Stereoisomers of P. aeruginosa autoinducer analog to probe the regulator binding site.
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Quorum sensing (QS) regulates the production of virulence factors and the maturation of biofilms in many bacteria, including Pseudomonas aeruginosa. The QS cascade is activated by the interaction of bacterial signaling molecules, called autoinducers (AIs), with their corresponding regulatory proteins. Here, we report a series of studies to define the stereochemical preferences of synthetic agonists and perform docking studies to understand the microenvironment of the binding site in P. aeruginosa QS regulators. One of the key findings of this work is that the ring structure and the absolute and relative stereochemistries of the amide and hydroxyl groups dictate the agonist activity. This study aids in determining important structural and stereochemical characteristics necessary for interaction with the QS regulatory proteins, thus expanding our understanding of their inducer binding sites. (+info)
A direct catalytic asymmetric Mannich-type reaction via a dinuclear zinc catalyst: synthesis of either anti- or syn-alpha-hydroxy-beta-amino ketones.
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The use of imines bearing a hydrolyzable nitrogen substituent in direct asymmetric Mannich reactions with alpha-hydroxyketones is developed. Previous work focused on the use of N-arylimines or nonenolizable imines, and the latter with only methoxy-substituted alpha-hydroxyacetophenones. Using a dinuclear catalyst devised from 2,6-di-(S)-2'-diphenylhydroxymethylpyrrolidino-N-methyl)-4-methylphenol and diethylzinc, a broad array of hydroxyacetylated aromatics, including phenyl, 2-furyl, 1-naphthyl, and 2-naphthyl, react well. In addition, the reactions focused on the use of enolizable imines. With the N-diphenylphosphinoyl, the reactions are anti selective with enantiomeric excesses ranging from 83 to 99%, except for the reaction of the 2-methoxy-2'-hydroxyacetylbenzene. With the N-Boc-imines, the reactions were syn selective with enantiomeric excesses from 90 to 94%. The dependence of the diastereoselectivity on the nature of the N-substituent presumably arises from the steric demands of the diphenylphosphinoyl group. (+info)
Applications of deactivated GC columns for analysis of nitrogen-containing chemicals related to the chemical weapons convention.
(19/233)
Nitrogen-containing chemicals are one of the important families of compounds relevant to the purposes of the Chemical Weapons Convention (CWC). Several applications, using various injection modes, of new deactivated columns specially designed for basic compounds are presented. These columns prove remarkably well-suited to the gas chromatographic (GC) analysis of the chemicals of interest, even to underivatized amino-alcohols, whose analysis on conventional GC columns is often difficult and hindered by poor resolution and high detection limits. Such a deactivated phase can even replace the typical GC phases used for CWC verification purposes. (+info)
Probing nitrogen-sensitive steps in the free-radical-mediated deamination of amino alcohols by ethanolamine ammonia-lyase.
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The contribution of C-N bond-breaking/making steps to the rate of the free-radical-mediated deamination of vicinal amino alcohols by adenosylcobalamin-dependent ethanolamine ammonia-lyase has been investigated by 15N isotope effects (IE's) and by electron paramagnetic resonance (EPR) spectroscopy. 15N IE's were determined for three substrates, ethanolamine, (R)-2-aminopropanol, and (S)-2-aminopropanol, using isotope ratio mass spectrometry analysis of the product ammonia. Measurements with all three substrates gave measurable, normal 15N IE's; however, the IE of (S)-2-aminopropanol was approximately 5-fold greater than that of the other two. Reaction mixtures frozen during the steady state show that the 2-aminopropanols give EPR spectra characteristic of the initial substrate radical, whereas ethanolamine gives spectra consistent with a product-related radical (Warncke, K.; Schmidt, J. C.; Kee, S.-C. J. Am. Chem. Soc. 1999, 121, 10522-10528). The steady-state concentration of the radical with (R)-2-aminopropanol is about half that observed with the S isomer, and with (R)-2-aminopropanol, the steady-state level of the radical is further reduced upon deuteration at C1. The results show that relative heights of kinetic barriers differ among the three substrates such that levels or identities of steady-state intermediates differ. 15N-sensitive steps are significant contributors to V/K with (S)-2-aminopropanol. (+info)
Preliminary evaluation of interactions between selected alcoholamines and model skin sebum components.
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The aim was to evaluate the interaction between selected alcoholamines and components of artificial skin sebum. The rate and depth of penetration into the lipophilic bead imitating pilosebaceous unit lumen was applied for alcoholamine penetration activity assay. The activity differentiation of 0.5% aqueous alcoholamine solutions with a potential cleansing effect on the pilosebaceous unit was performed. The depth of aminomethylpropanol penetration increased from 0.080 mm after 15 min to 3.049 mm after 72 h. The depth of aminomethylpropendiol penetration increased with time from 0.148 to 4.064, respectively, of diisopropanolamine from 0.481 to 4.626, triethanolamine from 0.236 to 4.342, triisopropanolamine from 0.275 to 2.392 and trometamol from 0.338 to 4.580. The products of alcoholamines reaction with the model skin sebum are easily dispersed in water. The rate of alcoholamines reaction with the model skin sebum depends on the alcoholamine, being the highest in the case of diisopropanolamine, decreasing to minimum for triisopropanolamine. Selected alcoholamines would be applied in ex vivo and in vivo research. (+info)
A convenient preparation of (1R,2S,7S,8R)-3,5-diaza-2,7-dimethyl-1,8-diphenyloctan-1,8-diol and its enantiomer.
(22/233)
The synthesis of (1R,2S,7S,8R)-3,5-diaza-2,7-dimethyl-1,8-diphenyloctan-1,8-diol 6 and its enantiomer 7 are described utilising (-)-(1R,2S)- or (+)-(1S,2R)-norephedrine, respectively. (+info)
Enantioselective fluorescent recognition of amino alcohols by a chiral tetrahydroxyl 1,1'-binaphthyl compound.
(23/233)
The tetrahydroxyl derivative of BINOL, (S)- or (R)-1, and its analogues are synthesized. (S)- or (R)-1 can be used to conduct the enantioselective recognition of chiral amino alcohols. In comparison with BINOL, the two additional hydroxyl groups of (S)- or (R)-1 have increased the binding of this compound with the amino alcohols and significantly improved the fluorescence quenching efficiency. The fluorescence responses of (S)- or (R)-1 toward amino alcohols are compared with those of its analogues (R)-4 and (R)-6. It shows that the interaction of the central naphthyl hydroxyl groups of (S)- or (R)-1 with the substrates is responsible for the observed fluorescence quenching, and the two additional alkyl hydroxyl groups increase the quenching efficiency. (+info)
Allergy evaluation after emergency treatment: anaphylaxis to the over-the-counter medication clobutinol.
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Anaphylaxis is traditionally diagnosed and treated as an acute emergency but should be always followed by a search for specific triggers, resulting in avoidance strategies. This case report highlights the relevance of a detailed evaluation after anaphylaxis for diagnosis of a rare but potentially life-threatening allergy. Considering the high frequency of clobutinol application, IgE-mediated allergic hypersensitivity seems extremely rare and has to be distinguished from infection-associated urticaria and angioedema as well as non-specific summation effects. Accidental re-exposure has to be strictly avoided and therefore after identification of clobutinol as the anaphylaxis trigger, the patient received detailed allergy documents including international non-proprietary and trade names of the culprit drug. (+info)