A beta-lactone route to chiral gamma-substituted alpha-amino acids: application to the concise synthesis of (S)-alpha-azidobutyro lactone and a natural amino acid

[reaction: see text] Beta-lactones are useful synthetic intermediates allowing access to a number of functional arrays. In this report, enantiomerically pure 4-trichloromethyl-2-oxetanone is shown to be a versatile amino acid synthon leading to a variety of gamma-substituted alpha-amino acid precursors. The utility of this methodology was demonstrated by the concise synthesis of a protected homoserine equivalent, alpha-azidobutyro lactone, and a naturally occurring alpha-amino acid from the seeds of Blighia unijugata.     

Long-term neprilysin gene transfer is associated with reduced levels of intracellular Abeta and behavioral improvement in APP transgenic mice

Background  

Proteolytic degradation has emerged as a key pathway involved in controlling levels of the Alzheimer's disease (AD)-associated amyloid-β (Aβ) peptide in the brain. The endopeptidase, neprilysin, has been implicated as a major Aβ degrading enzyme in mice and humans. Previous short and intermediate term studies have shown the potential therapeutic application of neprilysin by delivering this enzyme into the brain of APP transgenic mice using gene transfer with viral vectors. However the effects of long-term neprilysin gene transfer on other aspects of Aβ associated pathology have not been explored yet in APP transgenic mice.     

Analysis of HRTEM images for carbon nanostructure quantification

Image processing algorithms have been developed to extract fringe length, tortuosity and separation from high resolution transmission electron microscopy images. To validate the separation algorithm, a comparison is made between the image-based fringe separation and that obtained by analysis of X-ray diffraction data for a progressively heat-treated carbon black. Agreement is favorable. To illustrate the utility of the analysis parameters for a range of carbon nanostructures, analysis is applied to a series of pyrolytically prepared carbon soots – qualitatively described as containing amorphous, graphitic or fullerenic nanostructure. For all processing, the intermediate image, in the form of a skeletonized binary image of the original high resolution transmission electron micrograph, is shown and found to accurately reflect the nanostructural organization within the carbon as visually observed. Statistical results for each analysis parameter, extracted from the binary images, are presented in the form of histograms and quantitatively distinguish the different carbon nanostructures.     

Molecular structure of Hf(BH4)4 investigated by quantum mechanical calculations and gas-phase electron diffraction

The structure of the gaseous hafnium tetrakis(tetrahydroborate) molecule, Hf(BH4)4, has been investigated by detailed quantum mechanical calculations and by analysis of its gas electron-diffraction (GED) pattern. The ground-state geometry possesses T symmetry with all of the triply-bridged BH4 groups twisted equally about the Hf...B-H axes. Salient structural parameters (ra distances, r angles) deduced from the GED pattern by the SARACEN method were: r(Hf...B) 231.4(2), r(Hf-Hb) 221.5(7), r(B-Hb) 127.6(5), r(B-Ht) 121(1) pm, Hf...B-Hb 69.4(3), Hb-B-Hb 108.4(4), Hb-B-Ht 110.6(3), B...Hf...B-Hb 166(1) degrees. A notable feature is the large magnitude of the Hf...B and Hf-Hb anharmonicity parameters, attributed to the fluxional hydrogen atom exchange process. The properties are compared with those of related tetrahydroborates..     

Synthesis of novel 6,11-O-bridged bicyclic ketolides via a palladium-catalyzed bis-allylation

A bridging chemistry process was developed to form an ether bridge between 6-O and 11-O of erythromycin A via a tandem or stepwise palladium-catalyzed bis-pi-allylation. By applying this bridging process, new 6,11-O-bridged bicyclic ketolides (BBKs) were synthesized. These BBKs showed good antibacterial activities against the macrolide-susceptible strains as well as mef-resistant strains and served as a good core for further modifications to study the structure-activity relationship (SAR) and to overcome bacterial resistance. [reaction: see text]     

The influence of water content, cooling and warming rate upon survival of embryonic axes of Poncirus trifoliata (L.)

The present study investigated the relative contributions of water content and non-equilibrium cooling and warming rates to the survival of cryopreserved axes of recalcitrant P. trifoliata seeds. Reducing water contents from 1.7 and 0.26 g water per g dry mass is believed to increase cytoplasmic viscosity. Cooling to -196 degree C was done at rates averaging between 0.17 and 1300 degree C per second, and warming at 600 or 1.35 degree C per second. Survival was assessed after 4 weeks in vitro. Rapid warming resulted in higher survival and normal development of axes at all water contents. The effects of cooling rate were dependent on the water content of axes. Cooling rates resulting in >70 percent normal development ranged between 0.17 and about 1300 degree C per second for axes at a water content of 0.26 g water per g dry mass narrowing with increasing hydration to an apparent optimum at about 686 degree C per second in axes at 0.8 g water per g dry mass At 1.7 g water per g dry mass, axes cooled at 0.17 degree C per second yielded nearly 40 percent normal development, whereas faster cooling was deleterious. Results are interpreted in the context of the effect of water content on cytoplasmic viscosity and the rate of intracellular ice formation. At low water contents, the high intracellular viscosity slows ice crystallization making survival independent of cooling rate. At higher water contents, the reduced viscosity requires faster cooling to prevent ice crystal damage. The ability to cool rapidly with increasing hydration is balanced with an increasing limitation to dissipate heat fast enough to prevent severe damage.