Hydroalumination of seleno acetylenes: a versatile generation and reactions of alpha-aluminate vinyl selenide intermediates in the highly regio and stereoselective synthesis of telluro(seleno)ketene acetals

The hydroalumination of butylseleno acetylenes with DIBAL-H followed by addition of n-butyllithium generated in situ the (Z)-butylseleno vinyl alanates intermediates which were captured with C(4)H(9)TeBr furnishing the (E)-telluro(seleno)ketene acetals exclusively. The isomers with opposite stereochemistry (Z)-telluro(seleno)ketene acetals were obtained by the reduction of phenylseleno acetylenes with lithium di-(isobutyl)-n-butyl aluminate hydride (Zweifel's reagent) followed by reaction of (E)-phenylseleno vinyl alanates intermediates with C(4)H(9)TeBr. (c) 2008 Elsevier Ltd. All rights reserved.

Computational investigation of a stereoselective synthesis of atropisomeric hydrazides possessing an N–N stereogenic axis

Axially chiral substrates are an interesting and widely studied class of compounds as they can be found in bioactive natural products and are employed as functional materials or as ligands in asymmetric catalytic processes. One branch of this family is the well-known world of the atropisomers. Among them, atropisomeric compounds possessing an N–N stereogenic axis are one truthfully fascinating system but not completely understood yet. In this thesis, we computationally investigated the mechanism of the diastereoselective formation of the N – N chiral axis of a hydrazide under asymmetric phase transfer catalytic conditions. Moreover, during this study, torsional barriers have been calculated for both the reagent and the product at the density functional theory (DFT). These values turned out to suitably match the experimental values and observations. Finally, Electronic Circular Dichroism (ECD) spectra have been simulated in order to assign the chiral absolute configuration to the products.

The Total Synthesis Of (-)-cryptocaryol A.

A stereoselective total synthesis of (-)-cryptocaryol A () is described. Key features of the 17-step route include the use of three boron-mediated aldol reaction-reduction sequences to control all stereocenters and an Ando modification of the Horner-Wadsworth-Emmons olefination that permitted the installation of the Z double bond of the α-pyrone ring.

Alilação e crotilação catalítica e enantiosseletiva de aldeídos

The field of chiral catalysis has experienced explosive growth over the last two decades. By now, many of the classical reactions in organic synthesis can be carried out efficiently in asymmetric manner. As one of the fundamental and powerful C-C bond-forming reactions, enantioselective catalytic allylation (ECA) and crotylation (ECC) of aldehydes has attracted considerable attention. In this article, we present an overview about the importance of chiral Lewis acids and bases in catalytic enantioselective addition of allyl- and crotyl metals to aldehydes and the application of this methodology in the total synthesis of natural and non-natural products.

Enzymatic Resolution of Racemic Sulcatol by Lipase from Candida Antarctica in a Large Scale

Large scale enzymatic resolution of racemic sulcatol 2 has been useful for stereoselective biocatalysis. This reaction was fast and selective, using vinyl acetate as donor of acyl group and lipase from Candida antarctica (CALB) as catalyst. The large scale reaction (5.0 g, 39 mmol) afforded high optical purities for S-(+)-sulcatol 2 and R-(+)-sulcatyl acetate 3, i.e., ee > 99 per cent and good yields (45 per cent) within a short time (40 min). Thermodynamic parameters for the chemoesterification of sulcatol 2 by vinyl acetate were evaluated. The enthalpy and Gibbs free energy values of this reaction were negative, indicating that this process is exothermic and spontaneous which is in agreement with the reaction obtained enzymatically.

Synthesis of seleno-carbohydrates derived from D-galactose

The synthesis of seleno-galactopyranosides in a short and efficient manner is described, starting from the parent carbohydrate D-galactose. The approach described allows the synthesis of small libraries of compounds with a number of structural variations at the group attached to selenium. Compounds with aryl, propargyl, allyl, acyl, and alkyl substituents are described. (C) 2010 Elsevier Ltd. All rights reserved.

Synthesis of 5 `-seleno-xylofuranosides

The synthesis of selenium derivatives of naturally occurring chiral molecules is becoming increasingly important in recent years. In this context, we describe herein an easy, straightforward synthetic route for the preparation of a series of chiral seleno-furanosides, starting from the readily available carbohydrate D-xylose. In addition, selected compounds were screened as inhibitors of the delta-aminolevulinate dehyclratase (delta-ALA-D) enzyme. Diselenide 4 was found to reduce significantly the enzymatic activity, while seleno-furanoside la increased delta-ALA-D activity. (C) 2010 Elsevier Ltd. All rights reserved.

Highly efficient palladium-catalyzed Suzuki-Miyaura reactions of potassium aryltrifluoroborates with 5-iodo-1,3-dioxin-4-ones in water: an approach to alpha-aryl-beta-ketoesters

The high efficient palladium-catalyzed Suzuki-Miyaura reactions of potassium aryltrifluoroborates 3 with 5-iodo-1,3-dioxin-4-ones 2a-b in water as only solvent in the presence of n-Bu(4)NOH as base is reported. The respective 5-aryl-1,3-dioxin-4-ones 4a-n were obtained in good to excellent yields. The catalyst system provides high efficiency at low load using electronically diverse coupling partners. The obtained 2,2,6-trimethyl-5-aryl-1,3-dioxin-4-ones were transformed into corresponding alpha-aryl-beta-ketoesters 6 by reaction with an alcohol in the absence of solvent. (C) 2009 Elsevier Ltd. All rights reserved.

