A palladium-catalyzed glycosylation reaction: the de novo synthesis of natural and unnatural glycosides

A highly stereoselective and sterospecific palladium-catalyzed glycosylation reaction of a variety of alcohols is reported. The reaction selectively converts alpha-2-substituted 6-carboxy-2H-pyran-3(6H)-ones into alpha-2-substituted 6-alkoxy-2H-pyran-3(6H)-ones with complete retention of configuration and similarly converts the pyranones with beta-carboxy groups into pyranones with beta-alkoxy groups. The reaction works equally well with both amino acid- and carbohydrate-based alcohols. To demonstrate the utility of this process for carbohydrate chemistry several of the products were selectively converted into alpha-manno-pyranosides in two additional steps. Because the 2-substituted 6-carboxy-2H-pyran-3(6H)-ones are prepared by asymmetric synthesis, this reaction can be used for the preparation of either d- or l-pyranones.     

Infinite Dilution Activity Coefficients and Gas-to-Liquid Partition Coefficients of Organic Solutes Dissolved in 1-Benzylpyridinium Bis(Trifluoromethylsulfonyl)Imide and 1-Cyclohexylmethyl-1-Methylpyrrolidinium Bis(Trifluoromethylsulfonyl)Imide

Infinite dilution activity coefficients and gas-to-ionic liquid partition coefficients were measured for a chemically diverse set of 48 or more organic solute probes dissolved in the ionic liquids 1-benzylpyridinium bis(trifluoromethylsulfonyl)imide ([BzPy][Tf₂N]) and 1-cyclohexylmethyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide ([ChxmPyrr][Tf₂N]) in the temperature range from 323.15 to 373.15 K using inverse gas chromatography. Selectivities and capacities for different separation problems were calculated from the measured chromatographic data. The measured partition coefficients were correlated using mathematical equations based on the Abraham general solvation parameter model. The derived Abraham model correlations back-calculated the observed partition coefficients to within 0.12 log₁₀ units.     

Synthesis of novel isoxazole functionalized pyrazolo[3,4-b]pyridine derivatives; their anticancer activity

A series of novel isoxazole functionalized pyrazolo[3,4-b]pyridine derivatives 5a-n were prepared, respectively, initiated from 6-thiophenyl-4-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-3-amine 3 through selective N-propargylation, and these N-propargylated compounds 4 were cyclized with aryloximes by using of sodium hypochlorite, and obtained the title products 5a-n . All the final products 5a-n were submitted for anticancer activity against four cancer cell lines such as “HeLa—cervical cancer (CCL-2); COLO 205—colon cancer (CCL-222); HepG2—liver cancer (HB-8065); MCF7—breast cancer (HTB-22)”; Compounds 5c , 5d , and 5h are found to have more prominent anticancer activity at micro molar concentration.     

Formation of pH‐Resistant Monodispersed Polymer–Lipid Nanodiscs

Polymer lipid nanodiscs are an invaluable system for structural and functional studies of membrane proteins in their near‐native environment. Despite the recent advances in the development and usage of polymer lipid nanodisc systems, lack of control over size and poor tolerance to pH and divalent metal ions are major limitations for further applications. A facile modification of a low‐molecular‐weight styrene maleic acid copolymer is demonstrated to form monodispersed lipid bilayer nanodiscs that show ultra‐stability towards divalent metal ion concentration over a pH range of 2.5 to 10. The macro‐nanodiscs (>20 nm diameter) show magnetic alignment properties that can be exploited for high‐resolution structural studies of membrane proteins and amyloid proteins using solid‐state NMR techniques. The new polymer, SMA‐QA, nanodisc is a robust membrane mimetic tool that offers significant advantages over currently reported nanodisc systems.     

Design,Synthesis, and Anti-Proliferative Activity of Some New Quinoxaline Containing 1,2,4-Thiadiazoles Amide Hybrids

Russian Journal of General Chemistry - A series of new quinoxaline-1,2,4-thiadiazoles amide hybrids has been synthesized and evaluated for their anti-proliferative activity on four different human...     

