Richard J. Upton

Novel extracellular mycobactins, the carboxymycobactins from Mycobacterium avium

Abstract A series of novel extracellular siderophores, termed carboxymycobactins, have been isolated from M. avium as iron complexes and their structures determined. They are the first extracellular siderophores to be characterised from pathogenic mycobacteria and are analogous to their intracellular mycobactin counterparts, except that their R 1 alkyl sidechain is shorter and terminates in a carboxylic acid, resulting in much greater hydrophilicity and explaining their occurrence in the aqueous extracellular medium.

Development of GSK's NMR guides – a tool to encourage the use of more sustainable solvents

Residual solvents often appear as nuisance signals in experimental NMR spectra, and many chemists turn to well-known literature sources to quickly identify such peaks. While these publications are very useful, they do not currently include many solvents exemplified in green chemistry-related literature. This work provides a single compiled reference for NMR chemical shifts of 80 solvents in each of 6 deuterated NMR solvents. The overall green chemistry assessments, as reached via the methodology of the GSK Solvent Sustainability Guide, are displayed on these charts.

Use of Calculated Physicochemical Properties to Enhance Quantitative Response When Using Charged Aerosol Detection

Universal quantitative detection without the need for analyte reference standards would offer substantial benefits in many areas of analytical science. The quantitative capability of high-performance liquid chromatography (HPLC) with charged aerosol detection (CAD) was investigated for 50 compounds with a wide range of physical and chemical properties. It is widely believed that CAD is a mass detector. Quantification of the 50 compounds using a generic calibrant and mass calibration achieved an average error of 11.4% relative to 1H NMR. Correction factors are proposed that estimate the relative surface area of particles in the detector, taking into account the effects of the density and charge of analytes. Performing these corrections and quantifying with surface area calibration, rather than mass, shows considerably improved linearity and uniformity of detection, reducing the average error relative to 1H NMR to 7.1%. The accuracy of CAD quantification was most significantly improved for highly dense compounds, with traditional mass calibration showing an average error of 34.7% and the newly proposed surface area calibration showing an average error of 5.8%.

A stereoselective synthesis via a 5-exo-trig cyclisation of trans-2-oxohexahydro-2H-furo[3,2-b]pyrroles (pyrrolidine-trans-lactones)—potent, novel elastase inhibitors

trans-2-Oxohexahydro-2H-furo[3,2-b]pyrroles (such as 2) are conformationally strained 5,5-fused ring systems and are potent human neutrophil elastase (HNE) inhibitors. A stereoselective synthesis is described based on intramolecular 5-exo-trig cyclisations of aldehyde acrylates 4 and 5 mediated by samarium(II) iodide to give predominantly trans-products 9 and 15. The n-propyl group in 15 is also generated with stereoselectivity for the desired β-isomer.