A [2 + 2] cycloaddition route to dimethylaminomethylene vinamidinium salts

[reaction: see text] Trifluoropropanoic acid reacts with 1 equiv of POCl3 in DMF to generate the trifluoromethyl enamine (7). At this stage, two reaction manifolds are available. The expected reaction with additional POCl3 generates the 2-trifluoromethyl vinamidinium salt (3c). However, thermally driven loss of fluoride generates an iminium ion, which sets the stage for a [2 + 2] cycloaddition to ultimately generate the dimethylaminomethylene vinamidinium salt (1).     

Stereoselective 1,2-cis glycosylation of 2-O-allyl protected thioglycosides

The technique of intramolecular aglycon delivery (IAD), whereby a glycosyl acceptor is temporarily appended to a hydroxyl group of a glycosyl donor is an attractive method that can allow the synthesis of 1,2-cis glycosides in an entirely stereoselective fashion. 2-O-Allyl protected thioglycoside donors are excellent substrates for IAD, and may be glycosylated stereoselectively through a three-step reaction sequence. This sequence consists of quantitative yielding allyl bond isomerisation, to produce vinyl ethers that can then undergo N-iodosuccinimide mediated tethering of the desired glycosyl acceptor, and subsequent intramolecular glycosylation, to yield either alpha-glucosides or beta-mannosides accordingly. Although attempted one-pot tethering and glycosylation is hampered by competitive intermolecular reaction with excess glycosyl acceptor, this problem can be simply overcome by the use of excess glycosyl donor. Allyl mediated IAD is a widely applicable practical alternative to other IAD approaches for the synthesis of beta-mannosides, that is equally applicable for alpha-gluco linkages. It is advantageous in terms of both simplicity of application and yield, and in addition has no requirement for cyclic 4,6-protection of the glycosyl donor.     

Gas-Phase Intramolecular Protein Crosslinking via Ion/Ion Reactions: Ubiquitin and a Homobifunctional sulfo-NHS Ester

Gas-phase intra-molecular crosslinking of protein ubiquitin cations has been demonstrated via ion/ion reactions with anions of a homobifunctional N-hydroxysulfosuccinimide (sulfo-NHS) ester reagent. The ion/ion reaction between multiply-protonated ubiquitin and crosslinker monoanions produces a stable, charge-reduced complex. Covalent crosslinking is indicated by the consecutive loss of 2 molecules of sulfo-NHS under ion trap collisional activation conditions. Covalent modification is verified by the presence of covalently crosslinked sequence ions produced by ion-trap collision-induced dissociation of the ion generated from the losses of sulfo-NHS. Analysis of the crosslinked sequence fragments allows for the localization of crosslinked primary amines, enabling proximity mapping of the gas-phase 3-D structures. The presence of two unprotonated reactive sites within the distance constraint of the crosslinker is required for successful crosslinking. The ability to covalently crosslink is, therefore, sensitive to protein charge state. As the charge state increases, fewer reactive sites are available and protein structure is more likely to become extended because of intramolecular electrostatic repulsion. At high charge states, the reagent shows little evidence for covalent crosslinking but does show evidence for ‘electrostatic crosslinking’ in that the binding of the sulfonate groups to the protein is sufficiently strong that backbone cleavages are favored over reagent detachment under ion trap collisional activation conditions.      

A Complex Pyrrolo-oxazinone and Its Iodo Derivative Isolated from a Tunicate

Two cytotoxic triphenylpyrrolo-oxazinones were isolated from a tunicate and their structures elucidated by spectral methods. Lukianol A ( = 3,7,8-tris(4-hydroxyphenyl)pyrrolo[2,1-c][1,4]oxazin-1 (1H)-one; 1 ) had MIC of 1 μg/ml in KB cytotoxicity tests; MIC value for 2 was 100 μg/ml.     

A novel algorithm for chromatogram matching in qualitative analysis

The matching of the pattern of peaks produced during gas chromatography is of importance to many applications. At present, this task is generally performed manually, but this generates the usual problems associated with human inspection, such as a lack of objectivity and reproducibility, proneness to errors, and practical restriction of the volume of data which can reasonably be processed. This paper explores the use of a novel algorithm for automation of this task. The performance of the method on well controlled simulated data sets and real chromatograms is used to show not only how problems of manual inspection can be circumvented, but also how the existence of such a powerful method should open up the possibility of many new analyses for quality control, discrimination of varieties of sample, and the identification of specific components within a sample.     

