Vinylic MIDA Boronates: New Building Blocks for the Synthesis of Aza‐Heterocycles

A two‐step synthesis of structurally diverse pyrrole‐containing bicyclic systems is reported. ortho‐Nitro‐haloarenes coupled with vinylic N‐methyliminodiacetic acid (MIDA) boronates generate ortho‐vinyl‐nitroarenes, which undergo a “metal‐free” nitrene insertion, resulting in a new pyrrole ring. This novel synthetic approach has a wide substrate tolerance and it is applicable in the preparation of more complex “drug‐like” molecules. Interestingly, an ortho‐nitro‐allylarene derivative furnished a cyclic β‐aminophosphonate motif.     

Enantiomers of polarized alkenes: chromatographic enrichment and thermal interconversion

(+)- and (?)-$\text{1}$ as well as (+)- and (?)-$\text{2}$ were partially separated by liquid chromatography on triacetylcellulose; racemizations resulted in the barriers (Table 2) to rotation via planarized transition states.     

Altered extracellular striatal in vivo biotransformation of the opioid neuropeptide dynorphin A(1-17) in the unilateral 6-OHDA rat model of Parkinson's disease

The in vivo biotransformation of dynorphin A(1-17) (Dyn A) was studied in the striatum of hemiparkinsonian rats by using microdialysis in combination with nanoflow reversed-phase liquid chromatography/electrospray time-of-flight mass spectrometry. The microdialysis probes were implanted into both hemispheres of unilaterally 6-hydroxydopamine (6-OHDA) lesioned rats. Dyn A (10 pmol microl(-1)) was infused through the probes at 0.4 microl min(-1) for 2 h. Samples were collected every 30 min and analyzed by mass spectrometry. The results showed for the first time that there was a difference in the Dyn A biotransformation when comparing the two corresponding sides of the brain. Dyn A metabolites 1-8, 1-16, 5-17, 10-17, 7-10 and 8-10 were detected in the dopamine-depleted striatum but not in the untreated striatum. Dyn A biotransformed fragments found in both hemispheres were N-terminal fragments 1-4, 1-5, 1-6, 1-11, 1-12 and 1-13, C-terminal fragments 2-17, 3-17, 4-17, 7-17 and 8-17 and internal fragments 2-5, 2-10, 2-11, 2-12, and 8-15. The relative levels of these fragments were lower in the dopamine-depleted striatum. The results imply that the extracellular in vivo processing of the dynorphin system is being disturbed in the 6-OHDA-lesion animal model of Parkinson's disease.     

Investigation of the40Ca(γ,N) reaction at 60 MeV

The values of the angle-integrated cross section for the decay to various low-lying states in³⁹K following the⁴⁰Ca(,) reaction at a mean photon energy of 60 MeV are reported on, together with the values of the reduced Legendre coefficientsa _i . The⁴⁰Ca(,gp) and⁴⁰Ca(,n) reactions yield the same angular cross-section values and these agree with the corresponding RPA-calculations.Senior Research Associate NFWO     

On-line SFE-GC for determination of PCBs in human milk and blood serum

On-line coupled supercritical fluid extraction and gas chromatography (SFE-GC) has been utilized for the determination of PCBs and other organochlorine compounds in human milk and blood serum. The procedure involved preconcentration of the sample on C₁₈-silica sorbent in an extraction cell: after precipitation of the proteins up to 20 ml of human milk was concentrated on 0.5 g of sorbent. Serum (up to 5 ml) was applied to the C₁₈ material without pretreatment. Basic alumina was utilized as a selective adsorbent for lipids in the on-line SFE-GC system. The method was used to analyze milk and serum spiked with 0.5 and 10 ng of Aroclor 1260 and the results compared with those obtained by liquid–liquid extraction of serum.     

