Cyanide-Free One-Pot Synthesis of Methacrylic Esters from Acetone

Methacrylic esters, represented by methyl methacrylate (MMA), are widely used as commodity chemicals. Here, the one-pot synthesis of methacrylic esters from acetone, a haloform and alcohols in the presence of an organic base is described. Using DBU as the organic base for the reaction of acetone, chloroform and methanol in acetonitrile afforded MMA in 66 % yield. When the solvent was replaced by benzonitrile, the product MMA was successfully purified by distillation. Applicability of this process to various alcohols was also investigated to show ethyl, phenyl, CF₃CH₂, and n-C₆F₁₃CH₂CH₂ esters were obtained in moderate yields. The use of bromoform instead of chloroform resulted in the improvement of the yield, for example, methyl and n-C₆F₁₃CH₂CH₂ esters up to 81 and 70 %, respectively. The reaction with deuterated starting materials acetone-d₆ and MeOH-d₄, with DBU in acetonitrile afforded deuterated MMA (MMA-d₈) in 70 % yield.     

Concise Construction of the ACDE Ring System of Calyciphylline A Type Alkaloids by a [5+2] Cycloaddition

A concise route for construction of the ACDE ring skeleton in calyciphylline A type alkaloids was developed using an intramolecular [5+2] cycloaddition reaction of an oxidopyrylium species bearing a tetrasubstituted olefin. Key to the success of this reaction was the combination of acid and base, which accelerated the construction of this skeleton containing a spiro ring and vicinal quaternary carbon centers. The resultant tricyclic ADE ring compound was converted to an ACDE ring model through C−H oxidation and an aza-Wittig reaction.     

Simultaneous determination of erlotinib and its isomeric major metabolites in human plasma using isocratic liquid chromatography–tandem mass spectrometry and its clinical application

This study developed a method for the simultaneous determination of erlotinib and its isomeric major metabolites, OSI‐413 and OSI‐420, in human plasma using an isocratic liquid chromatography–tandem mass spectrometry. Plasma specimens deproteinized with acetonitrile were separated using a 3‐µm particle size octadecylsilyl column. The m/z values of the precursor and product ions for the analytes were as follows: erlotinib, 394.2/278.2; and OSI‐413 and OSI‐420, 380.2/278.2. The total run time was 21 min and no peaks interfering with the analytes and internal standard (d₆‐erlotinib) in human plasma were observed. The calibration curves of erlotinib, OSI‐413 and OSI‐420 were linear over the concentration ranges of 10–3000, 2–500 and 2–100 ng/mL, respectively. The pretreatment recovery ratios were >86.1%. The intra‐ and inter‐assay precisions and accuracies were <12.7 and 89.0–108.9% for all analytes. This validated method was applied to the determination of plasma samples in lung cancer patients receiving 150 mg of oral erlotinib. The plasma concentration ranges of erlotinib, OSI‐413 and OSI‐420 were 373–2354, 15.7–379 and 2.5–43.6 ng/mL, respectively. In conclusion, the present method can be helpful for evaluating the plasma exposures of erlotinib and its major isomeric metabolites in clinical settings. Copyright © 2014 John Wiley & Sons, Ltd.     

Rattling in the Quadruple Perovskite CuCu3V4O12

Of particular interest is a peculiar motion of guest atoms or ions confined to nanospace in cage compounds, called rattling. While rattling provides unexplored physical properties through the guest–host interactions, it has only been observed in a very limited class of materials. Herein, we introduce an A‐site‐ordered quadruple perovskite, CuCu₃V₄O₁₂, as a new family of cage compounds. This novel AA′₃B₄O₁₂‐type perovskite has been obtained by a high‐pressure synthesis technique and structurally characterized to have cubic Im$\bar 3$ symmetry with an ionic model of Cu²⁺Cu²⁺₃V⁴⁺₄O₁₂. The thermal displacement parameter of the A‐site Cu²⁺ ion is as large as U_iso≈0.045 Ų at 300 K, indicating its large‐amplitude thermal oscillations in the oversized icosahedral cages. Remarkably, the presence of localized phonon modes associated with rattling of the A‐site Cu²⁺ ion manifests itself in the low‐temperature specific heat data. This work sheds new light on the structure–property relations in perovskites.     

Calibration transfer employing univariate correction and robust regression

This paper proposes a new method for calibration transfer, which was specifically designed to work with isolated variables, rather than the full spectrum or spectral windows. For this purpose, a univariate procedure is initially employed to correct the spectral measurements of the secondary instrument, given a set of transfer samples. A robust regression technique is then used to obtain a model with low sensitivity with respect to the univariate correction residuals. The proposed method is employed in two case studies involving near infrared spectrometric determination of specific mass, research octane number and naphthenes in gasoline, and moisture and oil in corn. In both cases, better calibration transfer results were obtained in comparison with piecewise direct standardization (PDS). The proposed method should be of a particular value for use with application-targeted instruments that monitor only a small set of spectral variables.     

An N-protection free ligation of the peptide thioester and the peptide with an N-alkoxy- or N-aryloxyamino group at its N-terminus

Peptides with an N-alkoxy or N-aryloxy amino acid at their N-terminus were synthesized and successfully ligated with a peptide thioester by silver ion activation under a slightly acidic condition without requiring protection of the side chain amino groups. The N-methoxy group was easily cleaved by the SmI₂ reduction in CH₃OH aq. to obtain the desired peptide with a native peptide bond. This method was successfully applied to the synthesis of the human atrial natriuretic peptide showing the efficiency of the novel ligation.     

Transportation of a microdroplet on an oriented liquid crystal surface

Wetting phenomena play important roles in several technological applications and in many physical and biological thin‐film phenomena, such as wetting, adhesion and friction. One of key issues of these studies is to control the surface energy (or wettability) dynamically for liquid transportation. We have developed a liquid crystal (LC) surface for use as a transport substrate since we expected that the surface energy of an LC surface can be controlled rapidly using an electric field. The rapid control of the polarisability (or wettability) of a liquid crystalline surface by an electric field has been demonstrated, together with the transportation of a liquid microdroplet.     

Simple and validated UHPLC method coupled to UV detection for determination of daptomycin in human plasma and urine

Daptomycin, a lipopeptide antibiotic with excellent activity against Gram‐positive bacteria, is excreted primarily by the kidneys. Development of effective chromatographic methodologies for the determination of daptomycin in human specimens is necessary for clinical use. This study developed a simple and validated ultra‐high‐performance liquid chromatography method coupled to ultraviolet detection for determination of daptomycin in human plasma and urine. After the pretreatments involving protein precipitation, the supernatants were separated using a 2.3 µm particle size octadecylsilyl column, and the run time was 1 min. The calibration curves were linear over the concentration ranges of 2–200 mg/L for plasma and 25–300 mg/L for urine. Intra‐ and inter‐assay precision and accuracy values of plasma were within 13.5 and 92–100% and within 10.7 and 100–107%, respectively. Those of urine were within 5.0 and 101–104% and within 3.7 and 100–101%, respectively. The validated method was applied to the determination of plasma and urine samples in patients receiving 4–6 mg/kg of intravenous daptomycin, resulting in sufficient sensitivity for evaluating the plasma exposure and urinary excretion. In conclusion, the present method with acceptable analytical performance can be helpful for evaluating the pharmacokinetic disposition of daptomycin in clinical settings. Copyright © 2013 John Wiley & Sons, Ltd.