Efficient synthesis of an imidazole-substituted delta-amino acid by the integration of chiral technologies

Two methods to produce (2S)-5-amino-2-(1-n-propyl-1H-imidazol-4-ylmethyl)-pentanoic acid were investigated. Diastereoisomeric salt resolution, using the quinidine salt, gave the desired intermediate in 98% ee and 33% yield. Asymmetric hydrogenation of various substrates gave high conversions, with up to 83% ee. Integration of these two approaches via asymmetric hydrogenation of a quinidine salt substrate followed by crystallization provided the desired intermediate in 94% ee and 76% yield.     

Characterisation of the comonomer composition and distribution of copolymers using chemometric techniques

Chemometric techniques have been applied to FTIR and DSC data to correlate polymer composition. Since structural differences in the polymers with only hydrocarbon structure, often cause subtle changes in spectra, the ability of chemometric techniques is required to discern these differences. FTIR spectra and thermal fractionation using DSC were measured for 28 types of polyethylenes (PE) varying in chain branching type, content and distribution. Unsupervised clustering methods such as principal component analysis (PCA) and supervised discriminant analysis were used to classify the PEs according to their structural class. The DSC data was the more successful in both classifying PEs according to their class. This revised version was published online in July 2006 with corrections to the Cover Date.     

Two-photon laser spectroscopy of the muonium 1S–2S transition

The 1² S _1/2(F=1)?2² S _1/2(F=1) energy interval in muonium has been investigated by Doppler-free two-photon laser spectroscopy. The transition was observed by uniquely identifying and counting the muons released after the photoionization of the 2S state by the same laser field. The measured transition frequency of 2455 528016(58)(43) MHz is in good agreement with QED calculations. The experiment can be interpreted as a test of the Lamb shift contributions at the 1% level. The method is also well suited for a precise determination of the mass of the positive muon in a muoniumhydrogen isotope shift measurement.     

The use of charge-coupled devices in the quantitative evaluation of images, on photographic film or membranes, obtained following electrophoretic separation of DNA fragments

Charge-coupled devices can provide an excellent means for the quantification of DNA band images on membranes and photographic film. However, proper consideration must be given to important parameters such as signal-to-noise ratio and resolution, especially in applications which demand the use of large format media. When employed in the direct imaging of chemiluminescent blots, the charge-coupled device can provide equal or better sensitivity than that obtained by indirect methods using film, with the additional advantages of wide dynamic range and freedom from the vagaries of film processing.     

Solid- and solution-phase synthesis of vancomycin and vancomycin analogues with activity against vancomycin-resistant bacteria

Vancomycin, the prototypical member of the glycopeptide family of antibiotics, is a clinically used antibiotic employed against a variety of drug-resistant bacterial strains including methicillin-resistant Staphylococcus aureus (MRSA). The recent emergence of vancomycin resistance, viewed as a growing threat to public health, prompted us to initiate a program aimed at restoring the potency of this important antibiotic through chemical manipulation of the vancomycin structure. Herein, we describe the development of synthetic technology based on the design of a novel selenium safety catch linker, application of this technology to a solid-phase semisynthesis of vancomycin, and the solid- and solution-phase synthesis of vancomycin libraries. Biological evaluation of these compound libraries led to the identification of a number of in vitro highly potent antibacterial agents effective against vancomycin-resistant bacteria. In addition to aiding these investigations, the solid-phase chemistry described herein is expected to enhance the power of combinatorial chemistry and facilitate chemical biology and medicinal chemistry studies.