A Rapid Synthesis of 4‐Oxazolidinones: Total Synthesis of Synoxazolidinones A and B

A five‐step total synthesis of the marine natural product synoxazolidinone A was achieved through a diastereoselective imine acylation/cyclization cascade. Synoxazolidinone B and a series of analogues were also prepared to explore the potential of these 4‐oxazolidinone natural products as antimicrobial agents. These studies confirmed the importance of the chlorine substituent for antimicrobial activity and revealed simplified dichloro derivatives that are equally potent against several bacterial strains.     

Aqueous Ln(III) luminescence agents derived from a tasty precursor

The synthesis, characterization, and photophysical properties are reported for several Ln(III) complexes of a tetradentate chelate, 5LIO-MAM, derived from the common flavor enhancer "maltol". Eu(III), Yb(III), and Nd(III) form stable ML2 complexes in aqueous solution that emit in the red or near-infrared (NIR) upon excitation at ca. 330 nm. The synthesis, aqueous stability, and photophysical properties are reported for a novel tetradentate ligand derived from maltol, a commonly used flavor enhancer. In aqueous solution, this chelate forms stable complexes with Ln(III) cations, and sensitized emission was observed from Eu(III), Yb(III), and Nd(III). A comparison with recently reported and structurally analogous ligands reveals a slightly higher basicity but lower complex stability with Eu(III) [pEu = 14.7(1)]. A very poor metal-centered quantum yield with Eu(III) was observed (Phi(tot) = 0.04%), which can be rationalized by the similar energy of the ligand triplet state and the Eu(III) (5)D0 emissive level. Instead, sensitized emission from the Yb(III) and Nd(III) cations was observed, which emit in the NIR.     

Epitaxial oxide bilayer on Pt (001) nanofacets

We observed an epitaxial, air-stable, partially registered (2 × 1) oxide bilayer on Pt (001) nanofacets [V. Komanicky, A. Menzel, K.-C. Chang, and H. You, J. Phys. Chem. 109, 23543 (2005)]. The bilayer is made of two half Pt layers; the top layer has four oxygen bonds and the second layer two. The positions and oxidation states of the Pt atoms are determined by analyzing crystal truncation rods and resonance scattering data. The positions of oxygen atoms are determined by density functional theory (DFT) calculations. Partial registry on the nanofacets and the absence of such registry on the extended Pt (001) surface prepared similarly are explained in DFT calculations by strain relief that can be accommodated only by nanoscale facets.     

Monte Carlo simulations of the dissolution of borosilicate glasses in near-equilibrium conditions

Monte Carlo simulations were performed to investigate the mechanisms of glass dissolution as equilibrium conditions are approached in both static and flow-through conditions. The glasses studied are borosilicate glasses in the compositional range (80 ? x)% SiO₂ (10 + x / 2)% B₂O₃ (10 + x / 2)% Na₂O, where 5 < x < 30%. In static conditions, dissolution/condensation reactions lead to the formation, for all compositions studied, of a blocking layer composed of polymerized Si sites with principally 4 connections to nearest Si sites. This layer forms atop the altered glass layer and shows similar composition and density for all glass compositions considered. In flow-through conditions, three main dissolution regimes are observed: at high flow rates, the dissolving glass exhibits a thin alteration layer and congruent dissolution; at low flow rates, a blocking layer is formed as in static conditions but the simulations show that water can occasionally break through the blocking layer causing the corrosion process to resume; and, at intermediate flow rates, the glasses dissolve incongruently with an increasingly deepening altered layer. The simulation results suggest that, in geological disposal environments, small perturbations or slow flows could be enough to prevent the formation of a permanent blocking layer. Finally, a comparison between predictions of the linear rate law and the Monte Carlo simulation results indicates that, in flow-through conditions, the linear rate law is applicable at high flow rates and deviations from the linear rate law occur under low flow rates (e.g., at near-saturated conditions with respect to amorphous silica). This effect is associated with the complex dynamics of Si dissolution/condensation processes at the glass–water interface.     

