A two-step synthesis of aminopropylpiperidines via aminopropargylpyridines, suitable for the synthesis of a new class of 5-HT4 ligands

A rapid and flexible synthetic approach to {[bis(tert-butoxycarbonyl)amino]propyl}piperidines 5 and related compounds is described. The key step is a three-component coupling process of 2-, 3- or 4-bromopyridine, propargyl bromide and potassium di-tert-butyliminodicarbonate under palladium-copper catalysis leading to 2-, 3- or 4-{[bis(tert-butoxycarbonyl)amino]-propargyl}pyridines 4 followed by a catalytic reduction step.     

Improved method to quantify intracellular zidovudine mono- and triphosphate in peripheral blood mononuclear cells by liquid chromatography-tandem mass spectrometry

The determination of intracellular triphosphate metabolites of nucleoside analogs used in anti-HIV therapy is very challenging. Despite the well-known sensitivity and selectivity of LC-MS/MS, the measurement of the triphosphate metabolite of zidovudine (AZT-TP) remains difficult because of the interferences induced by endogenous nucleotides triphosphates. We describe a new approach that allows improved determination of AZT-TP simultaneously with AZT-monophosphate (MP). This was obtained, first, by monitoring a transition from the molecular ion of AZT-TP to a minor but very specific product ion. Then, the spiking of samples with a constant amount of AZT-TP allowed the signal to emerge from background, leading to increased sensitivity. Finally, the analytical run time was reduced to less than 10 min. The low limits of quantification were at 150 and 300 fmol per sample for AZT-TP and AZT-MP, respectively. Recoveries were higher than 85%. Inaccuracy and precision were lower than 10% and 15% (17% at the limit of quantification), respectively. The new method offers the possibility of determining simultaneously other nucleotide phosphates, as shown here for d4T-TP (the triphosphate metabolite of another nucleoside analog, stavudine or d4T) and 2'-deoxythymidine-5'-triphosphate or dTTP (the corresponding natural nucleotide triphosphate).     

Palladate salts from chiral pyridinium ionic liquids: synthesis and crystal structures

This paper reports the preparation, characterization and the crystal X-ray structures of metal-containing ionic liquid complexes based on chiral pyridinium cations and tetrachloropalladate (II) [PdCl4]2-.     

Vesicles in ionic liquids

The formation of vesicles from 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) in several room-temperature ionic liquids, namely, 1-butyl-3-methylimidazolium tetrafluoroborate (BmimBF(4)), 1-butyl-3-methylimidazolium hexafluorophosphate (BmimPF(6)), 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (EmimNTf(2)), and N-benzylpyridinium bis(trifluoromethylsulfonyl)imide (BnPyNTf(2)), as well as in a water/BmimBF(4) mixture, was investigated. In pure ionic liquids, observations by staining transmission electron microscopy demonstrated clearly the formation of spherical structures with diameters of 200-400 nm. The morphological characteristics of these vesicles in ionic liquids, in particular, the membrane thicknesses, were first investigated by small-angle neutron scattering measurements. The mean bilayer thickness was found to be ～63 ± 1 ? in a deuterated ionic liquid (BnPyNTf(2)-d). This value was similar to that observed in water. The effect of ILs on the modification of the phase physical properties of multilamellar vesicles (MLVs) was then investigated by differential scanning calorimetry. In pure IL as in water, DPPC exhibited an endothermic pretransition followed by the main transition. These transition temperatures and the associated enthalpies in ILs were higher than those in water because of a reduction of the electrostatic repulsion between zwitterionic head groups. To better understand the effect of ionic liquid on the formation of multilamellar vesicles, mixtures of BmimBF(4) and water, which are miscible in all proportions, were analyzed (BmimBF(4)/water ratio from 0% to 100%). SANS and DSC experiments demonstrated that the bilayer structure and stability were strongly modified by the IL content. Moreover, matching SANS experiments showed that BmimBF(4) molecules prefer to be located inside the DPPC membrane rather than in water.     

