A novel strategy for the synthesis of benzofuran skeleton neolignans: application to ailanthoidol,XH-14, and obovaten

A convenient and general approach to the synthesis of the benzofuran skeleton compounds ailanthoidol, XH-14, and obovaten was developed. Starting from vanillin, a series of reactions afforded 7 in 71% yield. Treatment of 7 with n-BuLi followed by addition of substituted benzaldehydes resulted in the formation of carbinols 11 and 31. The substituted benzophenones obtained from oxidation of 11 and 31 were treated with trimethylsilyldiazomethane lithium salt to give diphenylacetylenes 15 and 33, respectively. 15 and 33 were then cyclized in the presence of either mercury acetate in acetic acid or bromine in chloroform to give 3-chloromercurio- or 3-bromobenzofuran, respectively. The 3-chloromercurio intermediates could be reduced to proton or derivatized to ester or bromide, leading to the synthesis of ailanthoidol, XH-14, and obovaten, respectively. In addition, necleophilic substitution was used to introduce a formyl or methyl group into the 3-bromobenzofuran derivatives, providing an alternative pathway to XH-14 and obovaten. The final elongation and deprotection reaction furnished the desired ailanthoidol, XH-14, and obovaten in yields of 30, 15, and 11%, respectively.     

Latrunculins: NMR study,two new toxins and a synthetic approach

A complete ¹H and ¹³C NMR assignment of one of the latrunculins (B) was accomplished with the aid of 2D NMR COSY and CH shift-correlation experiments. The various H-H Coupling constants have been datermined and a conformation of the macrolide and the tetrahydropyran (THP) ring suggested on basis of the J-values and measured NOE's. The absolute configuration of latrunculin-A($\text{1}$) was determined on the grounds of its earlier X-Ray analysis, and a chemical degradation to a known compound. Two novel latrunculins, -C($\text{3}$) and -D($\text{4}$), were isolated from the Red Sea sponge $\text{L. magnifica}$ and their structures elucidated. Starting with L-cysteine a synthon for the latrunculins has been synthesized.     

The stokes and robinson hydration theory: A modification with application to concentrated electrolyte solutions

The proposed extension to the Stokes and Robinson hydration theory is based on the premise that H₂O molecules of electrolyte solutions reside in two unique environments, the solvent environment and the hydration envelope (or sheath) environment. Changes to the chemical potential of H₂O in either environment result in redistribution of H₂O molecules between the environments; consequently hydration numbers of electrolytes decrease as the solvent activity decreases. An equation derived from the theory and containing two adjustable parameters reproduces electrolyte activity coefficients more accurately than does the original Stokes and Robinson equation.     

Innovative detection methods for aquatic algal toxins and their presence in the food chain

Detection of aquatic algal toxins has become critical for the protection of human health. During the last 5 years, techniques such as optical, electrochemical, and piezoelectric biosensors or fluorescent-microsphere-based assays have been developed for the detection of aquatic algal toxins, in addition to optimization of existing techniques, to achieve higher sensitivities, specificity, and speed or multidetection. New toxins have also been incorporated in the array of analytical and biological methods. The impact of the former innovation on this field is highlighted by recent changes in legal regulations, with liquid chromatography–mass spectrometry becoming the official reference method for marine lipophilic toxins and replacing the mouse bioassay in many countries. This review summarizes the large international effort to provide routine testing laboratories with fast, sensitive, high-throughput, multitoxin, validated methods for the screening of seafood, algae, and water samples.     

A pyrone remodeling strategy to access diverse heterocycles: application to the synthesis of fascaplysin natural products

The synthesis of diverse N-fused heterocycles, including the pyrido[1,2-a]indole scaffold, using an efficient pyrone remodeling strategy is described. The pyrido[1,2-a]indole core was demonstrated to be a versatile scaffold that can be site-selectively functionalized. The utility of this novel annulation strategy was showcased in a concise formal synthesis of three fascaplysin congeners.

The synthesis of diverse N-fused heterocycles, including the pyrido[1,2-a]indole scaffold, using an efficient pyrone remodeling strategy is described.     

