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Andrew D. Smith - One of the best experts on this subject based on the ideXlab platform.
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Enantioselective Synthesis of β‑Fluoro-β-aryl-α-aminopentenamides by Organocatalytic [2,3]-Sigmatropic Rearrangement
2017Co-Authors: Kevin Kasten, Alexandra M. Z. Slawin, Andrew D. SmithAbstract:The Tetramisole-promoted catalytic enantioselective [2,3]-sigmatropic rearrangement of quaternary ammonium salts bearing a (Z)-3-fluoro-3-arylprop-2-ene group generates, after addition of benzylamine, a range of β-fluoro-β-aryl-α-aminopentenamides containing a stereogenic tertiary fluorine substituent. Cyclic and acyclic nitrogen substituents as well as various aromatic substituents are tolerated, giving the β-fluoro-β-aryl-α-aminopentenamide products in up to 76% yield, 96:4 dr, and 98:2 er
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Isothiourea-Catalyzed Enantioselective Addition of 4‑Nitrophenyl Esters to Iminium Ions
2017Co-Authors: Jude N. Arokianathar, Alexandra M. Z. Slawin, Aileen B. Frost, Darren Stead, Andrew D. SmithAbstract:Isothioureas catalyze the enantioselective addition of 4-nitrophenyl esters to tetrahydroisoquinoline-derived iminium ions. 4-Nitrophenoxide, generated in situ from initial N-acylation of the isothiourea by the 4-nitrophenyl ester, is used to facilitate catalyst turnover in this reaction process. Optimization showed that 4-nitrophenyl esters give the best reactivity in this protocol over a range of alternative aryl esters, with the observed enantioselectivity markedly dependent on the nature of the iminium counterion. Highest yields and enantioselectivity were obtained using iminium bromide ions generated in situ via photoredox catalysis using BrCCl3 and Ru(bpy)3Cl2 (0.5 mol %) and commercially available Tetramisole (5 mol %) as the Lewis base catalyst. The scope and limitations of this procedure was developed, giving the desired β-amino amide products in up to 96% yield, 79:21 diastereomeric ratio (dr), and ermajor (2R,1′S) 99.5:0.5
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stereodivergent organocatalytic intramolecular michael addition lactonization for the asymmetric synthesis of substituted dihydrobenzofurans and tetrahydrofurans
Chemistry: A European Journal, 2014Co-Authors: Dorine Belmessieri, Alix De La Houpliere, Ewen D D Calder, James E Taylor, Andrew D. SmithAbstract:A stereodivergent asymmetric Lewis base cata- lyzed Michael addition/lactonization of enone acids into sub- stituted dihydrobenzofuran and tetrahydrofuran derivatives is reported. Commercially available (S)-()-Tetramisole hydro- chloride gives products with high syn diastereoselectivity in excellent enantioselectivity (up to 99:1 d.r.syn/anti ,9 9 % ee syn), whereas using a cinchona alkaloid derived catalyst gives the corresponding anti-diastereoisomers as the major product (up to 10:90 d.r.syn/anti ,9 9 % ee anti).
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Telescoped Synthesis of Stereodefined Pyrrolidines
Organic letters, 2013Co-Authors: Dorine Belmessieri, Alexandra M. Z. Slawin, David B. Cordes, Andrew D. SmithAbstract:Telescoped and one-pot olefination/asymmetric functionalization approaches to disubstituted pyrrolidines (dr up to 99:1, up to 99% ee) have been developed using commercially available Tetramisole (0.1 to 5 mol %). Using OTMS-quinidine as the Lewis base gives preferential access to an anti-configured pyrrolidine in high enantioselectivity.
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organocatalytic functionalization of carboxylic acids isothiourea catalyzed asymmetric intra and intermolecular michael addition lactonizations
Journal of the American Chemical Society, 2011Co-Authors: Dorine Belmessieri, Carmen Simal, Louis C. Morrill, Alexandra M. Z. Slawin, Andrew D. SmithAbstract:Tetramisole promotes the catalytic asymmetric intramolecular Michael addition−lactonization of a variety of enone acids, giving carbo- and heterocyclic products with high diastereo- and enantiocontrol (up to 99:1 dr, up to 99% ee) that are readily derivatized to afford functionalized indene and dihydrobenzofuran carboxylates. Chiral isothioureas also promote the catalytic asymmetric intermolecular Michael addition−lactonization of arylacetic acids and α-keto-β,γ-unsaturated esters, giving anti-dihydropyranones with high diastereo- and enantiocontrol (up to 98:2 dr, up to 99% ee).