A mixed 3D-Shell analytical model for the prediction of sound transmission through sandwich cylinders

The sound transmission through an infinite multilayer cylinder composed of orthotropic skins and an isotropic polymer core is calculated analytically. The motions of the two thin orthotropic skins are described with the first-order shear deformation theory while the isotropic core is modeled with the three-dimensional elasticity theory. The polymer core transfer matrix relating the displacements and the stresses at the two common interfaces between the core and the skins is first calculated. The coupling of the two skins is then made using the modal transfer matrix of the core, leading to the global dynamic equilibrium of the multilayer cylinder. The sound Transmission Loss (TL) of the cylinder excited by an acoustic plane wave is finally calculated. Our results are compared with results published recently in the literature. Excellent agreement is observed for thin cores where the three layers vibrate in phase in the radial direction. The usefulness of the three-dimensional model is demonstrated for a thick and soft core in the higher frequency domain where the skins are vibrating out of phase with a relative displacement in the radial direction. Finally, a parametric study is conducted to demonstrate the influence of the damping of each layer and some observations are made on the shear and compressional strain energies of each layer.     

Manifold Reconstruction Using Tangential Delaunay Complexes

We give a provably correct algorithm to reconstruct a k-dimensional smooth manifold embedded in d-dimensional Euclidean space. The input to our algorithm is a point sample coming from an unknown manifold. Our approach is based on two main ideas: the notion of tangential Delaunay complex defined in Boissonnat and Flötotto (Comput. Aided Des. 36:161–174, 2004), Flötotto (A coordinate system associated to a point cloud issued from a manifold: definition, properties and applications. Ph.D. thesis, 2003), Freedman (IEEE Trans. Pattern Anal. Mach. Intell. 24(10), 2002), and the technique of sliver removal by weighting the sample points (Cheng et al. in J. ACM 47:883–904, 2000). Differently from previous methods, we do not construct any subdivision of the d-dimensional ambient space. As a result, the running time of our algorithm depends only linearly on the extrinsic dimension d while it depends quadratically on the size of the input sample, and exponentially on the intrinsic dimension k. To the best of our knowledge, this is the first certified algorithm for manifold reconstruction whose complexity depends linearly on the ambient dimension. We also prove that for a dense enough sample the output of our algorithm is isotopic to the manifold and a close geometric approximation of the manifold.     

Iterative multifunctionalization of unactivated C-H bonds in piperidines by way of intramolecular Rh(II)-catalyzed aminations

Efficient stereocontrolled synthesis of di-, tri-, tetra-, and pentasubstituted piperidines from simple 2-sulfamoyloxymethyl piperidine derivatives has been performed by way of intramolecular Rh-catalyzed amination of saturated C-H bonds. In this process, the sulfamoyloxymethyl arm was directly or indirectly involved in the functionalization of every saturated methylene group of the piperidine ring at C-3, C-4, C-5, and C-6. Direct application to the total synthesis of iminosugars and related compounds demonstrated the synthetic potential of this strategy.     

A polyoxometalate-cyanometalate multilayered coordination network

The reaction of the ε-Keggin polyoxometalate (POM) [PMo(12)O(36)(OH)(4){La(H(2)O)(4)}(4)](5+) with Fe(II)(CN)(6)(4-) under typical bench conditions at room temperature and ambient pressure has afforded the novel [ε-PMo(12)O(37)(OH)(3){La(H(2)O)(5)(Fe(CN)(6))(0.25)}(4)] network, which exhibits a three-dimensional multilayered structure. The compound has been fully characterized by synchrotron-radiation X-ray crystallography, IR spectroscopy, elemental analysis, and thermogravimetric analysis. This coordination network constitutes the first example of a cyanometalate bonded to a POM unit.     

Platinum oxide catalyzed silylation of aryl halides with triethylsilane: an efficient synthetic route to functionalized aryltriethylsilanes

[STRUCTURE: SEE TEXT] The first platinum-catalyzed selective silylation of aryl halides including aryl iodides and bromides having an electron-withdrawing group is described. The reaction takes place rapidly in NMP with triethylsilane as a silicon source and sodium acetate to provide functionalized aryltriethylsilanes in moderate to good yields. Heteroaromatic halides also were found to be readily silylated with triethylsilane. The procedure is chemoselective and tolerates a wide variety of functional groups.     

Study of hydrogen bonding in liquid crystalline solvent by Fourier transform infrared spectroscopy

A hydrogen-bonded complex between an aromatic acid and an enantiopure chiral amine has been dissolved in a nematic solvent, giving rise to a cholesteric medium. Fourier transform infrared (FT-IR) experiments have been performed at various temperatures on both sides of the cholesteric-isotropic transition. Liquid crystalline order provides significant enhancement to the strength of interaction, inducing a discontinuous jump in concentration of the complex at the cholesteric-isotropic transition.