- Lipase from Carica papaya latex presents high enantioselectivity toward the resolution of prodrug (R,S)-2-bromophenylacetic acid octyl ester
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Besides the well-known papain, lipolytic activity is another interesting enzymatic activity present in latex from Carica papaya. This lipolytic activity is strongly attached to the latex solid phase, resulting in a naturally immobilized biocatalyst. In this work we describe the kinetic resolution of (R,S)-2-bromophenylacetic acid octyl ester by Carica papaya crude latex and two partially purified latex fractions. Several parameters, such as substrate concentration and solvent effects were studied. The best results were obtained using decane as solvent with 50 mM of substrate and 50 mg/mL enzyme/reaction medium; under these conditions, a high enantioselectivity (E >200) was obtained with crude latex. A twofold increase of the initial rate maintaining E >200 was obtained using purified fractions without protease and without esterase. Lipase from Carica papaya latex is the most enantioselective wild-type enzyme ever described for the studied reaction.
- Rivera, Ivanna,Mateos, Juan Carlos,Marty, Alain,Sandoval, Georgina,Duquesne, Sophie
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p. 5523 - 5526
(2013/09/23)
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- Synthesis of enantiomerically enriched-bromonitriles from amino acids
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Two methods were investigated for the preparation of six chiral-bromonitriles with different optic purities. The nitrous deamination of amino acids gives-bromoacids, which react with chlorosulfonyl isocyanate followed by triethylamine to afford-bromonitriles with moderate enantiomeric excess. However, the dehydration of corresponding-bromoamids using thionyl chloride gives-bromonitriles with good enantiomeric excess up to 94%. The use of phosphoryl chloride instead of thionyl chloride results in more than 30% racemization as determined by high-performance liquid chromatograpic analysis.
- Tka, Najeh,Kraem, Jamil,Hassine, Bechir Ben
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p. 735 - 743
(2013/01/15)
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- Kinetic resolution of (R,S)-pyrazolides containing substituents in the leaving pyrazole for increased lipase enantioselectivity
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With hydrolysis of (R,S)-azolides in water-saturated methyl tert-butyl ether (MTBE) via Candida antarctica lipase B (CALB) as the model system, (R,S)-pyrazolides containing a leaving 3-, 4- or 3,4-substituted-pyrazole moiety are selected as the best substrates for preparing various optically pure carboxylic acids containing an α-chiral center. Great improvements of enzyme activity for the (R)-enantiomers with excellent enantioselectivity (VR/VS > 100) are obtainable, if (R,S)-pyrazolides containing a leaving 3- or 3,4-substituted-pyrazole moiety are employed for the hydrolysis or alcoholysis by methanol in anhydrous MTBE. A detailed kinetic analysis for (R,S)-N-2-phenylpropionylpyrazoles indicates that a bulky 3-substituent such as 3-(3-bromophenyl) or 3-(2-pyridyl) in the leaving pyrazole moiety has profound effects on decreasing the nucleophilic attack and proton transfer of catalytic serine for the slow-reacting enantiomer in anhydrous MTBE, as well as that and substrate affinity for both enantiomers in water-saturated MTBE. The resolution platform is also successfully applied to the hydrolysis of (R,S)-pyrazolides in water-saturated cyclohexane via Candida rugosa lipase (Lipase MY) having opposite enantioselectivity to CALB.
- Wang, Pei-Yun,Wu, Chia-Hui,Ciou, Jyun-Fen,Wu, An-Chi,Tsai, Shau-Wei
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experimental part
p. 113 - 119
(2011/02/21)
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- A variant of Yarrowia lipolytica lipase with improved activity and enantioselectivity for resolution of 2-bromo-arylacetic acid esters
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A variant of Lip2p lipase from Yarrowia lipolytica yeast was used for the resolution of 2-bromophenyl and o-tolyl acid esters, an important class of chemical intermediates for the pharmaceutical industry. In comparison with wild-type Lip2p, this variant, which contains one single amino acid change in the active site of the enzyme, V232A, displayed an enantioselectivity enhanced by one order of magnitude for the resolution of 2-bromo-phenylacetic acid ethyl ester (E-value increased from 5.5 to 59 for wild-type and V232A, respectively) and by fourfold for the resolution of 2-bromo-o-tolylacetic acid ethyl ester (going from an E-value of 27 to 111 for the wild-type and V232A, respectively). A remarkable increase in reaction velocity was also observed for both compounds, as a result of a significant gain in reactivity towards the favoured (S)-enantiomer (3- and 16-fold increase for 2-bromo-phenylacetic and -o-tolylacetic acid ethyl esters, respectively). These results demonstrate the key role of the V232 amino acid in enantiomer recognition and selectivity.
