their fluorinated analogs found use as metabolic inhibitors of complex glycan biosynthesis, or as probes for the study of protein-carbohydrate interactions. This work is focused on the synthesis of acetylated 3-deoxy-3-fluoro, 4-deoxy-4-fluoro and 3,4-dideoxy-3,4-difluoro analogs of D-glucosamine and D-galactosamine via 1,6-anhydrohexopyranose chemistry. Moreover, the cytotoxicity of the target compounds towards selected cancer cells is determined.

A comprehensive LC/MS analysis of novel cyclopentenedione library.

Cyclopentenediones (CPDs) are compounds with a variety of applications ranging from the preparation of functional polymers to the development of antimicrobial agents, suggesting the potential use of CPDs as novel bioactive compounds or drugs. For this reason, a detailed characterization of CPDs and the development of robust analytical methods for their trace analysis are being sought. Here we focused on the design and synthesis of a library of novelized benzylidene CPD derivatives that were consequently characterized by ultra-high performance liquid chromatography (UHPLC) on-line connected with tandem mass spectrometry (MS/MS).

Evaluation of cytotoxic activity of titanocene difluorides and determination of their mechanism of action in ovarian cancer cells.

Background: Ovarian cancer is the seventh-most common cancer amongst women and the most deadly gynecologic cancer. Cisplatin based drugs are used in first line therapy, but resistance represents a major obstacle for successful treatment. In this study, we investigated the anticancer effects and mechanism of action of three titanocene difluorides, two bearing a pendant carbohydrate moiety (α-D-ribofuranos-5-yl) on their periphery and one without any substitution.

The effect of transient operations on the levels and congener profiles of PCBz, PCPh and PCDD/F in raw flue gases of MSWI plant.

The concentrations and congener profiles of polychlorinated benzenes, phenols, dibenzo-p-dioxin and dibenzofurans, measured in raw flue gases of a real MSWI plant, are discussed in this paper. The data covers steady-state and transient operation conditions, including the memory effect period close to two shutdowns. The highest levels of concentrations of the pollutants were observed the first day after the shutdown with subsequent gradual decrease towards steady-state values.

LC-NMR Technique in the Analysis of Phytosterols in Natural Extracts.

The ability of LC-NMR to detect simultaneously free and conjugated phytosterols in natural extracts was tested. The advantages and disadvantages of a gradient HPLC-NMR method were compared to the fast composition screening using SEC-NMR method. Fractions of free and conjugated phytosterols were isolated and analyzed by isocratic HPLC-NMR methods.

Skeletal rearrangements resulting from reactions of 1,6:2,3- and 1,6:3,4-dianhydro-β-D-hexopyranoses with diethylaminosulphur trifluoride.

A complete series of eight 1,6:2,3- and 1,6:3,4-dianhydro-β-D-hexopyranoses were subjected to fluorination with DAST. The 1,6:3,4-dianhydropyranoses yielded solely products of skeletal rearrangement resulting from migration of the tetrahydropyran oxygen (educts of D-altro and D-talo configuration) or of the 1,6-anhydro bridge oxygen (D-allo, D-galacto). The major products yielded by the 1,6:2,3-dianhydropyranoses were compounds arising from nucleophilic substitution, with configuration at C4 either retained (D-talo, D-gulo) or inverted (D-manno), or from C6 migration (D-allo).

Synthesis of all configurational isomers of 1,6-anhydro-2,3,4-trideoxy-2,3-epimino-4-fluoro-beta-d-hexopyranoses.

We have prepared a full series of 1,6-anhydro-2,3,4-trideoxy-4-fluoro-2,3-epimino-beta-d-hexopyranoses. The key step was the reaction of azido sulfonates possessing a free C-4 hydroxyl with DAST and subsequent LiAlH(4) reduction. Nucleophilic displacement of the hydroxyl activated by DAST proceeded without rearrangement and with moderate to good yields.

Synthesis of 2-aza[6]helicene and attempts to synthesize 2,14-diaza[6]helicene utilizing metal-catalyzed cycloisomerization.

A modular synthetic approach leading to 2-aza[6]helicene is reported. It involves assembly of key hetero biphenylylnaphthalenes from functionalized building blocks and study of their metal catalyzed cycloisomerization.

Synthesis of hexahelicene and 1-methoxyhexahelicene via cycloisomerization of biphenylyl-naphthalene derivatives.

The new approach provides nonphotochemical syntheses of helicenes based on the easy, convergent, and modular assembly of key biphenylyl-naphthalenes and their platinum-catalyzed double cycloisomerization. This sequence of reactions provides a synthetic route to helicenes in two steps from simply accessible building blocks. Furthermore, the method enables the introduction of substituents into the hexahelicene skeleton.

Molecular structure of eight possible configurational isomers of 2,3- and 3,4-epimino derivatives of 1,6-anhydro-β-D-hexopyranoses: conformation analysis, intra- and inter-molecular hydrogen bonds.

The crystal structures of a complete series of configurational isomers of 2,3-epimino and 3,4-epimino derivatives of 1,6-anhydro-β-D-hexopyranoses were determined by single-crystal X-ray analysis. The structures exhibited conformational rigidity within the series regardless of the position and orientation of the aziridine ring. Possible formation of intramolecular hydrogen bonds involving the NH group is discussed with respect to the results of IR spectroscopy and to the intermolecular hydrogen bonds found in the crystal packing.

Matrix effects on the de novo synthesis of polychlorinated dibenzo-p-dioxins, dibenzofurans, biphenyls and benzenes.

The formation of polychlorinated dibenzo-p-dioxins, dibenzofurans, biphenyls and benzenes in de novo synthesis experiments have been studied on model fly ashes with a wide range of matrices. The model fly ash consisted of 18 selected matrices with the addition of CuCl(2) x 2H(2)O, activated charcoal and NaCl. The studied matrices were not restricted to the commonly investigated matrices with defined chemical composition (silica gel, alumina, florisil) and industrially produced adsorbents with silicate structures (diatomaceous earths), but also included natural occurring matrices (clays, kaolin, bentonite and feldspars).

Preparation of N-nosyl-3,4-epimines derived from levoglucosan by sodium borohydride reduction.

Starting from 1,6-anhydro-beta-d-glucopyranose 1 (levoglucosan), N-o-nitrobenzenesulfonyl (nosyl) 3,4-epimino derivatives with d-allo, d-galacto, and d-talo configurations have been prepared via NaBH(4) reduction of suitably substituted azido tosylates. The benefits and limitations of this method over the classical LiAlH(4) reduction method are discussed.