Switching the stereochemical outcome of 6-endo-trig cyclizations; Synthesis of 2,6-Cis-6-substituted 4-oxopipecolic acids

A base-mediated 6-endo-trig cyclization of readily accessible enone-derived α-amino acids has been developed for the direct synthesis of novel 2,6-cis-6- substituted-4-oxo-L-pipecolic acids. A range of aliphatic and aryl side chains were tolerated by this mild procedure to give the target compounds in good overall yields. Molecular modeling of the 6-endo-trig cyclization allowed some insight as to how these compounds were formed, with the enolate intermediate generated via an equilibrium process, followed by irreversible tautomerization/neutralization providing the driving force for product formation. Stereoselective reduction and deprotection of the resulting 2,6-cis-6-substituted 4-oxo-L-pipecolic acids to the corresponding 4-hydroxy-L-pipecolic acids was also performed

Modeling the impact of melt on seismic properties during mountain building

Initiation of partial melting in the mid/lower crust causes a decrease in P-wave and S-wave velocities; recent studies imply that the relationship between these velocities and melt is not simple. We have developed a modelling approach to assess the combined impact of various melt and solid phase properties on seismic velocities and anisotropy. The modelling is based on crystallographic preferred orientation (CPO) data measured from migmatite samples, allowing quantification of the variation of seismic velocities with varying melt volumes, shapes, orientations, and matrix anisotropy. The results show non-linear behaviour of seismic properties as a result of the interaction of all of these physical properties, which in turn depend on lithology, stress regime, strain rate, pre-existing rock fabrics, and pressure-temperature conditions. This non-linear behaviour is evident when applied to a suite of samples from a traverse across a migmatitic shear zone in the Seiland Igneous Province, Northern Norway. Critically, changes in solid phase composition and CPO, and melt shape and orientation with respect to the wave propagation direction can result in huge variations in the same seismic property even if the melt fraction remains the same. A comparison with surface wave interpretations from tectonically active regions highlights the issues in current models used to predict melt percentages or partially molten regions. Interpretation of seismic data to infer melt percentages or extent of melting should, therefore, always be underpinned by robust modelling of the underlying geological parameters combined with examination of multiple seismic properties in order to reduce uncertainty of the interpretation

Eocene and Miocene extension, meteoric fluid infiltration, and core complex formation in the Great Basin (Raft River Mountains, Utah)

Metamorphic core complexes (MCCs) in the North American Cordillera reflect the effects of lithospheric extension and contribute to crustal adjustments both during and after a protracted subduction history along the Pacific plate margin. While the Miocene-to-recent history of most MCCs in the Great Basin, including the Raft River-Albion-Grouse Creek MCC, is well documented, early Cenozoic tectonic fabrics are commonly severely overprinted. We present stable isotope, geochronological (40Ar/39Ar), and microstructural data from the Raft River detachment shear zone. Hydrogen isotope ratios of syntectonic white mica (δ2Hms) from mylonitic quartzite within the shear zone are very low (-90‰ to -154‰, Vienna SMOW) and result from multiphase synkinematic interaction with surface-derived fluids. 40Ar/39Ar geochronology reveals Eocene (re)crystallization of white mica with δ2Hms ≥ -154‰ in quartzite mylonite of the western segment of the detachment system. These δ2Hms values are distinctively lower than in localities farther east (δ2Hms ≥ -125‰), where 40Ar/39Ar geochronological data indicate Miocene (18-15 Ma) extensional shearing and mylonitic fabric formation. These data indicate that very low δ2H surface-derived fluids penetrated the brittle-ductile transition as early as the mid-Eocene during a first phase of exhumation along a detachment rooted to the east. In the eastern part of the core complex, prominent top-to-the-east ductile shearing, mid-Miocene 40Ar/39Ar ages, and higher δ2H values of recrystallized white mica, indicate Miocene structural and isotopic overprinting of Eocene fabrics

Quantification of three macrolide antibiotics in pharmaceutical lots by HPLC: Development, validation and application to a simultaneous separation

A new validated high performance liquid chromatographic (HPLC) method with rapid analysis time and high efficiency, for the analysis of erythromycin, azithromycin and spiramycin, under isocratic conditions with ODB RP18 as a stationary phase is described. Using an eluent composed of acetonitrile –2-methyl-2-propanol –hydrogenphosphate buffer, pH 6.5, with 1.5% triethylamine (33:7: up to 100, v/v/v), delivered at a flow-rate of 1.0 mL min-1. Ultra Violet (UV) detection is performed at 210 nm. The selectivity is satisfactory enough and no problematic interfering peaks are observed. The procedure is quantitatively characterized and repeatability, linearity, detection and quantification limits are very satisfactory. The method is applied successfully for the assay of the studied drugs in pharmaceutical dosage forms as tablets and powder for oral suspension. Recovery experiments revealed recovery of 97.13–100.28%

Accuracy of Herdsmen Reporting versus Serologic Testing for Estimating Foot-and-Mouth Disease Prevalence

Herdsman-reported disease prevalence is widely used in veterinary epidemiologic studies, especially for diseases with visible external lesions; however, the accuracy of such reports is rarely validated. Thus, we used latent class analysis in a Bayesian framework to compare sensitivity and specificity of herdsman reporting with virus neutralization testing and use of 3 nonstructural protein ELISAs for estimates of foot-and-mouth disease (FMD) prevalence on the Adamawa plateau of Cameroon in 2000. Herdsman-reported estimates in this FMD-endemic area were comparable to those obtained from serologic testing. To harness to this cost-effective resource of monitoring emerging infectious diseases, we suggest that estimates of the sensitivity and specificity of herdsmen reporting should be done in parallel with serologic surveys of other animal diseases.Fil: Morgan, Kenton L.. University of Liverpool; Reino UnidoFil: Handel, Ian G.. University of Edinburgh; Reino UnidoFil: Tanya, Vincent N.. Institute of Agricultural Research for Development; Camerún. Ministry of Scientific Research and Innovation; CamerúnFil: Hamman, Saidou M.. Institute of Agricultural Research for Development; CamerúnFil: Nfon, Charles. Institute of Agricultural Research for Development; CamerúnFil: Bergmann, Ingrid Evelyn. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencias y Tecnología "Dr. Cesar Milstein"; Argentina. Pan American Foot and Mouth Disease Center; BrasilFil: Malirat, Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencias y Tecnología "Dr. Cesar Milstein"; Argentina. Pan American Foot and Mouth Disease Center; BrasilFil: Sorensen, Karl J.. Danish Veterinary Institute for Virus Research; DinamarcaFil: Bronsvoort, Barend M de C,. University of Edinburgh; Reino Unid

Synthesis and antiviral activity of water-soluble esters of acyclovir [9-[(2-hydroxyethoxy)methyl]guanine]

Several water-soluble ester derivatives of acyclovir [9-[(2-hydroxyethoxy)methyl]guanine], i.e., the 2'-O-glycyl-, 2'-O-alpha-alanyl-, 2'-O-beta-alanyl- and 2'-O-3-carboxypropionyl esters, were synthesized and evaluated for their antiviral activity in cell culture. The compounds were all prepared directly from acyclovir by application of the usual esterification methods with the appropriate acyl precursors and isolated as their hydrochloride or sodium salts. When assayed in primary rabbit kidney cell cultures against various herpes simplex virus type 1 and type 2 strains, the four acyclovir esters proved almost as active as acyclovir itself, suggesting that they were readily hydrolyzed to release the parent compound.status: publishe