A unified approach to the chromatography-FTIR interface: GC-FTIR,SFC-FTIR,and HPLC-FTIR with subnanogram detection limits

The results described in this paper demonstrate that Identifiable FTIR spectra of components separated by gas, supercritical fluid, and liquid chromatography can be measured in real time using a common approach. The sensitivity of each Interface is comparable with that obtained by interfacing the corresponding technique with a bench-top mass spectrometer. The combination of these two spectroscopic techniques should lead to an even more powerful means of Identification of volatile, semi-volatile, and non-volatile components of mixtures.     

Pushing the limits of NAA: Accuracy,uncertainty and detection limits

This paper describes some highlights from the author’s efforts to improve neutron activation analysis (NAA) detection limits through development and optimization of radiochemical separations, as well as to improve the overall accuracy of NAA measurements by identifying, quantifying and reducing measurement biases and uncertainties. Efforts to demonstrate the metrological basis of NAA, and to establish it as a “Primary Method of Measurement” will be discussed.     

A computational multiscale strategy to the study of amorphous materials

A first step towards a computational multiscale approach has been adopted here to deal with the computational simulation of the Hench bioglass^® 45S5, an amorphous material of 48.1% SiO₂, 25.9% CaO, 22.2% Na₂O and 3.7% P₂O₅ composition. Molecular dynamics simulations based on classical force fields followed by static minimizations on quenched structures have been run on a unit cell size suitable for subsequent ab initio calculations. The molecular mechanics optimized unit cell envisaging 78 atoms of Na₁₂Ca₇P₂Si₁₃ O₄₄ composition and P1 symmetry has then been fully optimized (both unit cell parameters and internal coordinates) at B3LYP level in a periodic approach using gaussian basis sets of double-ζ quality and the development version of the CRYSTAL03 code. Comparison between the molecular mechanics and B3LYP optimized structures shows the latter to give a slightly higher density than the former, due to overestimation of the Si–O bonds and underestimation of the Si–O–Si and Si–O–P angles, respectively. Other geometrical features are in excellent agreement within the two approaches. Electronic properties of the Hench bioglass have been reported at B3LYP for the first time and both Mulliken charges and electronic band structure show a rather ionic character of the material, whereas a band gap of about 6.5 eV characterizes the bioglass as a strong insulator. Work presently in progress will soon allow the information to be transferred from the B3LYP calculations to the molecular mechanics engine in order to refine the presently available empirical force fields for complex ionic systems and their surfaces.     

A new, iterative strategy for the synthesis of unsymmetrical polyynes: application to the total synthesis of 15,16-dihydrominquartynoic acid

[reaction: see text] A new iterative strategy for the synthesis of unsymmetrically substituted polyynes has been developed. The starting bromoalkyne is homologated by one acetylene unit through palladium-catalyzed cross-coupling with a TIPS-protected terminal acetylene and a subsequent in situ one-pot AgF-mediated desilylative bromination. The utility of this new synthetic method is demonstrated by its application to the total synthesis of (S)-(E)-15,16-dihydrominquartynoic acid.     

Collaborative study for the detection of toxic compounds in shellfish extracts using cell-based assays. Part I: screening strategy and pre-validation study with lipophilic marine toxins

Human poisoning due to consumption of seafood contaminated with phycotoxins is a worldwide problem, and routine monitoring programs have been implemented in various countries to protect human consumers. Following successive episodes of unexplained shellfish toxicity since 2005 in the Arcachon Bay on the French Atlantic coast, a national research program was set up to investigate these atypical toxic events. Part of this program was devoted to fit-for-purpose cell-based assays (CBA) as complementary tools to collect toxicity data on atypical positive-mouse bioassay shellfish extracts. A collaborative study involving five laboratories was conducted. The responses of human hepatic (HepG2), human intestinal (Caco2), and mouse neuronal (Neuro2a) cell lines exposed to three known lipophilic phycotoxins-okadaic acid (OA), azaspiracid-1 (AZA1), and pectenotoxin-2 (PTX2)-were investigated. A screening strategy composed of standard operating procedures and a decision tree for dose-response modeling and assay validation were designed after a round of "trial-and-error" process. For each toxin, the shape of the concentration-response curves and the IC(50) values were determined on the three cell lines. Whereas OA induced a similar response irrespective of the cell line (complete sigmoid), PTX2 was shown to be less toxic. AZA1 induced cytotoxicity only on HepG2 and Neuro2a, but not on Caco2. Intra- and inter-laboratory coefficients of variation of cell responses were large, with mean values ranging from 35 to 54 % and from 37 to 48 %, respectively. Investigating the responses of the selected cell lines to well-known toxins is the first step supporting the use of CBA among the panel of methods for characterizing atypical shellfish toxicity. Considering these successful results, the CBA strategy will be further applied to extracts of negative, spiked, and naturally contaminated shellfish tissues.     

