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Carboxylic Acid Derivatives (carboxylic + acid_derivative)
Selected AbstractsEnantioselective Preparation of 2-Aminomethyl Carboxylic Acid Derivatives: Solving the ,2 -Amino Acid Problem with the Chiral Auxiliary 4-Isopropyl-5,5-diphenyloxazolidin-2-one (DIOZ).HELVETICA CHIMICA ACTA, Issue 6 2003Preliminary Communication Multigram amounts of suitably protected ,2 -amino acids with 17 of the 20 proteinogenic side chains are prepared by diastereoselective reactions of Li, B, or Ti enolates of the corresponding 3-acyl-4-isopropyl-5,5-diphenyloxazolidin-2-ones (acyl-DIOZ; 1) with appropriate electrophiles (amidomethylation, hydroxyalkylation, (benzyloxycarbonyl)methylation) in yields of 55,90% and with diastereoselectivities of 80 to >97% (Scheme). The primary products 2,8 thus obtained are converted to protected ,2 -amino acids by standard procedures (Table,1). Many of the DIOZ derivatives are highly crystalline compounds (31 X-ray crystal structures in Table,2). The chiral auxiliary DIOZ, readily prepared in either enantiomeric form, is recovered with high yield. [source] ChemInform Abstract: Solvent- and Catalyst-Free gem-Bisallylation of Carboxylic Acid Derivatives with Allylzinc Bromide.CHEMINFORM, Issue 3 2009Yu-Juan Wei Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Highly Regio- and Stereoselective Asymmetric Bromoazidation of Chiral ,,,-Unsaturated Carboxylic Acid Derivatives: Scope and Limitations.CHEMINFORM, Issue 12 2007Saumen Hajra Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Dynamic Kinetic Resolution of ,-Bromo Carboxylic Acid Derivatives in Asymmetric Nucleophilic Substitution with Chiral ,-Amino Esters.CHEMINFORM, Issue 47 2005Ji-yeon Chang Abstract For Abstract see ChemInform Abstract in Full Text. [source] Synthesis and 11C-labelling of (E,E)-1-(3,,4,-dihydroxystyryl)-4-(3,-methoxy-4,-hydroxystyryl) benzene for PET imaging of amyloid deposits,,JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 8 2002Yanming Wang Abstract Carboxylic acid derivatives of the amyloid-binding dye Congo red do not enter the brain well and are thus unable to serve as in vivo amyloid-imaging agents. A neutral amyloid probe, (E,E)-1-(3,,4,-dihydroxystyryl)-4-(3,-methoxy-4,-hydroxystyryl)benzene (3), devoid of any carboxylate groups has been designed and synthesized via a 12-step reaction sequence with a total yield of 30%. The unsymmetric compound 3 has also been labelled with C-11 via [11C]methyl iodide ([11C]CH3I) methylation of a symmetric 4,4,-dimesyl protected precursor followed by deprotection. Preliminary evaluation indicated that compound 3 selectively stained plaques and neurofibrillary tangles in post-mortem AD brain, and exhibited good binding affinity (Ki=38±8 nM) for A,(1,40) fibrils in vitro. In vivo pharmacokinetic studies indicated that [11C]3 exhibited higher brain uptake than its carboxylic acid analogs and good clearance from normal control mouse brain. [11C]3 also exhibited specific in vivo binding to pancreatic amyloid deposits in the NOR-beta transgenic mouse model. These results justify further investigation of 3 and similar derivatives as surrogate markers for in vivo quantitation of amyloid deposits. Copyright © 2002 John Wiley & Sons, Ltd. [source] Rufinamide: Clinical pharmacokinetics and concentration,response relationships in patients with epilepsyEPILEPSIA, Issue 7 2008Emilio Perucca Summary Rufinamide is a new, orally active antiepileptic drug (AED), which has been found to be effective in the treatment of partial seizures and drop attacks associated with the Lennox-Gastaut syndrome. When taken with food, rufinamide is relatively well absorbed in the lower dose range, with approximately dose-proportional plasma concentrations up to 1,600 mg/day, but less than dose-proportional plasma concentrations at higher doses due to reduced oral bioavailability. Rufinamide is not extensively bound to plasma proteins. During repeated dosing, steady state is reached within 2 days, consistent with its elimination half-life of 6,10 h. The apparent volume of distribution (Vd/F) and apparent oral clearance (CL/F) are related to body size, the best predictor being body surface area. Rufinamide is not a substrate of cytochrome P450 (CYP450) enzymes and is extensively metabolized via hydrolysis by carboxylesterases