Design,synthesis, antitubercular and antibacterial activities of pyrrolo[3,2-b]pyridine-3-carboxamide linked 2-methoxypyridine derivatives and in silico docking studies

Abstract

A novel series pyrrolo[3,2-b]pyridine-3-carboxamide linked 2-methoxypyridine derivatives have been designed, synthesized and confirmed by FT-IR, ¹H NMR, ¹³C NMR, ¹⁹F NMR, MS, and elemental analysis. The synthesized compounds were screened for their antitubercular activity using microplate alamar blue assay method and antibacterial activity. Among the tested compounds, 4- fluorophenyl (8m), 4- chlorophenyl (8n) and 4-methoxyphenyl (8i) showed potent anti-TB activity (3.12?µg/mL) in comparison with reference drug, Pyrazinamide ((3.12?µg/mL). In addition, all compounds were docked into DprE1 (PDB code: 4KW5) to explore their binding interactions at the active site. The compounds exhibited essential key interactions as that of reported DprE1 inhibitors and hence, the synthesized compounds may be considered as molecular scaffolds for antitubercular activity. Compounds, 4-chlorophenyl (8n) and 4-flurophenyl (8m) showed significant antibacterial activity against Escherichia coli and Staphylococcus aureus strains. In silico prediction of toxicities, druglikeness and drug score profiles of the tested compounds are promising.     

Estimation of the 2.05 helix type i→i hydrogen bond energy at Aib-Oxa motif: an isodesmic approach

Bending at the valence angle N–C^α–C′ (τ) is a known control feature for attenuating the stability of the rare intramolecular i→i hydrogen bonded pseudo five-membered ring C₅ structures, the so called 2.0₅ helices, at Aib. The competitive 3₁₀-helical structures still predominate over the C₅ structures at Aib for most values of τ. However at Aib^∗, a mimic of Aib where the carbonyl O of Aib is replaced with an imidate N (in 5,6-dihydro-4H-1,3-oxazine = Oxa), in the peptidomimic Piv-Pro-Aib^∗-Oxa (1), the C₅i structure is persistent in both crystals and in solution. Here we show that the i→i hydrogen bond energy is a more determinant control for the relative stability of the C₅ structure and estimate its value to be 18.5 ± 0.7 kJ/mol at Aib^∗ in 1, through the computational isodesmic reaction approach, using two independent sets of theoretical isodesmic reactions.     

Accessing the disallowed conformations of peptides employing amide-to-imidate modification

Selective modification of the C-terminal amide in peptides to dihydrooxazine (a novel stable imidate isostere) by intramolecular nucleophilic cyclo-O-alkylation of the corresponding N-(3-bromopropyl)amides results in constraining of the C-terminal residue in natively disallowed conformations both in crystals and in solution.     

Synthesis,Spectral Characterization,DNA/ Protein Binding,DNA Cleavage,Cytotoxicity, Antioxidative and Molecular Docking Studies of Cu(II)Complexes Containing Schiff Base-bpy/Phen Ligands

Ternary Cu(II) complexes [Cu(II)(L)(bpy)Cl] 1, [Cu(II)(L)(Phen)Cl] 2 [L = 2,3–dimethyl-1-phenyl-4(2 hydroxy-5-methyl benzylideneamino)-pyrazol-5-one, bpy = 2,2^′ bipyridine, phen =1,10 phenanthroline) were synthesized and characterized by elemental analyses, UV-Visible, FT-IR, ESR, Mass, thermogravimetric and SEM EDAX techniques. The complexes exhibit octahedral geometry. The interaction of the Cu(II) with cailf thymus DNA (CT-DNA) was explored by using absorption and fluorescence spectroscopic methods. The results revealed that the complexes have an affinity constant for DNA in the order of 10⁴ M^?1 and mode of interaction is intercalative mode. The DNA cleavage study showed that the complexes cleaved DNA without any external agent. The interaction of Cu(II) complexes with bovine serum albumin (BSA) was also studied using absorption and fluorescence techniques. The cytotoxic activity of the Cu(II) complexes was probed in HeLa (human breast adenocarcinoma cell line), B16F10 (Murine melanoma cell line) and HEPA1–6 celllines, complex 1 has good cytotoxic activity which is comparable with the doxarubicin drug, with IC₅₀ values ranging from 3 to 12.6 μM. A further molecular docking technique was employed to understand the binding of the complexes towards the molecular target DNA. Investigation of the antioxidative properties showed that the metal complexes have significant radical scavenging activity potency against DPPH radical.     

Magnetic Alignment of Polymer Macro‐Nanodiscs Enables Residual‐Dipolar‐Coupling‐Based High‐Resolution Structural Studies by NMR Spectroscopy

Experimentally measured residual dipolar couplings (RDCs) are highly valuable for atomic‐resolution structural and dynamic studies of molecular systems ranging from small molecules to large proteins by solution NMR spectroscopy. Here we demonstrate the first use of magnetic‐alignment behavior of lyotropic liquid‐crystalline polymer macro‐nanodiscs (>20 nm in diameter) as a novel alignment medium for the measurement of RDCs using high‐resolution NMR. The easy preparation of macro‐nanodiscs, their high stability against pH changes and the presence of divalent metal ions, and their high homogeneity make them an efficient tool to investigate a wide range of molecular systems including natural products, proteins, and RNA.