Beckmann Rearrangement of Cyclotriveratrylene (CTV) Oxime: Tandem Beckmann-Electrophilic Aromatic Addition

The Beckmann rearrangement has been performed on the oxime of cyclotriveratrylene (CTV) with thionyl chloride affording the ring-expanded 10-membered ring amide exclusively in high yield. Modified conditions afford a helical pentacycle derived from an unusual tandem Beckmann rearrangement and electrophilic aromatic addition followed by demethylation and tautomerization

Metal-Free Tandem Beckmann–Electrophilic Aromatic Substitution Cascade Affording Diaryl Imines, Ketones, Amines, and Quinazolines

A cascade reaction sequence involving a Beckmann rearrangement on benzophenone oxime followed by an electrophilic aromatic substitution (EAS) on the intermediate nitrilium ion affords N-phenyl diaryl imines that may then be hydrolyzed to ketones, or reduced to the corresponding amines. Reaction with benzonitrile afforded 2,4-diphenylquinazoline through a Beckmann–Ritter–EAS cascade

A Thermodynamic and Kinetic Characterization of the Solvent Dependence of the Saddle-Crown Equilibrium of Cyclotriveratrylene (CTV) Oxime

The equilibration of the saddle conformer of cyclotriveratrylene (CTV) oxime to the corresponding crown conformer was followed by (1)H NMR in five separate solvents, and kinetic and thermodynamic parameters were determined from the NMR data. The oxime saddle conformers of 3 are favored in CDCl(3) (K(eq) = [saddle]/[crown] = 1.4), whereas the CTV oxime crown conformer 3a is favored in three more polar solvents studied (DMSO-d(6), acetonitrile-d(3), acetone-d(6)). Surprisingly, the CTV oxime crown conformer is also slightly favored in the nonpolar solvent 1,4-dioxane-d(8). These behaviors are discussed in terms of hydrogen bonding, entropy, and possible host-guest considerations. An X-ray crystal structure was obtained for CTV monoketone, and structures of the different conformers of CTV, CTV ketone, and CTV oxime were calculated with semiempirical AM1 methods for direct comparison of their ground-state energies

A High Throughput Workflow Environment for Cosmological Simulations

The next generation of wide-area sky surveys offer the power to place extremely precise constraints on cosmological parameters and to test the source of cosmic acceleration. These observational programs will employ multiple techniques based on a variety of statistical signatures of galaxies and large-scale structure. These techniques have sources of systematic error that need to be understood at the percent-level in order to fully leverage the power of next-generation catalogs. Simulations of large-scale structure provide the means to characterize these uncertainties. We are using XSEDE resources to produce multiple synthetic sky surveys of galaxies and large-scale structure in support of science analysis for the Dark Energy Survey. In order to scale up our production to the level of fifty 10^10-particle simulations, we are working to embed production control within the Apache Airavata workflow environment. We explain our methods and report how the workflow has reduced production time by 40% compared to manual management.Comment: 8 pages, 5 figures. V2 corrects an error in figure

Rearrangement of Cyclotriveratrylene (CTV) Diketone: 9,10-Diarylanthracenes with OLED Applications

Electroluminescent 9,10-diaryl anthracenes have been shown to be promising host and hole-transporting materials in organic electroluminescence due to their high thermal stability, electrochemical reversibility, and wide band gap useful for organic light-emitting diodes (OLEDs), especially blue OLEDs. Oxidation of cyclotriveratrylene (CTV) to the corresponding diketone and subsequent bromination resulted in an unexpected rearrangement to a highly functionalized 9-aryl-10-bromoanthracene derivative, which was employed in Suzuki couplings to synthesize a series of 9,10-diaryl compounds that are structural analogues of anthracene derivatives used in the preparation of OLEDs but are more highly functionalized, including electron-donating methoxy groups in addition to substitution by a carboxylic acid moiety. The UV/fluorescence solution spectra show strong emissions at 446, 438, and 479 nm, respectively, for the anthracene 10-phenyl, 10-naphthyl, and 10-pyrenyl adducts containing a benzoic acid functional group, whereas the analogues bearing the hydroxymethylene moiety from reduction of the benzoic acid to the corresponding alcohols gave much shorter emission wavelengths of 408, 417, and 476 nm, respectively, and had somewhat higher quantum yields, suggesting they are better candidates for OLED applications

Practical Spectrophotometric Assay for the \u3cem\u3edapE\u3c/em\u3e-Encoded \u3cem\u3eN\u3c/em\u3e-Succinyl-L,L-Diaminopimelic Acid Desuccinylase, a Potential Antibiotic Target