- Cancino, Miguel,Bauchart, Philippe,Sandoval, Georgina,Nicaud, Jean-Marc,Andre, Isabelle,Dossat, Valerie,Marty, Alain
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p. 1608 - 1612
(2008/12/21)
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- Synthesis, characterization, and application of chiral ionic liquids and their polymers in micellar electrokinetic chromatography
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Two amino acid-derived (leucinol and N-methylpyrrolidinol) chiral ionic liquids are synthesized and characterized in both monomeric and polymeric forms. Leucinol-based chiral cationic surfactant is a room-temperature ionic liquid, and pyrrolidinol-based chiral cationic surfactant melts at 30-35 °C to form an ionic liquid (IL). The monomeric and polymeric ILs are thoroughly characterized to determine critical micelle concentration, aggregation number, polarity, optical rotation, and partial specific volume. Herein, we present the first enantioseparation using chiral IL as a pseudostationary phase in capillary electrophoresis. Chiral separation of two acidic analytes, (±)-α- bromophenylacetic acid and (±)-2-(2-chlorophenoxy)propanoic acid (±)-(2-PPA) can be achieved with both monomers and polymers of undecenoxycarbonyl-L-pryrrolidinol bromide (L-UCPB) and undecenoxycarbonyl-L- leucinol bromide (L-UCLB) at 25 mM surfactant concentration using phosphate buffer at pH 7.50. The chiral recognition seems to be facilitated by the extent of interaction of the acidic analytes with the cationic head-group of chiral selectors. Polysodium N-undecenoxycarbonyl-L-leucine sulfate (poly-L-SUCLS) and polysodium N-undecenoxycarbonyl-L-leucinate (poly-L-SUCL) were compared at high and low pH for the enantioseparation of (±)-(2-PPA). AtpH 7.5, poly-L-SUCLS, poly-L-SUCL, and (±)-(2-PPA) are negatively charged resulting in no enantioseparation. However, chiral separation was observed for (±)-(2-PPA) using poly-L-SUCLS at low pH (pH 2.00) at which the analyte is neutral. The comparison of chiral separation of anionic and cationic surfactants demonstrates that the electrostatic interaction between the acidic analyte and cationic micelle plays a profound role in enantioseparation.
- Rizvi, Syed Asad Ali,Shamsi, Shahab A.
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p. 7061 - 7069
(2008/02/12)
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- Triphenylphosphine-2,4,4,6-tetrabromo-2,5-cyclohexadienone complex as a reagent for preparation of carboxylic acid bromides
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Triphenylphosphine-2,4,4,6-tetrabromo-2,5-cyclohexadienone complex was successfully used as a new reagent for the synthesis of carboxylic acid bromides which were isolated as individual substances or were identified by conversion into the corresponding anilides. The reaction is chemoselective, and it can be applied to polyfunctional compounds, e.g., hydroxy acids.
- Matveeva,Podrugina,Sandakova,Zefirov
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p. 1469 - 1472
(2007/10/03)
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- Enantioselective protonation of silyl enol ethers and ketene disilyl acetals with Lewis acid-assisted chiral Bronsted acids: Reaction scope and mechanistic insights
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Enantioselective protonation is a potent and efficient way to construct chiral carbons. Here we report details of the reaction using Lewis acid-assisted chiral Bronsted acids (chiral LBAs). The 1:1 coordinate complex of tin tetrachloride and optically active binaphthol ((R)- or (S)-BINOL) can directly protonate various silyl enol ethers and ketene disilyl acetals to give the corresponding α-aryl ketones and α-arylcarboxylic acids, respectively, with high enantiomeric excesses (up to 98% ee). A catalytic version of enantioselective protonation has also been achieved using stoichiometric amounts of 2,6-dimethylphenol and catalytic amounts of monomethyl ether of optically active BINOL in the presence of tin tetrachloride. This protonation is also effective for producing α-halocarbonyl compounds (up to 91% ee). DFT calculations on the B3LYP/LANL2DZ level show that the conformational structure of the chiral LBA and the orientation of activated proton on (R)-BINOLs are important for understanding the absolute stereochemistry of the products.
- Nakamura, Shingo,Kaneeda, Masanobu,Ishihara, Kazuaki,Yamamoto, Hisashi
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p. 8120 - 8130
(2007/10/03)
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- Dynamic kinetic resolution in the hydrolysis of an α-bromo ester
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Bromide can be employed to racemise an α-bromo ester more rapidly than the corresponding acid (carboxylate), and this rate difference has been employed as the basis of a dynamic kinetic resolution reaction.
- Jones, Matthew M.,Williams, Jonathan M. J.
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p. 2519 - 2520
(2007/10/03)
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- Opioid Agonists an Antagonists. Peptides Containing N-Terminal Allyl Groups and/or a Thiomethylene Linkage in Place of a Peptide Bond
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Peptides containing N-allyl or N,N-diallyl groups at the N-terminus have been synthesized as potential opioid antagonists.A number of analogues with an amine bond replaced by a thiomethylene group have also been prepared.In brain binding assays and in gui
- Balboni, Gianfranco,Salvadori, Severo,Marastoni, Mauro,Tomatis, Roberto,Borea, Pier A.,Bianchi, Clementina
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p. 1645 - 1652
(2007/10/02)
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