to a pharmacologically inactive carboxylic acid derivative, which is excreted in the urine. Rufinamide pharmacokinetics are not affected by impaired renal function. Potential differences in rufinamide pharmacokinetics between children and adults have not been investigated systematically in formal studies. Although population pharmacokinetic modeling suggests that in the absence of interacting comedication rufinamide CL/F may be higher in children than in adults, a meaningful comparison of data across age groups is complicated by age-related differences in doses and in proportion of patients receiving drugs known to increase or to decrease rufinamide CL/F. A study investigating the effect of rufinamide on the pharmacokinetics of the CYP3A4 substrate triazolam and an oral contraceptive interaction study showed that rufinamide has some enzyme-inducing potential in man. Findings from population pharmacokinetic modeling indicate that rufinamide does not modify the CL/F of topiramate or valproic acid, but may slightly increase the CL/F of carbamazepine and lamotrigine and slightly decrease the CL/F of phenobarbital and phenytoin (all predicted changes were <20%). These changes in the pharmacokinetics of associated AEDs are unlikely to make it necessary to change the dosages of these AEDs given concomitantly with rufinamide, with the exception that consideration should be given to reducing the dose of phenytoin. Based on population pharmacokinetic modeling, lamotrigine, topiramate, or benzodiazepines do not affect the pharmacokinetics of rufinamide, but valproic acid may increase plasma rufinamide concentrations, especially in children in whom plasma rufinamide concentrations could be increased substantially. Conversely, comedication with carbamazepine, vigabatrin, phenytoin, phenobarbital, and primidone was associated with a slight-to-moderate decrease in plasma rufinamide concentrations, ranging from a minimum of ,13.7% in female children comedicated with vigabatrin to a maximum of ,46.3% in female adults comedicated with phenytoin, phenobarbital, or primidone. In population modeling using data from placebo-controlled trials, a positive correlation has been identified between reduction in seizure frequency and steady-state plasma rufinamide concentrations. The probability of adverse effects also appears to be concentration-related. [source] New Pentadentate Carboxylate-Derivatized Sulfur Ligands Affording Water Soluble Iron Complexes with [Fe(NS4)] Cores that Bind Small Molecules (CO, NO, PMe3) as Co-LigandsEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 3 2004Dieter Sellmann Abstract In the search for polydentate sulfur ligands that are able to form water-soluble iron complexes which can bind nitrogenase relevant molecules, the new pentadentate ligands pyCO2MeS4,H2 [2,6-bis[2-mercapto-3-(methoxycarbonyl)phenylthio]dimethylpyridine] (1) and pyCO2HS4,H2 [2,6-bis(2-mercapto-3-carboxyphenylthio)dimethylpyridine] (2) having NS4 donor atom sets and terminal thiolate donors have been synthesized. The starting material was CO2MeS2,H2 (2,3-dimercapto benzoic acid methyl ester) which was alkylated with 2,6-bis[(tosyloxy)methyl]pyridine. The problem of specifically achieving regioselective mono-alkylation of this 1,2-benzene-dithiol derivative was solved by carrying out the alkylation of CO2MeS2,H2 at ,78 °C in the presence of stoichiometric amounts of a base. Saponification of 1 afforded the carboxylic acid derivative. Coordination of pyCO2MeS42, to FeII in the presence of co-ligands (L = CO, PMe3) yielded the complexes [Fe(L)(pyCO2MeS4)] where L = CO (5) or PMe3 (4). Upon treatment with NOBF4, complex 5 afforded [Fe(NO)(pyCO2MeS4)]BF4 (7) which could be subsequently converted to the isolable 19 valence electron species [Fe(NO)(pyCO2MeS4)] (8) upon reduction with N2H4. In the absence of potential co-ligands, coordination of pyCO2MeS42, to FeII afforded the dinuclear complex [Fe(pyCO2MeS4)]2 (6) whilst coordination to NiII gave [Ni(pyCO2MeS4)]x (3). Solubility of these complexes in water could be achieved by replacing the CO2Me groups with CO2H substituents. The ligand pyCO2HS42, afforded the iron complexes [Fe(L)(pyCO2HS4)] [L = CO (10) and PMe3 (12)] and [Fe(NO)(pyCO2HS4)]BF4 (11). Both 10 and 12 could be reversibly deprotonated to give the corresponding water-soluble salts (NMe4)2[Fe(L)(pyCO2S4)] with L = CO {(NMe4)2 [9]} and PMe3 {(NMe4)2 [13]}. The complexes were characterized by elemental analysis, spectroscopic methods and X-ray structural determinations. The molecular structure of [Fe(PMe3)(pyCO2HS4)] (12) was found to exhibit inter- and intramolecular O,H···O and O,H···S hydrogen bonds which serve as models for proton transfer steps from external sources to the active sites of metal sulfur enzymes. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source] Efficient One-Step Synthesis of Benzazoles in Aqueous MediaEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 29 2009Hassan Zali Boeini Abstract Benzazoles (benzoxazoles, benzothiazoles, and benzimidazoles) were efficiently prepared by the aquatic reaction of the corresponding thioamidinium salts and 2-aminophenol, 2-aminothiophenol, and 1,2-diaminobenzene, respectively. The thioamidinium salt was successfully applied as an alternative to a carboxylic acid derivative to react smoothly with an amino precursor and in the presence of catalytic amounts of hexadecyltrimethylammonium bromide salt to produce benzazoles in good to excellent yields.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Oxidative metabolism by Thalassiosira weissflogii (Bacillariophyceae) of a diol-ester of okadaic acid, the diarrhetic shellfish poisoningJOURNAL OF PHYCOLOGY, Issue 2 2000Anthony J. Windust Previous investigations into the comparative toxicity of the diarrhetic shellfish poisoning (DSP) toxins to Thalassiosira weissflogii (Grun.) Fryxell et Hasle found that this diatom oxidatively metabolized okadaic acid diol-ester (OA diol-ester) to a more water-soluble product. This oxidative transformation of OA diol-ester by the diatom is significant for two reasons. First, it is known that dinophysistoxin-4 (DTX-4), the primary DSP toxin produced by the dinoflagellate Exuviaella lima (Ehr.) Butschli, will be hydrolyzed to the diol-ester following cell rupture (e.g. ingestion by a predator). Second, it implies that the ester, an uncharged, lipophilic intermediate, can easily enter cells and therefore may play an important role in the uptake and transfer of DSP toxins through the food web. It has been suggested that the water soluble DTX-4 may also be the form in which DSP toxins are excreted from the producing cell. Therefore, the stability of DTX-4 was examined when incubated either in fresh seawater medium into which washed cells of E. lima were introduced or in seawater medium conditioned by E. lima cells. Rapid hydrolysis of DTX-4 to the diol-ester took place in both cases. Thus, regardless of the route by which DTX-4 is liberated from the cell, either by cell disruption or excretion, the diol-ester will be the dominant form of the toxin to challenge associated organisms. To examine the metabolism of OA diol-ester by T. weissflogii in more detail, serial cultures of the diatom were challenged with OA diol-ester at a concentration of 2.0 ,g·mL,1. The metabolism and fate of the diol-ester in both cellular and medium fractions were monitored over 3 days using liquid chromatography with either ultraviolet (LC-UV) or mass spectrometric (LC-MS) detection. During the course of the experiment, all of the diol-ester was metabolized. LC-MS analysis revealed the presence of multiple oxidative products of OA diol-ester in the medium fraction, including a carboxylic acid derivative. The major metabolites were isolated in sufficient quantity to permit structural elucidation by NMR and MS. All the metabolites identified resulted from oxidation of the diol-ester side chain with the primary sites of attack at the terminal, subterminal, and unsaturated carbons. OA was found in both cellular and medium fractions, and its production was directly correlated with the metabolism of the diol-ester. The relative partitioning of both OA diol-ester and its oxidation products between cells and medium supports the contention that OA diol-ester can readily enter cells, be metabolized, and then excreted in more water-soluble forms. [source] Metabolism of olaquindox in rat liver microsomes: structural elucidation of metabolites by high-performance liquid chromatography combined with ion trap/time-of-flight mass spectrometry,RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 7 2008Zhaoying Liu Olaquindox (N -(2-hydroxyethyl)-3-methyl-2-quinoxalincarboxamide-1,4-dioxide) is a growth-promoting feed additive for food-producing animals. Its toxicity is closely related to the metabolism. The complete metabolic pathways of olaquindox are not revealed. To improve studies of the metabolism and toxicity of olaquindox, its biotransformation in rat liver microsomes and the structure of its metabolites using high-performance liquid chromatography combined with ion trap/time-of-flight mass spectrometry (LC/MS-ITTOF) were investigated. When olaquindox was incubated with an NADPH-generating system and rat liver microsomes, ten metabolites (M1,M10) were detected. The structures of these metabolites were identified from mass spectra and comparison of their changes in their accurate molecular masses and fragment ions with those of the parent drug. With the high resolution and good mass accuracy achieved by this technique, the elemental compositions of the metabolites and their fragment ions were exactly determined. The results indicate that the N,,,O group reduction is the main metabolic pathway of olaquindox metabolism in rat liver microsomes, because abundant 1-desolaquindox (M2), 4-desolaquindox (M1) and bisdesoxyolaquindox (M9) were produced during the incubation step. Seven other minor metabolites were revealed which were considered to be hydroxylation metabolites, based on the position of the quinoxaline ring or 3-methyl group and a carboxylic acid derivative on the side chain at position 2 of the quinoxaline ring. Among the identified metabolites, five new hydroxylated metabolites (M3,M7) were found for the first time in rat liver microsomes. This work will conduce to complete clarification of olaquindox metabolism, and improve the in vivo metabolism of olaquindox in food animals. Copyright © 2008 John Wiley & Sons, Ltd. [source] Manganese-Promoted Regioselective Ring-Opening of 2,3-Epoxy Acid Derivatives: A New Route to ,-Hydroxy Acid DerivativesADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 13 2009Abstract A simple and general methodology directed towards the synthesis 3-aryl-2-hydroxy amides, or esters with total regioselectivity from the easily available 2,3-epoxy amides or esters, promoted by active manganese is described. Utilizing enantiopure epoxy amides as starting materials, the corresponding 3-aryl-2-hydroxy amides in enantiopure form are also available. Some synthetic applications of selected examples of 3-aryl-2-hydroxy carboxylic acid derivatives are shown. A mechanism has been proposed to explain this novel reaction. [source] Tetrahedral intermediates in reactions of carboxylic acid derivatives with nucleophiles,JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 3 2005Martin Adler Abstract Transacylation reactions of carboxylic acids, carboxylic acid esters, carboxylic acid amides and other carboxylic acid derivatives are among the most widespread and most important reactions in chemistry and biochemistry. Already in 1887, Claisen suggested a tetrahedral intermediate in transformations of carboxylic acid derivatives with nucleophiles. A historical overview gives insight into the studies to detect possible tetrahedral intermediates in such reactions. However, only in recent years has detailed information concerning the structures of such species become available. In this review, neutral, cationic and anionic tetrahedral intermediates are described which serve as models for transacylations under neutral, acid-catalysed or basic conditions. The characteristically different structures correspond nicely with experimental experience with reactions of carboxylic acid derivatives and with quantum chemical model calculations on tetrahedral intermediates. Finally, by means of model calculations, an explanation is given for the fast reactions of Weinreb amides, RC(O)N(CH3)OCH3, with organolithium and even with Grignard reagents: the reactions are determined by comparatively stable chelate transition states. Copyright © 2004 John Wiley & Sons, Ltd. [source] Influence of Structure on Polymerization Rates and Ca-Binding of Phosphorus-Containing 1,6-DienesMACROMOLECULAR REACTION ENGINEERING, Issue 5 2007Aylin Ziylan Albayrak Abstract Photo- and thermal-polymerizations of 4-diethoxyphosphoryl-2,4,6-tris(ethoxycarbonyl)-1,6-heptadiene, 4,4-bis(diethoxyphosphoryl)-2,6-bis(t -butoxycarbonyl)-1,6-heptadiene and 