Copper(II) Fluoride a New Efficient Promoter of Chan-Lam-Evans Coupling

The Chan-Lam-Evans coupling is the copper(II) acetate promoted reaction of phenols and boronic acids producing diaryl ethers. In this paper a modification of the original reaction is reported using copper(II) fluoride reagent which gives higher yields than copper(II) acetate. The most significant increase in yield was observed in formation of sterically hindered phenols. We hypothesize that fluoride ions help to cleave the boron-carbon bond. The novel method is suitable for selective, efficient and economical synthesis of diaryl ether compounds under mild conditions

DFT Study of Stereoselective Ketene-imine Cycloadditions, Evaluation of Possible Solvent Effects with IEF-PCM

The formal [2+2] cycloaddition of ketenes and imines, also known as Staudinger synthesis, is a facile method for the synthesis of biologically important β-lactam derivatives. In this paper two previously reported stereoselective reactions were investigated with computational methods. Our computations support experimental data that a chiral imine, derived from d-glyceraldehyde reacting with ketenes, yields almost exclusively one out of the possible four diastereomers. The reaction proceeds stepwise, first addition of the imine to the ketene yields an intermediate, then the product is formed in a conrotatory electrocyclization. Results indicate that the electrostatic repulsion of the chiral auxiliary group is the main factor of the stereoselectivity, but solvent and substituent effects are not negligible. Calculations were performed at M06-2X/6-31+G** level of theory combined with IEF-PCM solvation, in common solvents such as toluene, THF, dichloromethane, acetonitrile and water. These results provide useful insight for the development of new chiral auxiliaries and optimizing reaction parameters

Hypersensitivity to Thromboxane Receptor Mediated Cerebral Vasomotion and CBF Oscillations during Acute NO-Deficiency in Rats

), NO-deficiency is often associated with activation of thromboxane receptors (TP). In the present study we hypothesized that in the absence of NO, overactivation of the TP-receptor mediated cerebrovascular signaling pathway contributes to the development of vasomotion and CBF oscillations. synthesis by ozagrel (10 mg/kg iv.) attenuated it. In isolated MCAs U-46619 in a concentration of 100 nM, which induced weak and stable contraction under physiological conditions, evoked sustained vasomotion in the absence of NO, which effect could be completely reversed by inhibition of Rho-kinase by 10 µM Y-27632.These results suggest that hypersensitivity of the TP-receptor – Rho-kinase signaling pathway contributes to the development of low frequency cerebral vasomotion which may propagate to vasospasm in pathophysiological states associated with NO-deficiency

Experimental and Computational Study on the Debenzylation of (2,4-dimethoxybenzyl)-protected 1,3-diazaoxindoles

The introduction and removal of the 2,4-dimethoxybenzyl (DMB) moiety was studied in order to use it as a protecting group in the synthesis of diverse drug candidates containing the 1,3-diazaoxindole scaffold. The debenzylation of C(5)-unsubstituted and C(5)-isopropylidene-substituted 1,3-diazaoxindoles was investigated under various conditions. The DMB group could only be removed from the latter derivative using triflic acid. This observation can most likely be explained with electronic effects. In order to get a deeper insight into the reaction mechanism, quantum chemical calculations have been performed

Identification and isolation of new neolignan and sesquineolignan species: Their acid-catalyzed ring closure and specific accumulation in the fruit wall of Cirsium eriophorum (L.) Scop.

Abstract In Cirsium eriophorum fruit, the main neolignan and sesquineolignan compounds, denominated prebalanophonin (preBA) and prepicrasmalignan (prePI), were determined for the first time in the plant kingdom using a combination of optimized acid treatments and complementary spectroscopic (HPLC–MS, GC–MS, CD and NMR) methods. Analysis of fruit parts separated via germination, demonstrated the specific accumulation of these compounds, since preBA and prePI were exclusively found in the fruit wall. Based on quantitative approaches obtained by HPLC-UV measurements, the fruit wall was found to contain extraordinarily high amounts of preBA (4.57%) and prePI (2.88%) allowing their high-yield isolation by preparative HPLC. Optimized acidic treatment (2 N trifluoroacetic acid, 50 °C, 15 min) of the wall extract resulted in the quantitative transformation of preBA and prePI into balanophonin (BA) and picrasmalignan (PI), as a result of acid-catalyzed cyclization by the SN2 reaction. Consequently, acid-treated wall extract was found to be the richest raw material containing BA and PI (5.3% and 3.10%), reported to date

Chiral separation of asenapine enantiomers by capillary electrophoresis and characterization of cyclodextrin complexes by NMR spectroscopy, mass spectrometry and molecular modeling

The enantiomers of asenapine maleate (ASN), a novel antipsychotic against schizophrenia and mania with bipolar I disorder have been separated by cyclodextrin (CD) modified capillary zone electrophoresis for the first time. 15 different CDs were screened as complexing agents and chiral selectors, investigating the stability of the inclusion complexes and their enantiodiscriminating capacities. Although initially, none of the applied chiral selectors gave baseline separation, β-CD proved to be the most effective chiral selector. In order to improve resolution, an orthogonal experimental design was employed, altering the concentration of background electrolyte, organic modifier, pH, capillary temperature and applied voltage in a multivariate manner. The developed method (160 mM TRIS-acetate buffer pH 3.5, 7 mM β-CD, at 20 °C, applying 15 kV) was successful for baseline separation of ASN enantiomers (R(s)=2.40±0.04). Our method was validated according to ICH guidelines and proved to be sensitive, linear, accurate and precise for the chiral separation of ASN. Properties of the inclusion complexes, such as stoichiometry, atomic level intermolecular host-guest connections are proposed on the basis of ROESY NMR measurement, ESI-MS spectrometry and molecular modeling studies. It was found that the ASN-β-CD complex is of 1:1 composition, and either of the aromatic rings can be accommodated in the β-CD cavity. Copyright © 2015 Elsevier B.V. All rights reserved

Activation of thromboxane or endothelin receptors induce Rho-kinase dependent vasomotion in NO synthase blocked MCAs.

<p>Quantitative analysis of slow wave oscillations with discrete Fourier transformation in L-NAME treated vessels before and after the administration of the TP-receptor agonist U-46619 (Panel A) or endothelin-1 (Panel B) followed by the Rho-kinase inhibitor Y-27632. Values are mean ± SEM fold changes of the peak magnitudes of the power spectra compared to the baseline. *p<0.05, ***p<0.001 vs. L-NAME, ##<0.01 vs. ET-1 and ###<0.001 vs. U-46619 (n = 10–20).</p

Baseline physiological parameters in the different in vivo experimental groups.

<p>Values are mean ± SEM (n = 7, 10, 6 and 7 in Groups I, IIa., IIb. and IIc., respectively). No significant difference was found between the experimental groups.</p