Catalytic asymmetric synthesis of a 1-deoxy-1,1-difluoro-D-xylulose

[reaction: see text] A new route, of potential strategic importance, to a difluorosugar analogue has been developed. Key steps included a Stille coupling and a highly regio- and enantioselective dihydroxylation of a highly substituted diene. Protecting groups were chosen to enhance the reactivity of the disubstituted allylic fragment in the AD reaction and allow deprotection under orthogonal conditions.     

Asymmetric Synthesis of Heterocyclic Chloroamines and Aziridines by Enantioselective Protonation of Catalytically Generated Enamines**

We report a method for the synthesis of chiral vicinal chloroamines via asymmetric protonation of catalytically generated prochiral chloroenamines using chiral Brønsted acids. The process is highly enantioselective, with the origin of asymmetry and catalyst substituent effects elucidated by DFT calculations. We show the utility of the method as an approach to the synthesis of a broad range of heterocycle-substituted aziridines by treatment of the chloroamines with base in a one-pot process, as well as the utility of the process to allow access to vicinal diamines.     

Synthesis of functional "top-half" partial structures of azinomycin a and B

The design and synthesis of a detailed series of functional "top-half" substructures of azinomycin A and B is described.     

Stimulated Raman scattering microscopy with spectral phasor analysis: applications in assessing drug–cell interactions

Statins have displayed significant, although heterogeneous, anti-tumour activity in breast cancer disease progression and recurrence. They offer promise as a class of drugs, normally used for cardiovascular disease control, that could have a significant impact on the treatment of cancer. Understanding their mode of action and accurately assessing their efficacy on live cancer cells is an important and significant challenge. Stimulated Raman scattering (SRS) microscopy is a powerful, label-free imaging technique that can rapidly characterise the biochemical responses of live cell populations following drug treatment. Here, we demonstrate multi-wavelength SRS imaging together with spectral phasor analysis to characterise a panel of breast cancer cell lines (MCF-7, SK-BR-3 and MDA-MB-231 cells) treated with two clinically relevant statins, atorvastatin and rosuvastatin. Label-free SRS imaging within the high wavenumber region of the Raman spectrum (2800–3050 cm⁻¹) revealed the lipid droplet distribution throughout populations of live breast cancer cells using biocompatible imaging conditions. A spectral phasor analysis of the hyperspectral dataset enables rapid differentiation of discrete cellular compartments based on their intrinsic SRS characteristics. Applying the spectral phasor method to studying statin treated cells identified a lipid accumulating phenotype in cell populations which displayed the lowest sensitivity to statin treatment, whilst a weaker lipid accumulating phenotype was associated with a potent reduction in cell viability. This study provides an insight into potential resistance mechanisms of specific cancer cells towards treatment with statins. Label-free SRS imaging provides a novel and innovative technique for phenotypic assessment of drug-induced effects across different cellular populations and enables effective analysis of drug–cell interactions at the subcellular scale.

Stimulated Raman scattering microscopy with spectral phasor analysis provides a label-free approach for phenotypic evaluation of drug-induced effects.     

Reaction of 1,1′‐Divinyl Ferrocene with One‐Electron Oxidants: Entry into Functionalised [4]Ferrocenophanes and Observation of an Isotope‐Dependent Chemoselectivity Effect

1,1′‐Divinyl ferrocene ( 2 ) reacts with K₃[Fe(CN)₆] under basic biphasic conditions to give a [4]ferrocenophane ( 4 ) in good yield. Incorporating deuterium labels into the internal positions of the vinyl groups of 2 affects the chemoselectivity of the reaction; thus under identical reaction conditions, [D₂]‐ 2 reacts to provide a diol‐functionalised [4]ferrocenophane, [D₂]‐D /L ‐ 6 in addition to the expected keto‐alcohol, [D₁]‐ 4 . Variants on this one‐electron oxidative cyclisation methodology can be used to give other [4]ferrocenophanes; thus, the reaction of 2 with CuCl₂ in MeOH or iPrOH leads to dialkoxy [4]ferrocenophanes 19 and 20 , respectively, whereas the reaction of 2 with benzyl carbamate in the presence of tBuOCl gives a bis(carbamate)[4]ferrocenophane, 21 . Mechanisms to account for the formation of the products, the stereoselectivity, and the unusual isotope‐dependent chemoselectivity in the reaction of 2 and [D₂]‐ 2 with K₃[Fe(CN)₆] are proposed.     

Screening and quantitative confirmatory method for the analysis of glucocorticoids in bovine milk using liquid chromatography-tandem mass spectrometry

An LC/MS/MS method was developed and validated for the simultaneous identification, confirmation, and quantification of 12 glucocorticoids in bovine milk. The method was validated in accordance with the criteria defined in Commission Decision 2002/657/EC. The developed method can detect and confirm the presence of dexamethasone, betamethasone, prednisolone, flumethasone, 6alpha-methylprednisolone, fluorometholone, triamcinolone acetonide, prednisone, cortisone, hydrocortisone, clobetasol propionate, and clobetasol butyrate in bovine milk. Milk samples are extracted with acetonitrile; sodium chloride is subsequently added to aid partition of the milk and acetonitrile mixture. The acetonitrile extract is then subjected to liquid-liquid purification by the addition of hexane. The purified extract is evaporated to dryness and reconstituted in a water-acetonitrile mixture, and determination is carried out by LC/MS/MS. The method permits analysis of up to 30 samples in 1 day.