Solid-phase synthesis of dihydrovirginiamycin S1, a streptogramin B antibiotic

We describe the first solid-phase synthesis of dihydrovirginiamycin S(1), a member of the streptogramin B family of antibiotics, which are nonribosomal-peptide natural products produced by Streptomyces. These compounds, along with the synergistic group A components, are "last line of defense" antimicrobial agents for the treatment of life-threatening infections such as vancomycin-resistant enterococci. The synthesis features an on-resin cyclization and is designed to allow production of streptogramin B analogues with diversification at positions 1', 1, 2, 3, 4, and 6. Several synthetic challenges known to hinder the synthesis of this class of compounds were solved, including sensitivity to acids and bases, and epimerization and rearrangements, through the judicious choice of deprotection conditions, coupling conditions, and synthetic strategy. This work should enable a better understanding of structure-activity relationships in the streptogramin B compounds, possible identification of analogues that bypass known resistance mechanisms, and perhaps the identification of analogues with novel biological activities.     

A convenient synthetic route to new bis(arenediazo) complexes of molybdenum and tungsten

Complexes of the type [(C₅H₅)Mo(N₂Ar)(N₂Ar′)(PPh₃)] [PF₆] have been prepared and shown to be useful starting materials for the synthesis of a variety of neutral, cationic or anionic compounds containing [cis-Mo(N₂Ar)(N₂Ar′)]²⁺ units.     

Generation and characterization of phenylsulfanylcarbene

A photosensitive precursor (1) to phenylsulfanylcarbene 2 has been synthesized. Laser flash photolysis (308 nm) of 1 and chemical trapping studies of 2 are reported. [structure: see text]     

Age determination of a 75Se gamma radiography source for nuclear forensics

Journal of Radioanalytical and Nuclear Chemistry - Two methods were used to evaluate the age of 75Se sealed source material. Both methods utilized gamma spectroscopy to determine the quantity of...     

Peptide conjugated cellulose nanocrystals with sensitive human neutrophil elastase sensor activity

In chronic wounds, elevated human neutrophil elastase (HNE) is a destructive protease that has been proposed as a biomarker. Numerous wound dressing designs have been introduced in an effort to lower HNE levels. The clinical detection of HNE as a point of care biomarker or an in situ colorimetric adjuvant to chronic wound dressings presents potential advantages in the management of chronic wounds. A colorimetric approach to the detection of HNE using peptide conjugated cotton cellulose nanocrystals (CCN) is reported here. For this purpose a HNE tripeptide substrate, n-Succinyl-Alanine–Alanine-Valine-para-nitroanilide (Suc-Ala–Ala-Val-pNA), was covalently attached to glycine esterified CCN and compared with a similar tetrapeptide analog for colorimetric HNE sensor activity. Visible HNE activity was significantly higher on CCN tripeptide conjugates when compared with similar analogs synthesized on paper. Upon enzymatic release of para-nitroaniline (pNA) from the Glycine-CCN conjugate of succinyl-Ala–Ala-Val-pNA, amplification of the colorimetric response from pNA with reactive dyes enhanced visible absorption of the chromogen. Two color amplifying dyes that react with pNA were compared for their ability to enhance the visual sensor response to HNE activity. The colorimetric detection of HNE with CCN tripeptide conjugates was sensitive at HNE levels previously reported in chronic wound fluid (0.05 U/mL HNE). The HNE sensor and the chromogen amplifying dyes were interfaced with 50 and 10 kD dialysis cellulose membranes (DCM) to model filtration of HNE and chromogen (pNA) from a model wound dressing surface before and after sensor reactivity. The detection sensitivity to HNE activity was assessed with the CCN-tripeptide conjugate interfaced at the DCM surface distal and proximal to a dressing surface. The HNE sensor interfaced proximal to the dressing surface was most efficient with 10 kD membrane filtration of pNA and subsequent reaction with amplifying dyes. When interfaced with the 10 kD cellulose membrane, elastase sensor activity remained sensitive to 0.05 U/mL HNE. The nanocellulose surface properties, performance and design issues of the biosensor approach are discussed.     

QUADRATURE METHODS FOR HIGHLY OSCILLATORY SINGULAR INTEGRALS

We address the evaluation of highly oscillatory integrals,with power-law and logarithmic singularities.Such problems arise in numerical methods in engineering.Notably,the evaluation of oscillatory integrals dominates the run-time for wave-enriched boundary integral formulations for wave scattering,and many of these exhibit singularities.We show that the asymptotic behaviour of the integral depends on the integrand and its derivatives at the singular point of the integrand,the stationary points and the endpoints of the integral.A truncated asymptotic expansion achieves an error that decays faster for increasing frequency.Based on the asymptotic analysis,a Filon-type method is constructed to approximate the integral.Unlike an asymptotic expansion,the Filon method achieves high accuracy for both small and large frequency.Complex-valued quadrature involves interpolation at the zeros of polynomials orthogonal to a complex weight function.Numerical results indicate that the complex-valued Gaussian quadrature achieves the highest accuracy when the three methods are compared.However,while it achieves higher accuracy for the same number of function evaluations,it requires signi cant additional cost of computation of orthogonal polynomials and their zeros.     

Analysis of pp → K+K− π+π− around 1 GeV/c

Approximately 100 000 four-prong antiproton annihilations in hydrogen were measured. A clean, unbiased sample of 842 K⁺K^?π⁺π^? events was obtained. This reaction is dominated by $\text{K}{}^1\text{(～45\%)}$ and ?⁰(～20%) production, with smaller amounts of A₂⁰(～15%) and ?(～5%) production. 25% of the reactions involved double resonance production. No significant three-body resonance production is observed.