A new enzymatic assay for the bacterial enzyme succinyl-diaminopimelate desuccinylase (DapE, E.C. 3.5.1.18) is described. This assay employs N6-methyl-N2-succinyl-L,L-diaminopimelic acid (N6-methyl-L,L-SDAP) as the substrate with ninhydrin used to detect cleavage of the amide bond of the modified substrate, wherein N6-methylation enables selective detection of the primary amine enzymatic product. Molecular modeling supported preparation of the mono-N6-methylated-L,L-SDAP as an alternate substrate for the assay, given binding in the active site of DapE predicted to be comparable to the endogenous substrate. The alternate substrate for the assay, N6-methyl-L,L-SDAP, was synthesized from the tert-butyl ester of Boc-L-glutamic acid employing a Horner-Wadsworth-Emmons olefination followed by an enantioselective reduction employing Rh(I)(COD)(S,S)-Et-DuPHOS as the chiral catalyst. Validation of the new ninhydrin assay was demonstrated with known inhibitors of DapE from Haemophilus influenza (HiDapE) including captopril (IC50 = 3.4 [± 0.2] μM, 3-mercaptobenzoic acid (IC50 = 21.8 [±2.2] μM, phenylboronic acid (IC50 = 316 [± 23.6] μM, and 2-thiopheneboronic acid (IC50 = 111 [± 16] μM. Based on these data, this assay is simple and robust, and should be amenable to high-throughput screening, which is an important step forward as it opens the door to medicinal chemistry efforts toward the discovery of DapE inhibitors that can function as a new class of antibiotics

Carborane‐Containing Matrix Metalloprotease (MMP) Ligands as Candidates for Boron Neutron‐Capture Therapy (BNCT)

Based on the previously reported potent and selective sulfone hydroxamate inhibitors SC‐76276, SC‐78080 (SD‐2590), and SC‐77964, potent MMP inhibitors have been designed and synthesized to append a boron‐rich carborane cluster by employing click chemistry to target tumor cells that are known to upregulate gelatinases. Docking against MMP‐2 suggests binding involving the hydroxamate zinc‐binding group, key H‐bonds by the sulfone moiety with the peptide backbone residues Leu82 and Leu83, and a hydrophobic interaction with the deep P1’ pocket. The more potent of the two triazole regioisomers exhibits an IC50 of 3.7 nM versus MMP‐2 and IC50 of 46 nM versus MMP‐9

Isolation of the Saddle and Crown Conformers of Cyclotriveratrylene (CTV) Oxime

The oxime of cyclotriveratrylene (CTV) has been prepared and the individual crown and saddle conformers were isolated and characterized. The equilibrium constant was measured in CDCl3 and in DMSO-d6 and was shown to favor the crown conformer by an order of magnitude in DMSO-d6, relative to an approximately equal mixture at equilibrium in CDCl3. The time course for interconversion of the saddle to the crown was measured by 1H NMR and the t1/2 of the saddle was determined to be 2.45 h in CDCl3 at 25 °C, and 3.71 h in DMSO-d6

Cyclobutanone Inhibitor of Cobalt-Functionalized Metallo-γ-Lactonase AiiA with Cyclobutanone Ring Opening in the Active Site

An α-amido cyclobutanone possessing a C10 hydrocarbon tail was designed as a potential transition-state mimetic for the quorum-quenching metallo-γ-lactonase autoinducer inactivator A (AiiA) with the support of in-house modeling techniques and found to be a competitive inhibitor of dicobalt(II) AiiA with an inhibition constant of Ki = 0.007 ± 0.002 mM. The catalytic mechanism of AiiA was further explored using our product-based transition-state modeling (PBTSM) computational approach, providing substrate-intermediate models arising during enzyme turnover and further insight into substrate–enzyme interactions governing native substrate catalysis. These interactions were targeted in the docking of cyclobutanone hydrates into the active site of AiiA. The X-ray crystal structure of dicobalt(II) AiiA cocrystallized with this cyclobutanone inhibitor unexpectedly revealed an N-(2-oxocyclobutyl)decanamide ring-opened acyclic product bound to the enzyme active site (PDB 7L5F). The C10 alkyl chain and its interaction with the hydrophobic phenylalanine clamp region of AiiA adjacent to the active site enabled atomic placement of the ligand atoms, including the C10 alkyl chain. A mechanistic hypothesis for the ring opening is proposed involving a radical-mediated process

Desempenho forrageiro de híbridos de Paspalum obtidos por meio de cruzamentos interespecíficos

The goal of this study was to assess the variability of Paspalum plicatulum x P. guenoarum interspecific hybrids in terms of agronomic performance and their tolerance to cold conditions, as well as to estimate the correlation of different phenotypic characters associated with forage production. Twenty hybrids plants were used, besides one access P. guenoarum, one of P. plicatulum and the cultivar ‘Pensacola’ (P. notatum). Assessments were performed on individual plants, in a completely randomized design with five repetitions. Paspalum genotypes presented variability in total dry matter, leaf dry mass, leaf: stem ratio, and tolerance to cold. We suggest selection of the hybrids 08Q01 and 08Q44 for new stages within a forage improvement program. Estimates of phenotypic correlation may aid in the selection of genotypes with better agronomic traits.O objetivo deste estudo foi avaliar a variabilidade de híbridos interespecíficos de Paspalum plicatulum x P. guenoarum por meio do desempenho agronômico e tolerância ao frio, bem como estimar as correlações fenotípicas de diferentes caracteres ligados à produção de forragem. Foram utilizados 20 híbridos, um acesso de P. guenoarum, um de P. plicatulum e a cultivar ‘Pensacola’ (P. notatum). As avaliações foram realizadas em plantas individuais, em delineamento completamente casualizado, com cinco repetições. Os genótipos de Paspalum apresentam variabilidade para massa seca total, massa seca de folhas e relação folha: colmo e na tolerância ao frio. É possível selecionar os híbridos 08Q01 e 08Q44 para novas etapas dentro de um programa de melhoramento de forrageiras. As estimativas de correlações fenotípicas podem auxiliar na seleção de genótipos com caracteres agronômicos superiores