Total synthesis of alternariol

Total synthesis of alternariol, a toxic secondary metabolite of various Alternaria fungi, was achieved in seven steps starting with orcinol and 3,5-dimethoxybromobenzene. The longest linear sequence consists of six steps. Key reaction is a palladium-catalyzed Suzuki-type coupling of an orcinol-derived boronic acid with a brominated resorcylic aldehyde. The final demethylation furnished alternariol in 73% yield containing a smaller fraction of alternariol 9-methyl ether (approximately 20%).     

Liquid chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry of the Alternaria mycotoxins alternariol and alternariol monomethyl ether in fruit juices and beverages

Alternariol (AOH) and alternariol monomethyl ether (AME) are among the main mycotoxins formed in apples and other fruits infected by Alternaria alternata. For determination of AOH and AME by LC, apple juice and other fruit beverages were cleaned up on C18 and aminopropyl solid-phase extraction columns. Positive and negative ion mass spectra of AOH and AME under electrospray (ESI) and atmospheric pressure chemical ionization (APCI) conditions were obtained. Collision-induced dissociation of the [M+H]+ and [M-H]- ions for both compounds were also studied. The phenolic anions of both compounds are more stable with less fragmentation. In quantitative analysis, negative ion detection also offers lower background and better sensitivity. Sensitive LC-MS and LC-MS-MS confirmatory procedures based on APCI with negative ion detection were applied to confirm the natural occurrence of AOH in nine samples of apple juice and in single samples of some other clear fruit beverages--grape juice, cranberry nectar, raspberry juice, red wine, and prune nectar (which also contained 1.4 ng AME/ml)--at levels of up to 6 ng AOH/ml. Electrospray LC-MS-MS with negative ion detection and in multiple reaction monitoring mode offers higher sensitivity and specificity. Absolute detection was better than 4 pg per injection for both compounds.     

A new alternariol glucoside from fungus Alternaria alternate cib-137

A new secondary metabolite, 2-O-methylalternariol 4-O-β-[4-methoxyl-glucopyranoside] (1), together with four known compounds alternariol methyl ether (2), altenuene (3), isoaltenuene (4) and 2-(2′S-hydroxypropyl)-5-methyl-7-hydroxychromone (5), was isolated from the fungus Alternaria alternate cib-137. Its structure was elucidated on the basis of spectroscopic data. Compounds 3 and 4 demonstrated moderate activity against Staphylococcus aureus.     

Improvement of alternariol monomethyl ether detection at gold electrodes modified with a dodecanethiol self-assembled monolayer

The electro-oxidation of alternariol monomethyl ether (AME), one of the main metabolites of the Alternaria genus mycotoxins, is studied at 1-dodecanethiol (DDT)-modified gold electrodes, in acetonitrile (ACN) – aqueous phosphate buffer solutions of different pH values, by using cyclic (CV) and square-wave (SWV) voltammetries. The AME voltammetric response at the bare electrode suffers from two drawbacks: it appears at potentials close to the onset of gold oxide formation, and it is hampered by a fouling of the electrode surface due to the accumulation of oxidized products. These shortcomings are circumvented by the use of DDT-coated electrodes, since the intervening monolayer inhibits gold oxide formation and surface passivation by the electrochemical products, without affecting the oxidation kinetics of AME significantly. Diagnostic criteria based on the voltammetric peak parameters show that the electrochemical behavior of AME at the modified electrode is mainly controlled by reactant diffusion from solution, with a weak adsorption of both the mycotoxin and its oxidation products at monolayer defects. Calibration curves were constructed from the AME square-wave voltammetric response and a detection limit of 9.1 × 10⁻⁸ mol dm⁻³ was determined, which is about three times smaller than a previous estimate at platinum and glassy carbon electrodes, and about fifty times smaller than the limit derived from measurements carried out at a polyphenol oxidase-modified carbon paste electrode.     

Determination of alternariol in tomato paste using solid phase extraction and high-performance liquid chromatography with fluorescence detection.

