Forazoline A: Marine‐Derived Polyketide with Antifungal In Vivo Efficacy

Forazoline A, a novel antifungal polyketide with in vivo efficacy against Candida albicans, was discovered using LCMS‐based metabolomics to investigate marine‐invertebrate‐associated bacteria. Forazoline A had a highly unusual and unprecedented skeleton. Acquisition of ¹³C–¹³C gCOSY and ¹³C–¹⁵N HMQC NMR data provided the direct carbon–carbon and carbon–nitrogen connectivity, respectively. This approach represents the first example of determining direct ¹³C–¹⁵N connectivity for a natural product. Using yeast chemical genomics, we propose that forazoline A operated through a new mechanism of action with a phenotypic outcome of disrupting membrane integrity.     

COADJOINT ORBITS FOR THE CENTRAL EXTENSION OF Diff^＋（S^1） AND THEIR REPRESENTATIVES

According to Kirillov′s idea, the irreducible unitary representations of a Liegroup G roughly correspond to the coadjoint orbits O. In the forward direction one ap-plies the methods of geometric quantization to produce a representation, and in the reversedirection one computes a transform of the character of a representation, to obtain a coad-joint orbit. The method of orbits in the representations of Lie groups suggests the detailedstudy of coadjoint orbits of a Lie group G in the space g* dual to the Lie algebra g of G.In this paper, two primary goals are achieved: one is to completely classify the smoothcoadjoint orbits of Virasoro group for nonzero central charge c; the other is to find repre-sentatives for coadjoint orbits. These questions have been considered previously by Segal,Kirillov, and Witten, but their results are not quite complete. To accomplish this, theauthors start by describing the coadjoint action of D-the Lie group of all orientation pre-serving diffeomorphisms on the circle S^1, and its central extension D~, then the authors willgive a complete classification of smooth coadjoint orbits. In fact, they can be parameterizedby a subspace Of conjugacy classes of PSU~(1,1). Finally, the authors will show how to findrepresentatives of coadjoint orbits by analyzing the vector fields stabilizing the orbits, anddescribe the amazing connection between the characteristic (trace) of conjugacy classes of PSU~(1, 1) and that of vector fields stabilizing orbits.     

A label-free, direct and noncompetitive FRET immunoassay for ochratoxin A based on intrinsic fluorescence of an antigen and antibody complex

A label-free, direct and noncompetitive homogeneous immunoassay, in which ochratoxin A (OTA) coupled with the anti-OTA antibody participates in fluorescence resonance energy transfer (FRET), was developed for the detection of OTA with great specificity and a detection limit of 1 ng mL(-1).     

A review on the interrogation of peptide-metal interactions using electrospray ionization-mass spectrometry

Over the years, protein interactions have been studied by many techniques to obtain a wide breadth of information. The large size and complexity of the macromolecules have caused difficulties for studying them by some techniques. In some cases, peptides, smaller and less complex biomolecules, have been found to be suitable models to mimic the interactions of entire proteins. The study of peptide-metal interaction, in particular, has proven to be fruitful to researchers across the science fields. One technique in particular, electrospray ionization-mass spectrometry (ESI-MS), has been shown to provide a great deal of information to these studies. The speed, sensitivity, and selectivity of MS, along with the information that can be interpreted from MS-based experiments, has driven this technique to the forefront for understanding the nature of peptide-metal complexes. MS has allowed researchers to identify the stoichiometry of peptide-metal complexes or even mixtures of complexes. The specific amino acids in which the metal cations are bound and the degree of association in these complexes can also be determined by MS experiments. The following review discusses the ESI process and how it is ideal for studying noncovalent interactions between peptides and metals. An investigation of the qualitative and quantitative information that has been determined by ESI-MS follows for readers to realize the versatility of this technique and the diversity of information that can be obtained by a variety of related methods.     