Differentiation and quantification of synthetic phosphatidylethanol (PEth) homologues by 1H- and 13C-NMR in polar organic solvents

Various phosphatidylethanol (PEth) derivatives, the corresponding reversed positional isomers (RPI-PEths), lyso-PEth-16:0, and penta-deuterium-labeled PEth analogs (d5-PEths), were synthesized by enzyme-independent synthetic routes. A general solvent system consisting of a mixture of acetone-d6 and methanol-d4 (97:3; v/v) was found to provide a good solubilizing capacity and excellent hydrogen-1 NMR (¹H-NMR) peak resolution of various PEth homologues. Analytical differentiation of PEth from the corresponding RPI-PEth by carbon-13 NMR (¹³C-NMR) was demonstrated by comparison of the ¹³C-NMR signals of the carbonyl groups, the allylic positions, and of the β-carbons. An exemplary stable long-term room temperature, DMSO-d6-based, and proton-sensitive quantitative nuclear magnetic resonance (¹H-qNMR) independently quantified calibrator comprising PEth-16:0/18:1 for liquid chromatography (tandem) mass spectrometry (LC-MS/MS) analytical applications were prepared by employment of sodium dodecyl sulfate (SDS) as a solubilizing additive. In summary, novel hypothetically occurring PEth derivatives, e.g., RPI-PEths, have been independently synthesized with regio- and stereochemical control. Use of polar organic solvents, e.g., mixtures of acetone-d6 and methanol-d4 or DMSO-d6, improves spectral line shapes as compared to traditional hydrophobic solvents and allow for analytical differentiation between closely related PEth derivatives, as well as LC-MS/MS-independent concentration determination of dissolved single species by employment of ¹H-qNMR.

Experimental and four‐component relativistic DFT studies of tungsten carbonyl complexes

We present a theoretical and experimental study of the structure and nuclear magnetic resonance (NMR) parameters of the pentacarbonyltungsten complexes of η¹‐2‐(trimethylstannyl)‐4,5‐dimethylphosphinine, η²‐norbornene, and imidazolidine‐2‐thione. The three complexes have a pseudo‐octahedral molecular structure with the six ligands bonded to the tungsten atom. The η¹‐2‐(trimethylstannyl)‐4,5‐dimethylphosphinine‐pentacarbonyl tungsten complex was synthesized for the first time. For all compounds, we present four‐component relativistic calculations of the NMR parameters at the Dirac–Kohn–Sham density functional level of theory using hybrid functionals. These large‐scale relativistic calculations of NMR chemical shifts and spin–spin coupling constants were compared with available experimental data, either taken from the literature or measured in this work. The inclusion of solvent effects modeled using a conductor‐like screening model was found to improve agreement between the calculated and experimental NMR parameters, and our best estimates for the NMR parameters are generally in good agreement with available experimental results. The present work demonstrates that four‐component relativistic theory has reached a level of maturity that makes it a convenient and accurate tool for modeling and understanding chemical shifts and indirect spin–spin coupling constants of organometallic compounds containing heavy elements, for which conventional non‐relativistic theory breaks down. Copyright © 2015 John Wiley & Sons, Ltd.     

Dendrobeaniamine A,a new alkaloid from the Arctic marine bryozoan Dendrobeania murrayana

Abstract

The new guanidine alkaloid Dendrobeaniamine A (1) was isolated from the organic extract of the Arctic marine bryozoan Dendrobeania murrayana. The chemical structure of 1 was elucidated by spectroscopic experiments, including 1D and 2D NMR and HRESIMS analysis. Compound 1 is a lipoamino acid, consisting of a C₁₂ fatty acid anchored to the amino acid arginine. The bioactivity of 1 was evaluated using cellular and biochemical assays, but the compound did not show cytotoxic, antimicrobial, anti-inflammatory or antioxidant activities     

Retention mechanisms and selectivity in internal-surface reversed-phase liquid chromatography. Studies with cyanobacterial peptide toxins

Summary Microcystins-LA,-LR,-RR,-YR and nodularin, cyanobacterial peptide toxins, were separated by internal-surface reversed-phase (ISRP), high-performance liquid chromatography. The capacity factors of the toxins were measured in the range pH 2–8 using acetonitrile, isopropanol or tetrahydrofuran in potassium dihydrogenphosphate mobile phase. The main retention mechanism of the ISRP column was reversed-phase interaction but cation-exchange offered additional selectivity at neutral and slightly acidic pH. At neutral pH (10% modifier, 0.1 M buffer) the elution order was microcystin-LA (two nonpolar residues leucine and alanine as the variable amino acids), nodularin, microcystin-LR,-YR and-RR (two basic arginines as the variable amino acids). The retention times of all toxins except microcystin-RR were substantially longer at acidic pH. At pH 2 (10% modifier, 0.1 M buffer) where the cation-exchange mechanism was inoperative the elution order was changed to microcystin-RR, nodularin, microcystin-LR,-YR and-LA. The best separation was achieved at pH 2 where even two desmethylated microcystin-RR analogs could be separated from microcystin-RR.