Alternaria spp. produce a wide variety of toxic metabolites with different chemical structures. Tomato products have been considered a likely source of Alternaria toxins in the human diet because Alternaria is an important spoilage mold of tomatoes. A new method for the determination of these mycotoxins in tomato paste, involving solid phase cartridges for extraction before HPLC fluorescence detection with a reversed phase column and isocratic elution, was developed. The method was demonstrated to be linear in the range 5.2-196 ppb of alternariol (AOH) in tomato paste. Good recoveries were obtained for AOH at all levels assayed (minimum 77.2%). The detection limit of the AOH toxin in real samples of tomato paste was low, 1.93 ppb. The precision of the method was demonstrated with a good repeatability (RSD = 2.98%) and reproducibility (RSD = 9.35%).     

Isolation, structure elucidation, and mutagenicity of four alternariol derivatives produced by the mangrove endophytic fungus No. 2240

A new alternariol derivative, 2240B (1), together with alternariol (2), alternariol 4,10-dimethyl ether (3), and alternariol 4-methyl ether (4), was isolated from the ethyl acetate extract of the liquid medium GYT of No. 2240, the mangrove endophytic fungus from the South China Sea Coast. The structure of compound 1 was unambiguously elucidated as alternariol 4-methyl-10-acethyl ester by spectra including one/two-dimensional NMR, HREIMS, IR, and UV. The structures of compounds 2–4 were also established by spectroscopic analyses and comparison with related literature data. The anticancer tests showed that compounds 2 and 4 had strong activities against KB and KBv200 cells with IC₅₀ values of 3.17, 3.12, and 4.82, 4.94 μg/mL, while compounds 1 and 3 exhibited weak activities against the two kinds of tumor lines with IC₅₀ values of more than 50 μg/mL. Published in Khimiya Prirodnykh Soedinenii, No. 3, pp. 235–238, May–June, 2008.     

A simple,highly sensitive colorimetric immunosensor for the detection of alternariol monomethyl ether in fruit by non-aggregated gold nanoparticles

Analytical and Bioanalytical Chemistry - Alternariol monomethyl ether (AME) is one of the major Alternaria mycotoxins present in a wide range of fruits, vegetables, grains, and their products, and...     

Total synthesis of masked Alternaria mycotoxins—sulfates and glucosides of alternariol (AOH) and alternariol-9-methyl ether (AME)

The synthesis of different protected alternariol derivatives using intramolecular cyclization of iodoresorcylic acid phenyl esters by palladium-catalyzed C–H activation as key step is presented. Furthermore, chemical sulfation and glucosylation were applied for the preparation of conjugated Alternaria mycotoxins. These compounds are suspected to be formed during metabolism in contaminated plants. Therefore, all synthetic conjugates prepared within this work serve as reference materials for further studies in the fields of bioanalytics and toxicology of mycotoxins.     

Combined Kalman filtering and steepest descent minimization for quantitative analysis of unresolved misaligned chromatographic peaks. The resolution of alternariol and altenuisol mycotoxins in mixtures by HPLC

Summary The potential of a computational approach for the quantitative resolution of seriously overlapping chromatographic peaks when there is loss of collinearity between the pure component peaks and the mixture peak has been explored. The program makes iterative use of the Kalman filter algorithm for resolving the mixture peak with the component peaks aligned according to some values of the position parameters, and of a steepest descent minimization procedure to find the optimal alignment. This combined procedure has been applied to the quantitive resolution of the HPLC chromatograms of alternariol and altenuisol mycotoxins in synthetic mixtures and in real samples.     

Dichroism of absorption and polarization of phosphorescence of molecules of the closed form of nitrobenzospirothiopyran

The spectral-polarization characteristics of absorption and phosphorescence of molecules of the initial form of nitro-substituted indolinospirobenzothiopyran were studied in oriented polyethylene films and in solutions with different polarity. An oscillator model of the electron transitions responsible for the formation of absorption and luminescence spectra was suggested. It was established that the principal differences in the spectral and photophysical properties of the compound studied and its oxygen-containing analog are associated with the fact that the electronegativity of the S atom is lower than that of the O atom. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1143–1146, June, 1997.     

Determination of heats of detonation and influence of components of composite explosives on heats of detonation of high explosives

The heats of detonation of 20 simple high explosives and explosive mixtures were determined by means of an adiabatic detonation calorimeter designed by the authors. The results indicated that the performance of the instrument was reliable and the experimental data were very accurate. For explosive mixtures, there was a linear accumulative relationship between the heats of detonation of the explosive mixture and its components. Accordingly, the heats of detonation of explosive mixtures could be calculated directly from the heats of detonation of simple explosives and the characteristic heats of other components. The experiments showed that the gold or brass shell of the cylindrical charge could be substituted by a thick-walled porcelain shell, which had the advantage of cheapness.