4-diethoxyphosphoryl-4-ethoxycarbonyl-2,6-bis(t -butoxycarbonyl)-1,6-heptadiene monomers and their phosphonic and carboxylic acid derivatives were investigated to understand the effect of the cyclic monomer structure on their polymerization reactivity. A strong effect of the substituents at positions 2, 4 and 6 of the monomers on polymerization rate was observed. The polymerizability of the monomers was successfully correlated with the 13C NMR chemical shifts of the vinyl carbons. Conversion values were consistent with the Tg being a measure of the flexibility of a monomer. The monomers containing phosphonic acid groups were soluble in water and ethanol. The acidic nature of the aqueous solutions of these monomers is expected to give them etching properties, important for dental applications. The interaction of the acid monomers with hydroxyapatite was investigated using 13C NMR technique. [source] Derivatisation for liquid chromatography/electrospray mass spectrometry: synthesis of pyridinium compounds and their amine and carboxylic acid derivativesRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 6 2003Samantha J. Barry A simple method has been developed for the pre-column derivatisation of low molecular weight primary and secondary amines and carboxylic acids using quaternary nitrogen compounds to enhance their detection by liquid chromatography/electrospray ionisation mass spectrometry (LC/ESI-MS). The synthesis of seven novel quaternary nitrogen reagents is described. The derivatives are designed to be relatively small molecules to avoid some of the steric hindrance problems that may be associated with larger derivatisation reagents. The compounds have amine and carboxylic acid functional groups with which to derivatise carboxylic acids and amines, respectively. Two of the compounds contain a bromine atom in order to assess the advantages of a bromine isotope pattern in the mass spectra. This acts as a simple marker for derivatisation and enables data processing by cluster analysis. Activation of the carboxylic acid group was achieved by the use of either 1-chloro-4-methylpyridinium iodide (CMPI) or the more reactive 1-fluoro-4-methylpyridinium p -toluenesulphonate (FMP).1 Using both of these active reagents, the degree of nucleophilic substitution was investigated for the derivatisation of a variety of small molecules. Whilst giving some increase in the ESI-MS response for the derivatised compounds, the FMP itself acted as a derivatising reagent in a competing reaction. In the light of this finding, FMP was reacted with the test compounds separately and gave positive results as a derivatising reagent. Detection of the ,pre-charged' derivatives of amines and carboxylic acids by LC/ESI-MS was investigated with respect to their ESI response and chromatography. Copyright © 2003 John Wiley & Sons, Ltd. [source] Nitrilase and Its Application as a ,Green' CatalystCHEMISTRY & BIODIVERSITY, Issue 12 2006Ram Singh Abstract Hydrolase-catalyzed reactions have been widely applied in organic synthesis. Nitrilases are an important class of hydrolase that converts naturally occurring, as well as xenobiotically derived, nitriles to the corresponding carboxylic acids and ammonia. Because of their inherent enantio- and regioselectivities and other benefits, nitrilases are attractive as ,green', mild, and selective catalysts for setting stereogenic centers in fine-chemical synthesis and enantiospecific synthesis of a variety of carboxylic acid derivatives. In this review, the literature has been surveyed to provide a comprehensive coverage of the application of nitrilases in organic synthesis. Literature has also been cited to describe the isolation and/or characterization of nitrilases and related enzymes. [source] Electroluminescent Diodes from Complementary Discotic BenzoperylenesCHEMPHYSCHEM, Issue 9 2003Sonia Alibert-Fouet Dr. Unequal brothers: Benzoperylene carboxylic acid derivatives with flexible chains not only form charge-transporting columnar liquid crystals (see graphic), their charge-transport properties can also be tuned to be either of n - or of p -type: relatively minor changes in the substitution pattern yield different materials that are complementary enough to form red-fluorescent charge-transfer complexes and p,n junction electronic devices. [source] | |||||||||||||