Protonation and bromination of an osmabenzyne: reactions leading to the formation of new metallabenzynes

The reactivities of benzynes and metal-carbyne complexes are normally associated with the triple bond units. However, we have now found that electrophiles do not attack the formal osmium-carbon triple bond of osmabenzyne complex 1. Instead, 1 undergoes electrophilic substitution reactions-the typical reactions of aromatic systems.     

The involvement of metal-to-CO charge transfer and ligand-field excited states in the spectroscopy and photochemistry of mixed-ligand metal carbonyls. A theoretical and spectroscopic study of [W(CO)(4)(1,2-ethylenediamine)] and [W(CO)(4)(N,N'-bis-alkyl-1,4-diazabutadiene)

A new interpretation of the electronic spectroscopy, photochemistry, and photophysics of group 6 metal cis-tetracarbonyls [M(CO)(4)L(2)] is proposed, that is based on an interplay between M --> L and M --> CO MLCT excited states. TD-DFT and resonance Raman spectroscopy show that the lowest allowed electronic transition of [W(CO)(4)(en)] (en = 1,2-ethylenediamine) has a W(CO(eq))(2) --> CO(ax) charge-transfer character, whereby the electron density is transferred from the equatorial W(CO(eq))(2) moiety to pi orbitals of the axial CO ligands, with a net decrease of electron density on the W atom. The lowest, emissive excited state of [W(CO)(4)(en)] was identified as a spin-triplet W(CO(eq))(2) --> CO(ax) CT excited state both computationally and by picosecond time-resolved IR spectroscopy. This state undergoes 1.5 ps vibrational relaxation/solvation and decays to the ground state with a approximately 160 ps lifetime. The nu(CO) wavenumbers and IR intensity pattern calculated by DFT for the triplet W(CO(eq))(2) --> CO(ax) CT excited state match well the experimental time-resolved spectrum. For [W(CO)(4)(R-DAB)] (R-DAB = N,N'-bis-alkyl-1,4-diazabutadiene), the W(CO(eq))(2) --> CO(ax) CT transition follows in energy the W --> DAB MLCT transition, and the emissive W(CO(eq))(2) --> CO(ax) CT triplet state occurs just above the manifold of triplet W --> DAB MLCT states. No LF electronic transitions were calculated to occur in a relevant energetic range for either complex. Molecular orbitals of both complexes are highly delocalized. The 5d(W) character is distributed over many molecular orbitals, while neither of them contains a predominant metal-ligand sigma 5d(W) component, contrary to predictions of the traditional ligand-field approach. The important spectroscopic, photochemical, and photophysical roles of M(CO(eq))(2) --> CO(ax) CT excited states and the limited validity of ligand field arguments can be generalized to other mixed-ligand carbonyl complexes.     

Targeted lipidomics using electron capture atmospheric pressure chemical ionization mass spectrometry

There is an increasing need to be able to conduct quantitative lipidomics analyses as a complement to proteomics studies. The highest specificity for proteomics analysis can be obtained using methodology based on electrospray ionization (ESI) or atmospheric pressure chemical ionization (APCI) coupled with liquid chromatography/tandem mass spectrometry (LC/MS/MS). For lipidomics analysis it is often necessary to be able to separate enantiomers and regioisomers. This can be very challenging when using methodology based on conventional reversed-phase chromatography. Normal-phase chromatography using chiral columns can provide dramatic improvements in the resolution of enantiomers and regioisomers. However, conventional ESI- and APCI-MS/MS has limited sensitivity, which makes it difficult to conduct studies in cell culture systems where only trace amounts of non-esterified bioactive lipids are present. The use of electron capture APCI-MS/MS overcomes this problem. Enantiomers and regioisomers of diverse bioactive lipids can be quantified using stable isotope dilution methodology coupled with normal-phase chiral chromatography and electron capture APCI-MS/MS. This methodology has allowed a lipidomics profile from rat epithelial cells maintained in culture to be delineated and allowed the effect of a non-selective lipoxygenase inhibitor to be assessed.