The diethyldithiocarbamate of mercury: composition,structure and analytical application: A heterometric study

0.3–1.2 mg of mercury (= Hg(NO₃)₂) in 20 ml aqueous solution, can be titrated heterometrically with sodium diethyldithiocarbamate (NaCBM).Vice versa, 0.5–1.0 mg NaCBM in 20 ml aqueous solution can be titrated heterometrically with mercuric nitrate.In both cases the error is mostly equal to zero. The insoluble Hg(CBM)₂ is obtained in both cases.     

A general strategy to determine a target DNA sequence of a short peptide: application to a d-peptide.

Short peptides could potentially provide a novel element to read-out DNA sequences from the major groove. However, it is difficult to determine sequence-preference of de novo designed monomeric short peptides. Because DNS-binding affinity and specificity of short peptides are usually much lower than those of native DNA-binding proteins, determining the sequence-preference of short peptides by conventional methods utilized to deduce the target sequence of proteins often produces an unclear outcome. We report here a general strategy to defining the sequence-preference of a DNA-binding short peptide by using the heterodimers. A GCN4 basic region peptide tethers a low-affinity DNA-binding peptide adjacent to a GCN4 binding sequence through the cyclodextrin-adamantane association, thereby increasing local concentration of the low-affinity peptide on degenerated DNA sequences. An increase of the local concentration allows one to select a preferential sequence for the low-affinity DNA binding peptide. The method successfully identified specific sequences of short peptides derived from native DNA-binding proteins. The usefulness of this approach has been demonstrated by identifying preferred DNA targets for a peptide composed only of d-amino acids. The method is potentially applicable not only to artificial peptides, but also to other synthethic ligands.     

Transition-metal bimaleates and their solid solutions: Synthesis,structural, and thermoanalytical study

Transition-metal hydrogen maleates of composition M(C₄H₃O₄)₂ · 4H₂O, where M = Mn, Fe, Co, and Ni, and their solid solutions were synthesized and characterized by X-ray crystallography, IR spectroscopy, mass spectrometry, and thermal analysis. X-ray crystallography and IR spectroscopy showed that both intramolecular and intermolecular H-bonds exist in these compounds. The generation of continuous substitutional solid solutions with cation substitution in these compounds was studied. The thermolysis mechanism was studied for both transition-metal hydrogen maleates and their solid solutions. The composite produced by thermolysis is stable up to 1200°C in flowing helium.     

The polarity of alcoholic electrolyte solutions : A systematic study

The E_T (30) polarity values of alcoholic salt solutions were determined for twenty salt/solvent combinations. In all cases equation [2] correlates accurately the medium polarity with the salt concentration. The meaning of this equation is discussed in terms of possible interactions in solution. The dye (1) is shown to be a useful probe for the cationic environment of salts in solution.     

A new water-soluble chromogenic indicator: an application to the determination of chlorine in aqueous solutions.

A novel compound, N,N'-bis(2,4-di-sulfobenzyl)tolidine tetrasodium salt (SBT), was synthesized for use as a chromogenic indicator for oxidizing substances, and its applicability to the colorimetric determination of chlorine in water was examined.     

Polarographic determination of hydroxylamines: application to analysis of photographic processing solutions

Procedures for the determination of hydroxylamine and N,N-diethylhydroxyIamine (DEHA), based on anodic polarographic waves, are described. The importance of using a strongly alkaline supporting electrolyte and of complete removal of dissolved oxygen is illustrated. With rapid alternating current (a.c.) polarography, 3 × 10^-6 M hydroxylamine and 4 × 10^-5 M DEHA can be detected. Detection limits with the differential pulse technique are approximately tenfold lower. In a practical application, rapid a.c. polarography is shown to be suitable for the direct determination of hydroxylamine and DEHA in photographic processing solutions. The only pretreatment of samples is dilution with a strongly alkaline supporting electrolyte. Possible interferences from other constituents of the processing solutions are avoided by using the standard addition method.