Synthesis of substituted pyrazoles via tandem cross-coupling/electrocyclization of enol triflates and diazoacetates

The synthesis of 3,4,5-trisubstituted pyrazoles via a tandem catalytic cross-coupling/electrocyclization of enol triflates and diazoacetates is presented. The initial scope of this methodology is demonstrated on a range of differentially substituted acyclic and cyclic enol triflates as well as an elaborated set of diazoacetates to provide the corresponding pyrazoles with a high degree of structural complexity.     

Aza-crown macrocycles as chiral solvating agents for mandelic acid derivatives

A series of new chiral macrocycles containing the trans-1,2-diaminocyclohexane (DACH) subunit and arene- and oligoethylene glycol-derived spacers has been prepared in enantiomerically pure form. Four of the macrocycles have been characterized by X-ray crystallography, which reveals a consistent mode of intramolecular N-H···N hydrogen bonding and conformational variations about the N-benzylic bonds. Most of the macrocycles were found to differentiate the enantiomers of mandelic acid (MA) by (1)H NMR spectroscopy in CDCl(3); within the series of macrocycles tested, enantiodiscrimination was promoted by (i) a meta-linkage geometry about the arene spacer, (ii) the presence of naphthalene- rather than phenylene-derived arene spacers, and (iii) increasing length of the oligoethylene glycol bridge. (1)H NMR titrations were performed with optically pure MA samples, and the data were fitted to a simultaneous 1:1 and 2:1 binding model, yielding estimates of 2:1 binding constants between some of the macrocycles and MA enantiomers. In several cases, NOESY spectra of the MA:macrocycle complexes show differential intramolecular correlations between protons adjacent to the amine and carboxylic acid groups of the macrocycles and MA enantiomers, respectively, thus demonstrating geometric differences between the diastereomeric intermolecular complexes. The three most effective macrocycles were employed as chiral solvating agents (CSAs) to determine the enantiomeric excess (ee) of 18 MA samples over a wide ee range and with very high accuracy (1% absolute error).     

An efficient and expeditious synthesis of novel 2,2-dialkyl-2,3-dihydrobenzofurans from phenols and 2,2-dialkylacetaldehydes

Reactions of 2,2-dialkylaldehydes with electron-rich 2-naphthols and para-substituted phenols in presence of catalytic amount of $p$ -TSA under closed vessel solvent-free microwave irradiation conditions resulted in formation of corresponding 2,2-dialkyl-1,2-dihydronaphtho[2,1- $b$ ]furans and 2,2-dialkyl-2,3-dihydrobenzofurans, respectively, in good to excellent yields. The effect of stoichiometry, temperature, and catalyst in reaction progress was systematically investigated. 14-Alkyl- $14H$ -dibenzo[ $a,j$ ]xanthenes was obtained as minor products when 2-naphthol and 6-bromo-2-naphthols were used as starting phenols. Simple phenols gave a lower yield of the 2,2-dialkyl-2,3-dihydrobenzofurans products than their electron-rich naphthalene counterparts. Also, xanthene-type products were not detected in case of simple phenols by GC–MS or column chromatography.     

Numerical study of blast characteristics from detonation of homogeneous explosives

A new robust numerical methodology is used to investigate the propagation of blast waves from homogeneous explosives. The gas-phase governing equations are solved using a hybrid solver that combines a higher-order shock capturing scheme with a low-dissipation central scheme. Explosives of interest include Nitromethane, Trinitrotoluene, and High-Melting Explosive. The shock overpressure and total impulse are estimated at different radial locations and compared for the different explosives. An empirical scaling correlation is presented for the shock overpressure, incident positive phase pressure impulse, and total impulse. The role of hydrodynamic instabilities to the blast effects of explosives is also investigated in three dimensions, and significant mixing between the detonation products and air is observed. This mixing results in afterburn, which is found to augment the impulse characteristics of explosives. Furthermore, the impulse characteristics are also observed to be three-dimensional in the region of the mixing layer. This paper highlights that while some blast features can be successfully predicted from simple one-dimensional studies, the growth of hydrodynamic instabilities and the impulsive loading of homogeneous explosives require robust three-dimensional investigation.