Rearrangements of some furan and banzofuran 1.5,-dienols

Isomers of 1-(2-furyl)-methyl-3-buten-ols and their benzofuran analogs were studied for their oxy-Cope and anionic oxy-Cope reactivity.     

The preparation of phenacylpyrazoles,acylpyrazoles, imidazolylisoxazoles and imidazolylpyrazoles from c(α)-dianions of oximes,phenylhydrazones and acylhydrazones

C(α),O-Dilithiooximes, C(α), N-dilithiophenylhydrazones, or C(α), N-dilithioacylhydrazones were prepared in an excess of lithium diisopropylamide (LDA) and condensed with a variety of esters followed by acid-cyclization to give substituted isoxazoles and pyrazoles.     

Discussion of the catalytic pathway of cysteine proteases based on AM1 calculations

The deacylation reaction of the cysteine protease papain was examined by AM1 reaction-coordinate calculations. The transition-state (TS) structure was extracted from the reaction pathway as corresponding to the maximum point along this minimum-energy pathway. Consistent with experimental kinetic data revealing that deacylation is about 60 times faster for thioester (---C(O)---S---) than dithioester (---C(S)---S---) intermediates, calculated E_a values are about 10 kcal mol⁻¹ lower for the former than the latter. The calculated partial atomic charges indicate that the C=O carbon in the thioester is a good site for nucleophilic attack whereas the corresponding C=S carbon in the dithioester is a poor site. The present calculations reveal that the enzyme's oxyanion hole contributes about 9 kcal mol⁻¹ toward reducing E_a for the anionic tetrahedral intermediate and TS structure. On the other hand, the presence of Asn in the putative Asn-His-Cys catalytic triad contributes only about l kcal mol⁻¹ toward reducing their E_a value. The presence of this Asn, however, did appear to stabilize His in its protonated form (ImH⁺) over its unprotonated form (Im). Two novel mechanisms are introduced to explain the unusual effect of a remote X substituent on the deacylation kinetics of the substrate family under consideration. The first mechanism invokes a “field effect” while the second mechanism embodies the concepts of induction and homoconjugation. The unique feature of these two mechanisms is that, unlike other proposed models, they circumvent the requirement for a close N…S interaction which has stimulated controversy.     

Three-dimensional quantitative structure--property relationship (3D-QSPR) models for prediction of thermodynamic properties of polychlorinated biphenyls (PCBs): enthalpy of sublimation

Three-dimensional quantitative structure--property relationship (3D-QSPR) models have been constructed using comparative molecular field analysis (CoMFA) to correlate the sublimation enthalpies at 298.15 K of a series of polychlorinated biphenyls (PCBs) with their CoMFA-calculated physicochemical properties. Various alignment schemes, such as atom fit, as is, and inertial were employed in this study. Separate CoMFA models were developed using different partial charge formalisms, namely, electrostatic potential (ESP) and Gasteiger-Marsili (GM) charges. Among the four different CoMFA models constructed for sublimation enthalpy (Delta(sub)H(m)(298.15 K)), the model that combined atom fit alignment and ESP charges yielded the greatest self-consistency (r(2) = 0.976) and internal predictive ability (r(cv)(2) = 0.750). This CoMFA model was used to predict Delta(sub)H(m)(298.15 K) of PCBs for which the corresponding experimental values are unavailable in the literature.     

Lewis Acid-Promoted, Stereocontrolled, Gram Scale, Diels-Alder Cycloadditions of Electronically Matched 2-Pyrones and Vinyl Ethers: The Critical Importance of Molecular Sieves and the Temperature of Titanium Coordination with the Pyrone

(R)-(+)-Binol-titanium coordinates with commercial methyl 2-pyrone-3-carboxylate and promotes mild, highly enantiocontrolled Diels-Alder cycloadditions with electron-rich vinyl ether CH(2)=CHOCH(2)-1-naphthyl and vinyl silyl ether CH(2)=CHOSiMe(2)Bu-t leading to valuable 1alpha,25-dihydroxyvitamin D(3) (calcitriol) intermediate (-)-2. Unexpectedly, two subtle variables were found to be critical for obtaining reproducibly over 90% enantioselectivities in gram scale cycloadditions: (1) the moisture content (15-17% is best) of the molecular sieves used to prepare the binol-titanium complex according to the Mikami protocol and (2) the temperature (50 degrees C is best) at which the pyrone ester is mixed with the binol-titanium complex. Unsubstituted 2-pyrone undergoes ytterbium-promoted, high-pressure, regioselective, and stereoselective Diels-Alder cycloaddition with benzyl vinyl ether to form versatile bicyclic lactone (+/-)-4 on gram scale.     

