Stereoselective total syntheses and reassignment of stereochemistry of the freshwater cyanobacterial hepatotoxins cylindrospermopsin and 7-epicylindrospermopsin

A stereoselective total synthesis of the structure 1 proposed for the freshwater cyanobacterial heptatotoxin cylindrospermopsin has been accomplished in approximately 30 operations starting from commercially available 4-methoxypyridine. Utilizing methodology developed by Comins, the tetrasubstituted piperidine A-ring unit of the hepatotoxin was efficiently constructed. The two remaining stereocenters in the natural product were then set by a stereospecific intramolecular N-sulfinylurea Diels-Alder cyclization/Grignard ring opening/allylic sulfoxide [2,3]-sigmatropic rearrangement sequence previously developed in these laboratories, leading to key intermediate 29. The stereochemical assignment of alcohol 29, which contains all six of the stereogenic centers of the natural product, was confirmed by an X-ray crystal structure determination of a derivative. Installation of the D-ring uracil moiety was effected by using our new methodology developed for this purpose, and construction of the C-ring guanidine completed the total synthesis of racemic structure 1. However, the (1)H NMR data for this compound do not match that of cylindrospermopsin, but instead agree with the data reported for 7-epicylindrospermopsin, a minor toxic metabolite that co-occurs with cylindrospermopsin. Therefore, we propose a revision of the stereochemical assignments of these natural products such that cylindrospermopsin is now represented as structure 2 and 7-epicylindrospermopsin is 1. This reassignment was further confirmed by Mitsunobu inversion of the C-7 alcohol 51 to epimer 52, and conversion of this compound to tetracyclic diol 57, which has previously been transformed to cylindrospermopsin (2).     

Mass spectrometric investigation of bimolecular compounds

Two points involving molecular structure have been investigated using mass spectrometry. First, mass spectra have been obtained that indicate a rapid means for differentiating bimolecular compounds from other structural isomers. Second, the mass spectrometric method has been used to evaluate bonding within bimolecular compounds. Quinone compounds have been reacted with dhydroxybenzene compounds to produce quinhydrone products, and upon mass spectrometric analysis, the quinhydrones decompose to regenerate derivatives of the starting materials. Evaluation of the decomposition products suggests that the hydroxyl hydrogens are involved in a resonance structure, and while in symmetrical quinhydrones, the hydroxyl hydrogens are probably associated equally with each reactant, unsymmetrical quinhydrones generate an unbalanced electronic distribution that eliminates the complete equivalency of the hydrogens.     

The set of mapsF_{a,b} :x \mapsto x + a + \tfrac{b}{{2\pi }} sin(2πx) with any given rotation interval is contractiblewith any given rotation interval is contractible

Consider the two-parameter family of real analytic maps $F_{a,b} :x \mapsto x + a + \tfrac{b}{{2\pi }}$ sin(2πx) which are lifts of degree one endomorphisms of the circle. The purpose of this paper is to provide a proof that for any closed intervalI, the set of mapsF _a,b whose rotation interval isI, form a contractible set.     

A sensitivity comparison of three photoacoustic cells containing a single microphone,a differential dual microphone or a cantilever pressure sensor

Three photoacoustic (PA) cells designed for trace-gas sensing were compared by measuring absorption by the P(15) rotational line of the vibrational combination band of acetylene using a distributed-feedback diode laser. Normalised sensitivities were determined for each cell by analysis of the signal to noise ratios of acquired spectra. The first cell was constructed in-house, and contained a single electret microphone held in a stainless steel tube. The second cell was a differential PA cell that contained two microphones housed in identical flow tubes, with one microphone to detect the PA signal and the other to determine background noise levels. The third cell contained a novel cantilever pressure sensor, movement of which was measured by a compact laser interferometer. Normalised sensitivities (2σ) of 3.1×10^-7, 1.7×10^-7 and 2.2×10^-9 cm^-1 W Hz^-1/2, respectively, were obtained. An erbium-doped fibre amplifier was used to amplify the laser power, and a detection limit of 9.8×10¹⁰ molecule cm^-3 was obtained using the cantilever pressure sensor PA cell, with a laser power of 1.17 W. This detection limit corresponded to a mixing ratio of 14.5 parts per billion by volume at 277 mbar. PACS 82.80.Kq; 42.62.Fi; 82.80.Gk     

Mechanism of amine catalyzed isomerization of itaconic anhydride to citraconic anhydride: Citraconamic acid formation

The amine catalyzed isomerization of itaconic to citraconic anhydride has been investigated. Studies show that the rate of isomerization is dependent on the base strength and solvent media. Triethylamine causes complete isomerization within 5 min at room temperature in acetone or chloroform solvent, whereas aromatic tertiary amines such as pyridine and N,N-dimethylaniline require time perods as long as 23h at room temperature for almost complete isomerization. In the presence of aniline no isomerization occures even under acetone reflux conditions over a 24 h period. For the preparation of citraconamic acids from itaconic anhydrides and aliphatic diamines nuclear magnetic resonance and infrared spectroscopic evidence is presented to support the reaction path of initial isomerization of itaconic anhydride to citraconic anhydride followed by amine attack on the anhydride to form the corresponding cis-citraconamic acids. The mechanism of isomerization of itaconic to citraconic acids is proposed.     

Negative thermal expansion in ZrW2O8: mechanisms, rigid unit modes, and neutron total scattering

The local structure of the low-temperature ordered phase of the negative thermal expansion (NTE) material has been investigated by reverse Monte Carlo (RMC) modeling of neutron total scattering data. We obtain, for the first time, quantitative measurements of the extent to which the and polyhedra move as rigid units, and we show that these values are consistent with the predictions of rigid unit mode theory. We suggest that rigid unit modes are associated with the NTE. Our results do not support a recent interpretation of x-ray-absorption fine structure spectroscopy data in terms of a larger rigid structural component involving the Zr-O-W linkage.     

Phonons from powder diffraction: a quantitative model-independent evaluation

We describe a model-independent approach for the extraction of detailed lattice dynamics information from neutron powder diffraction data, based on a statistical analysis of atomistic configurations generated using reverse Monte Carlo structural refinement. Phonon dispersion curves for MgO extracted in this way are shown to reproduce many of the important features found in those determined independently using neutron triple-axis spectroscopy. By means of molecular dynamics simulations, we quantify the extent to which the diffraction data are sensitive to lattice dynamics in this system.     

Manipulations of listeners' echo perception are reflected in event-related potentials

To gain information from complex auditory scenes, it is necessary to determine which of the many loudness, pitch, and timbre changes originate from a single source. Grouping sound into sources based on spatial information is complicated by reverberant energy bouncing off multiple surfaces and reaching the ears from directions other than the source's location. The ability to localize sounds despite these echoes has been explored with the precedence effect: Identical sounds presented from two locations with a short stimulus onset asynchrony (e.g., 1-5 ms) are perceived as a single source with a location dominated by the lead sound. Importantly, echo thresholds, the shortest onset asynchrony at which a listener reports hearing the lag sound as a separate source about half of the time, can be manipulated by presenting sound pairs in contexts. Event-related brain potentials elicited by physically identical sounds in contexts that resulted in listeners reporting either one or two sources were compared. Sound pairs perceived as two sources elicited a larger anterior negativity 100-250 ms after onset, previously termed the object-related negativity, and a larger posterior positivity 250-500 ms. These results indicate that the models of room acoustics listeners form based on recent experience with the spatiotemporal properties of sound modulate perceptual as well as later higher-level processing.