Total synthesis of [Ψ[C(═S)NH]Tpg4]vancomycin aglycon, [Ψ[C(═NH)NH]Tpg4]vancomycin aglycon, and related key compounds: reengineering vancomycin for dual D-Ala-D-Ala and D-Ala-D-Lac binding

The total synthesis of [Ψ[C(═S)NH]Tpg(4)]vancomycin aglycon (8) and its unique AgOAc-promoted single-step conversion to [Ψ[C(═NH)NH]Tpg(4)]vancomycin aglycon (7), conducted on a fully deprotected substrate, are disclosed. The synthetic approach not only permits access to 7, but it also allows late-stage access to related residue 4 derivatives, alternative access to [Ψ[CH(2)NH]Tpg(4)]vancomycin aglycon (6) from a common late-stage intermediate, and provides authentic residue 4 thioamide and amidine derivatives of the vancomycin aglycon that will facilitate ongoing efforts on their semisynthetic preparation. In addition to early stage residue 4 thioamide introduction, allowing differentiation of one of seven amide bonds central to the vancomycin core structure, the approach relied on two aromatic nucleophilic substitution reactions for formation of the 16-membered diaryl ethers in the CD/DE ring systems, an effective macrolactamization for closure of the 12-membered biaryl AB ring system, and the defined order of CD, AB, and DE ring closures. This order of ring closures follows their increasing ease of thermal atropisomer equilibration, permitting the recycling of any newly generated unnatural atropisomer under progressively milder thermal conditions where the atropoisomer stereochemistry already set is not impacted. Full details of the evaluation of 7 and 8 along with several related key synthetic compounds containing the core residue 4 amidine and thioamide modifications are reported. The binding affinity of compounds containing the residue 4 amidine with the model D-Ala-D-Ala ligand 2 was found to be only 2-3 times less than the vancomycin aglycon (5), and this binding affinity is maintained with the model d-Ala-d-Lac ligand 4, representing a nearly 600-fold increase in affinity relative to the vancomycin aglycon. Importantly, the amidines display effective dual, balanced binding affinity for both ligands (K(a)2/4 = 0.9-1.05), and they exhibit potent antimicrobial activity against VanA resistant bacteria ( E. faecalis , VanA VRE) at a level accurately reflecting these binding characteristics (MIC = 0.3-0.6 μg/mL), charting a rational approach forward in the development of antibiotics for the treatment of vancomycin-resistant bacterial infections. In sharp contrast, 8 and related residue 4 thioamides failed to bind either 2 or 4 to any appreciable extent, do not exhibit antimicrobial activity, and serve to further underscore the remarkable behavior of the residue 4 amidines.     

Classification of high-speed gas chromatography-mass spectrometry data by principal component analysis coupled with piecewise alignment and feature selection

A useful methodology is introduced for the analysis of data obtained via gas chromatography with mass spectrometry (GC-MS) utilizing a complete mass spectrum at each retention time interval in which a mass spectrum was collected. Principal component analysis (PCA) with preprocessing by both piecewise retention time alignment and analysis of variance (ANOVA) feature selection is applied to all mass channels collected. The methodology involves concatenating all concurrently measured individual m/z chromatograms from m/z 20 to 120 for each GC-MS separation into a row vector. All of the sample row vectors are incorporated into a matrix where each row is a sample vector. This matrix is piecewise aligned and reduced by ANOVA feature selection. Application of the preprocessing steps (retention time alignment and feature selection) to all mass channels collected during the chromatographic separation allows considerably more selective chemical information to be incorporated in the PCA classification, and is the primary novelty of the report. This methodology is objective and requires no knowledge of the specific analytes of interest, as in selective ion monitoring (SIM), and does not restrict the mass spectral data used, as in both SIM and total ion current (TIC) methods. Significantly, the methodology allows for the classification of data with low resolution in the chromatographic dimension because of the added selectivity from the complete mass spectral dimension. This allows for the successful classification of data over significantly decreased chromatographic separation times, since high-speed separations can be employed. The methodology is demonstrated through the analysis of a set of four differing gasoline samples that serve as model complex samples. For comparison, the gasoline samples are analyzed by GC-MS over both 10-min and 10-s separation times. The successfully classified 10-min GC-MS TIC data served as the benchmark analysis to compare to the 10-s data. When only alignment and feature selection was applied to the 10-s gasoline separations using GC-MS TIC data, PCA failed. PCA was successful for 10-s gasoline separations when the methodology was applied with all the m/z information. With ANOVA feature selection, chromatographic regions with Fisher ratios greater than 1500 were retained in a new matrix and subjected to PCA yielding successful classification for the 10-s separations.