Electronically varied quinazolinaps for asymmetric catalysis

The synthesis and resolution of electronically varied axially chiral Quinazolinaps is reported. These ligands bear different aryl groups on the donor phosphorus atom and were synthesised as part of our investigations into electronic effects within this ligand class. A diastereomerically pure palladacycle of one ligand was characterised by X-ray crystallography. The application of these Quinazolinaps to the rhodium-catalysed hydroboration of vinylarenes resulted in enantioselectivities of up to 92%. Their application to the palladium-catalysed allylic alkylation of 1,3-diphenylprop-2-enyl acetate resulted in conversions of up to 99% and enantioselectivities of up to 94%.     

Structure, formation and catalytic studies of a meso-palladioporphyrin intermediate in a Heck reaction

A meso-palladioporphyrin intermediate was isolated from a Heck reaction between an iodoporphyrin and a non-activated olefin using a Pd(PPh3)2Cl2/Et3N system; its structure was characterized by NMR, MS and X-ray crystallography. Studies on its formation indicate that the Pd(II) catalyst was reduced in situ by Et3N with the assistance of water. The catalytic activity of the intermediate was confirmed by stoichiometric and catalytic reactions using a more reactive olefin, ethyl acrylate.     

A stereodivergent synthesis of beta-hydroxy-alpha-methylene lactones via vinyl epoxides

A catalytic diastereoselective sulfonium ylide epoxidation of aldehydes furnished original vinyl epoxides, having an MBH backbone. These highly functionalized building blocks were used for a formal synthesis of the antibiotic conocandin, and opened up a stereodivergent route towards beta-hydroxy-alpha-methylene lactones, core units of naturally occurring compounds. Under acidic conditions, the oxiranes were mainly transformed, with moderate to good yields, into trans beta-hydroxy-alpha-methylene lactones. On the other hand, a user-friendly palladium-catalysed CO2 insertion and cyclisation sequence gave the cis beta-hydroxy-alpha-methylene lactone counterparts along with an interesting cis-trans equilibration of the pi-allyl intermediates.     

A New Sulfur‐containing Schiff‐Base Ligand and Binding to Copper(II) and Cobalt(II)

A new Schiff‐base ligand having a potentially coordinating thioether group (2‐quinoline‐N‐(2′‐methylthiophenyl)methyleneimine, qmtpm ) has been prepared. The synthesis, structure, UV‐Vis and EPR studies of one copper(II) and two cobalt(II) complexes from this ligand is reported. The X‐ray structures of the Cu^II and Co^II chlorido complexes 1 and 2 reveal the metal atoms in highly distorted square‐pyramidal environments constituted of one tridentate ligand and two anions. On the other hand, the thiocyanato Co^II compound 3 exhibits a distorted trigonal‐bipyramidal structure. These structural variations are apparently due to the different counter‐ions which leads to distinct lattice interactions. The spectroscopic data obtained by EPR and UV‐Vis investigations are in agreement with the solid‐state structures of the coordination compounds.     

Quantitative multiresidue method for about 100 veterinary drugs in different meat matrices by sub 2-microm particulate high-performance liquid chromatography coupled to time of flight mass spectrometry

A quantitative multiresidue method covering more than 100 veterinary drugs, belonging to different drug families, has been developed. The proposed approach uses an liquid-liquid-solid extraction technique (bi-polarity extraction) which is capable in recovering polar, medium polar and apolar compounds. A thorough generic reversed phase solid-phase extraction (SPE) clean-up removes interfering proteins and provides clean and stable extracts. Dedicated rinsing steps are proposed to reduce analyte adsorption on glass walls and on precipitating proteins. The resulting extract is analyzed by ultra-performance liquid chromatography (UPLC) coupled to time of flight mass spectrometry (TOF). The method was validated according to the Commission Decision 2002/657/EEC. Validation coved the relevant meat matrices (muscle, kidney and liver).     

ZrCl4 as an efficient catalyst for a novel one-pot protection/deprotection synthetic methodology

A catalytic quantity of ZrCl 4 (20 mol %) was found to be an efficient catalyst for the one-pot esterification and deprotection of (5 S,6 R)-5,6-diacetoxyoct-7-enoic acid in good yields (44-62%) with a lactone formed as a minor byproduct. ZrCl 4 (10-20 mol %) was also sufficient to deprotect 1,3-dioxalane, bis-TBDMS ethers, and diacetate functional groups in excellent yields of up to 93%. ZrCl 4 (1-10 mol %) also promoted diol protection as the acetonide in 90% yield and acted as a trans-esterification catalyst for a range of esters.     

Solubilizing mutations used to crystallize one CFTR domain attenuate the trafficking and channel defects caused by the major cystic fibrosis mutation

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) Cl(-) channel. F508del, the most frequent CF-causing mutation, disrupts both the processing and function of CFTR. Recently, the crystal structure of the first nucleotide-binding domain of CFTR bearing F508del (F508del-NBD1) was elucidated. Although F508del-NBD1 shows only minor conformational changes relative to that of wild-type NBD1, additional mutations (F494N/Q637R or F429S/F494N/Q637R) were required for domain solubility and crystallization. Here we show that these solubilizing mutations in cis with F508del partially rescue the trafficking defect of full-length F508del-CFTR and attenuate its gating defect. We interpret these data to suggest that the solubilizing mutations utilized to facilitate F508del-NBD1 production also assist folding of full-length F508del-CFTR protein. Thus, the available crystal structure of F508del-NBD1 might correspond to a partially corrected conformation of this domain.     

Analysis of native amino acids by liquid chromatography/electrospray ionization mass spectrometry: comparative study between two sources and interfaces

The analytical performances of two triple-quadrupole instruments, which differ in their atmospheric-pressure sources, were evaluated for native amino acid analysis. The Applied Biosystems/Sciex API 300 instrument was equipped with a turboIon Spray source and a curtain gas interface while the Waters/Micromass Quattro Ultima instrument was characterized by its Z-spray source. Liquid chromatography/mass spectrometry analysis of native amino acids requires volatile ion-pairing mobile phase additives (mainly perfluorinated carboxylic acids). The effects of the structure and concentration of the ion-pairing reagents as well as the organic modifier percentage on the electrospray response of amino acids were studied in detail. The most favourable chromatographic conditions depend strongly on the mass spectrometer used. Several instrumental parameters were also studied, including spray voltage, transmission lens voltages, temperature of desolvation and auxiliary gas flow rates. The results show substantial qualitative differences depending on the instrument geometry. The quantitative performances of the two triple-quadrupole mass spectrometers were evaluated in terms of limits of detection and quantification. The effects of the matrix on the analyte ionization were also examined, and the long-term stability of the electrospray performance was studied over 12 h using a mobile phase containing the perfluorinated ion-pairing reagents. The study provides information on the robustness of the MS instrument and its detection sensitivity towards native amino acid analysis. It appears that each instrument has its good and bad points since one provides higher sensitivity while another is more robust.     

Patterns of the ferrocyanide-iodate-sulfite reaction revisited: the role of immobilized carboxylic functions

We experimentally demonstrate that the standing lamella reaction-diffusion patterns initially observed 17 years ago in a gel-filled open spatial reactor operated with the ferrocyanide-iodate-sulfite bistable reaction requires an upper critical concentration of low-mobility species with weak acid functional groups, a parameter that was overlooked at the time and had made observations difficult to reproduce. The present approach enables the control of the space scale separation between activatory and inhibitory processes. It makes the wealth of exotic pattern dynamics observed earlier easier to reproduce and understand. This contribution should considerably revive the interest in this reaction and boost the search for the control of reaction-diffusion patterns in other bistable systems.