Efficacy of DA-7218, a new oxazolidinone prodrug, in the treatment of experimental actinomycetoma produced by Nocardia brasiliensis

Two recently synthesized oxazolidinones: (R)-3-(4-(2-(2-methyltetrazol-5-yl)-pyridin-5-yl)-3-fluorophenyl)-5-hydroxymethyloxazolidin-2-one (DA-7157) and its corresponding pro-drug (R)-3-(4-(2-(2-methyltetrazol-5-yl)-pyridin-5-yl)-3-fluorophenyl)-2-oxo-5-oxazolidinyl) methyl disodium phosphate (DA-7218), have shown very good activity against several Gram positive bacteria, including Nocardia and Mycobacterium. In the present work we evaluated the therapeutic in vivo effects of DA-7218 on Nocardia brasiliensis. We first determined the plasma concentration of the prodrug in BALB/c mice using several doses and then tested its activity in an in vivo experimental actinomycetoma murine model. At the end of treatment, there was a statistically significant difference between the three drug receiving groups (25, 12.5 and 5 mg/kg) and the control group(saline solution) (p=0.001), proving that DA-7218 is effective for the treatment of experimental murine actinomycetoma. This compound could be a potential option for patients affected with mycetoma by Nocardia brasiliensis.     

Poly(ProDOT‐Et2): A High‐Contrast,High‐Coloration Efficiency Electrochromic Polymer

The synthesis and electrochemical polymerization of 3,3‐diethyl‐3,4‐dihydro‐2H‐thieno‐[3,4‐b][1,4]dioxepine (ProDOT‐Et₂) was performed resulting in a stable electrochromic polymer capable of switching between an absorbing blue neutral state and a highly transmissive sky‐blue oxidized state in sub‐second time frames. High optical switching contrast ratios (up to 75% at λ_max) and high composite coloration efficiencies (505 cm²/C) were measured.     

A Bijection Between Paths for the {\mathcal{M}(p, 2p + 1)} Minimal Model Virasoro Characters

The states in the irreducible modules of the minimal models can be represented by infinite lattice paths arising from consideration of the corresponding RSOS statistical models. For the ${\mathcal{M}(p, 2p + 1)}$ models, a completely different path representation has been found recently, this one on a half-integer lattice; it has no known underlying statistical-model interpretation. The correctness of this alternative representation has not yet been demonstrated, even at the level of the generating functions, since the resulting fermionic characters differ from the known ones. This gap is filled here, with the presentation of two versions of a bijection between the two path representations of the ${\mathcal{M}(p, 2p + 1)}$ states. In addition, a half-lattice path representation for the ${\mathcal{M}(p + 1, 2p + 1)}$ models is stated, and other generalisations suggested.     

Accurate density functional theory description of binding constants and NMR chemical shifts of weakly interacting complexes of C60 with corannulene‐based molecular bowls

Density functional calculations on “catch and release” complexes of C₆₀ with corannulene derived molecular bowls show that computationally obtained ¹H nuclear magnetic resonance (NMR) chemical shifts can be used as a reliable predictor of binding constants. A wide range of functionals was benchmarked against accurate ab initio calculations to ensure a credible representation of the weak forces that dominate the interactions in these systems. The most reliable density functional theory (DFT) results were then calibrated using experimentally observed NMR data. Careful analysis and comparison of a wide range of commonly used density functionals shows that the explicit inclusion of dispersion corrections is currently the only reliable way to accurately describe the systems investigated in our study. Moreover, we are able to show that the B97‐D and ωB97X‐D functionals are not only able to reproduce ab initio benchmark calculations, but they do so accurately with a moderately sized basis sets and without the problems of numerical integration we encountered with other functionals in this study. © 2013 Wiley Periodicals, Inc.