Synthesis of selenium- and tellurium-containing nucleosides derived from uridine

The synthesis of selenium- and tellurium-containing nucleosides, derived from uridine is described herein. These compounds were prepared in a concise and short synthetic route in good yields, by nucleophilic substitution of a tosylate group by organoselenium nucleophiles. (C) 2009 Elsevier Ltd. All rights reserved.

Homocoupling reactions of alkynes, alkenes and alkyl compounds

FAPESP[07/5904-2]

Synthesis of potassium and tetra n-butylammonium 2-substituted-1,3-dithianotrifluoroborate salts and addition to chiral cyclic N-acyliminium ions

The synthesis of potassium 2-substituted-1,3-dithianotrifluoroborate salts and tetra-n-butyl ammonium derivatives is described. The reaction proceeds under mild reaction conditions and the corresponding products were obtained in moderate to good yields. The reactivity of these compounds in rections with chiral cyclic N-acyliminium ions was evaluated.

Enantioselective analysis of zopiclone and its metabolites in plasma by liquid chromatography/tandem mass spectrometry

A high-performance liquid chromatographic method with triple-quadrupole mass spectrometry detection (LC-MS-MS) was developed and validated for the first time for the simultaneous quantification of zopiclone and its metabolites in rat plasma samples. The analytes were isolated from rat plasma by liquid-liquid extraction and separated using a chiral stationary phase based on an amylose derivative, Chiralpak ADR-H column, and ethanol-methanol-acetonitrile (50:45:5, v/v/v) plus 0.025% diethylamine as the mobile phase, at a flow-rate of 1.0 mL min(-1). Moclobemide was used as the internal standard. The developed method was linear over the concentration range of 7.5-500 ng mL(-1). The mean absolute recoveries were 74.6 and 75.7; 61.6 and 56.9; 72.5, and 70.7 for zopiclone enantiomers, for N-desmethyl zopiclone enantiomers and for zopiclone-N-oxide enantiomers, respectively, and 75.9 for the internal standard. Precision and accuracy were within acceptable levels of confidence (<15%). The method application in a pilot study of zopiclone kinetic disposition in rats showed that the levels of (+)-(S)-zopiclone were always higher than those of (-)-R-zopiclone. Higher concentrations were also observed for (+)-(S)-N-desmethyl zopiclone and (+)-(S)-N-oxide zopiclone, confirming the stereoselective disposition of zopiclone.

LC-MS-MS determination of ibuprofen, 2-hydroxyibuprofen enantiomers, and carboxyibuprofen stereoisomers for application in biotransformation studies employing endophytic fungi

The purpose of this study was the development and validation of an LC-MS-MS method for simultaneous analysis of ibuprofen (IBP), 2-hydroxyibuprofen (2-OH-IBP) enantiomers, and carboxyibuprofen (COOH-IBP) stereoisomers in fungi culture medium, to investigate the ability of some endophytic fungi to biotransform the chiral drug IBP into its metabolites. Resolution of IBP and the stereoisomers of its main metabolites was achieved by use of a Chiralpak AS-H column (150 x 4.6 mm, 5 mu m particle size), column temperature 8 degrees C, and the mobile phase hexane-isopropanol-trifluoroacetic acid (95: 5: 0.1, v/v) at a flow rate of 1.2 mL min(-1). Post-column infusion with 10 mmol L(-1) ammonium acetate in methanol at a flow rate of 0.3 mL min(-1) was performed to enhance MS detection (positive electrospray ionization). Liquid-liquid extraction was used for sample preparation with hexane-ethyl acetate (1:1, v/v) as extraction solvent. Linearity was obtained in the range 0.1-20 mu g mL(-1) for IBP, 0.05-7.5 mu g mL(-1) for each 2-OH-IBP enantiomer, and 0.025-5.0 mu g mL(-1) for each COOH-IBP stereoisomer (r >= 0.99). The coefficients of variation and relative errors obtained in precision and accuracy studies (within-day and between-day) were below 15%. The stability studies showed that the samples were stable (p > 0.05) during freeze and thaw cycles, short-term exposure to room temperature, storage at -20 degrees C, and biotransformation conditions. Among the six fungi studied, only the strains Nigrospora sphaerica (SS67) and Chaetomium globosum (VR10) biotransformed IBP enantioselectively, with greater formation of the metabolite (+)-(S)-2-OH-IBP. Formation of the COOH-IBP stereoisomers, which involves hydroxylation at C3 and further oxidation to form the carboxyl group, was not observed.

Quantification of chlorpheniramine maleate enantiomers by ultraviolet spectroscopy and chemometric methods

Chlorpheniramine maleate (CLOR) enantiomers were quantified by ultraviolet spectroscopy and partial least squares regression. The CLOR enantiomers were prepared as inclusion complexes with beta-cyclodextrin and 1-butanol with mole fractions in the range from 50 to 100%. For the multivariate calibration the outliers were detected and excluded and variable selection was performed by interval partial least squares and a genetic algorithm. Figures of merit showed results for accuracy of 3.63 and 2.83% (S)-CLOR for root mean square errors of calibration and prediction, respectively. The ellipse confidence region included the point for the intercept and the slope of 1 and 0, respectively. Precision and analytical sensitivity were 0.57 and 0.50% (S)-CLOR, respectively. The sensitivity, selectivity, adjustment, and signal-to-noise ratio were also determined. The model was validated by a paired t test with the results obtained by high-performance liquid chromatography proposed by the European pharmacopoeia and circular dichroism spectroscopy. The results showed there was no significant difference between the methods at the 95% confidence level, indicating that the proposed method can be used as an alternative to standard procedures for chiral analysis.