     

Effect of the Method of Modification of Zeolite X on Selectivity of Catalytic Methylation of Toluene

Theoretical and Experimental Chemistry - The effect of the method of modification of catalysts based on zeolite X by cesium and magnesium cations (ion exchange and impregnation) on the selectivity...     

非那雄胺合成工艺改进

非那雄胺能抑制5α-还原酶的活性,明显降低二氢睾酮水平,是一种治疗良性前列腺增生的有效药品。该合成工艺以甾烯酮酸为原料,将其与氯化亚砜反应,无须分离即与叔丁胺反应得17β-酰胺化合物,再氧化开环,环合,氢化,脱氢合成了非那雄胺。经元素分析、IR、1HNMR、13CNMR、MS分析表征了其结构。该法无须使用昂贵的2,2-二吡啶二硫化物和剧毒药品苯亚硒酸酐,且以乙酸铵代替氨气,降低了对设备的要求和腐蚀,更适用于工业生产。     

Calculation of enthalpies of hydrogenation of hydrocarbons

Sets of hydrogen molecule equivalents have been developed which permit the calculation of hydrogenation of different types of carbon-carbon bonds from ab initio total energies (3-21G and 6-31G* basis sets, and, to a more limited extent, for MP2/6-31G* data) of reactants and products. The calculated enthalpies of hydrogenation are in good agreement with experiment for unstrained molecules, with average errors on the order of 2 kcal/mol. The 6-31G* equivalents allow the enthalpies for strained molecules to be calculated accurately, but the 3-21G equivalents do not. The equivalents for both basis sets have been tested by calculating the enthalpies of hydrogenation of carbon-carbon bonds in nitrogen- and oxygen-containing organic molecules, free radicals, and classical carbocations. The results are in good agreement with experiment in most cases.     

Influence of viscosity of medium on processes of oxygen quenching of excited states of mesoporphyrin

The oxygen quenching rate constants for singlet and triplet excited states of the dimethyl ester of mesoporphyrin IX increase with decreasing viscosity of the medium and reach a maximum at a viscosity of approximately 0.4 mPa·sec, after which the rate constants begin to decrease. The drop in rate constant with increasing fluidity of the medium may be related to a nonequilibrium character of the elementary act in the interaction of the reactants in the solvent cage. In viscous media such as isopropyl alcohol, isobutyl alcohol, and isoamyl alcohol, the reaction radius is greater than the sum of the radii of the reacting particles. The long-range character of these processes is due to the relatively weak dependence of the quenching probability on distance.Translated from Teoreticheskaya i Éksperimental'naya Khimiya, Vol. 25, No. 2, pp. 161–167, March–April, 1989.     

Calorimetry of dissolution of peganine methyl iodide and calculation of the standard enthalpy of formation of a number of its analogs

Catalytic thermal destruction of ethylenediaminetetraacetic acid and its complexes with nickel, iron, and cobalt in nitrate solutions on carbon materials (activated unwoven material, sibunite, and BAU–A activated carbon) was studied. The activation energies of thermal destruction were calculated.     

Synthesis of phenolic components of Grains of Paradise

Two vanilloids, (5E)-8-(4-hydroxy-3-methoxyphenyl)oct-5-en-4-one (1) and 4-[3-hydroxydecyl]-2-methoxyphenol (2), isolated from the dried seeds of Grains of Paradise (Aframomum melegueta), were synthesized; the latter compound was made as the S-enantiomer and the material derived from the seeds was found to be a 1:1.7 mixture of the R and S isomers. The synthetic route used should allow the preparation of analogs having extended alkyl chains and consequently different lipophilicity, and 3, a homolog of 2, was also prepared.     

Thermodynamics of the formation of oxosulfides of rare-earth elements

The enthalpies of solution of several oxosulfides of rare-earth elements and the high-temperature enthalpies of oxosulfides and oxosulfates of lanthanum and yttrium were measured using solution calorimetry and high-temperature microcalorimetry techniques. Standard enthalpies of formation and some thermodynamic properties of oxosulfides and oxosulfates were calculated. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2 pp. 294–297, February, 1997.