Dorine Belmessieri - One of the best experts on this subject based on the ideXlab platform.
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stereodivergent organocatalytic intramolecular michael addition lactonization for the asymmetric synthesis of substituted dihydrobenzofurans and tetrahydrofurans
Chemistry: A European Journal, 2014Co-Authors: Dorine Belmessieri, Alix De La Houpliere, Ewen D D Calder, James E Taylor, Andrew D. SmithAbstract:A stereodivergent asymmetric Lewis base cata- lyzed Michael addition/lactonization of enone acids into sub- stituted dihydrobenzofuran and tetrahydrofuran derivatives is reported. Commercially available (S)-()-Tetramisole hydro- chloride gives products with high syn diastereoselectivity in excellent enantioselectivity (up to 99:1 d.r.syn/anti ,9 9 % ee syn), whereas using a cinchona alkaloid derived catalyst gives the corresponding anti-diastereoisomers as the major product (up to 10:90 d.r.syn/anti ,9 9 % ee anti).
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Telescoped Synthesis of Stereodefined Pyrrolidines
Organic letters, 2013Co-Authors: Dorine Belmessieri, Alexandra M. Z. Slawin, David B. Cordes, Andrew D. SmithAbstract:Telescoped and one-pot olefination/asymmetric functionalization approaches to disubstituted pyrrolidines (dr up to 99:1, up to 99% ee) have been developed using commercially available Tetramisole (0.1 to 5 mol %). Using OTMS-quinidine as the Lewis base gives preferential access to an anti-configured pyrrolidine in high enantioselectivity.
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organocatalytic functionalization of carboxylic acids isothiourea catalyzed asymmetric intra and intermolecular michael addition lactonizations
Journal of the American Chemical Society, 2011Co-Authors: Dorine Belmessieri, Carmen Simal, Louis C. Morrill, Alexandra M. Z. Slawin, Andrew D. SmithAbstract:Tetramisole promotes the catalytic asymmetric intramolecular Michael addition−lactonization of a variety of enone acids, giving carbo- and heterocyclic products with high diastereo- and enantiocontrol (up to 99:1 dr, up to 99% ee) that are readily derivatized to afford functionalized indene and dihydrobenzofuran carboxylates. Chiral isothioureas also promote the catalytic asymmetric intermolecular Michael addition−lactonization of arylacetic acids and α-keto-β,γ-unsaturated esters, giving anti-dihydropyranones with high diastereo- and enantiocontrol (up to 98:2 dr, up to 99% ee).
Alexandra M. Z. Slawin - One of the best experts on this subject based on the ideXlab platform.
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Enantioselective Synthesis of β‑Fluoro-β-aryl-α-aminopentenamides by Organocatalytic [2,3]-Sigmatropic Rearrangement
2017Co-Authors: Kevin Kasten, Alexandra M. Z. Slawin, Andrew D. SmithAbstract:The Tetramisole-promoted catalytic enantioselective [2,3]-sigmatropic rearrangement of quaternary ammonium salts bearing a (Z)-3-fluoro-3-arylprop-2-ene group generates, after addition of benzylamine, a range of β-fluoro-β-aryl-α-aminopentenamides containing a stereogenic tertiary fluorine substituent. Cyclic and acyclic nitrogen substituents as well as various aromatic substituents are tolerated, giving the β-fluoro-β-aryl-α-aminopentenamide products in up to 76% yield, 96:4 dr, and 98:2 er
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Isothiourea-Catalyzed Enantioselective Addition of 4‑Nitrophenyl Esters to Iminium Ions
2017Co-Authors: Jude N. Arokianathar, Alexandra M. Z. Slawin, Aileen B. Frost, Darren Stead, Andrew D. SmithAbstract:Isothioureas catalyze the enantioselective addition of 4-nitrophenyl esters to tetrahydroisoquinoline-derived iminium ions. 4-Nitrophenoxide, generated in situ from initial N-acylation of the isothiourea by the 4-nitrophenyl ester, is used to facilitate catalyst turnover in this reaction process. Optimization showed that 4-nitrophenyl esters give the best reactivity in this protocol over a range of alternative aryl esters, with the observed enantioselectivity markedly dependent on the nature of the iminium counterion. Highest yields and enantioselectivity were obtained using iminium bromide ions generated in situ via photoredox catalysis using BrCCl3 and Ru(bpy)3Cl2 (0.5 mol %) and commercially available Tetramisole (5 mol %) as the Lewis base catalyst. The scope and limitations of this procedure was developed, giving the desired β-amino amide products in up to 96% yield, 79:21 diastereomeric ratio (dr), and ermajor (2R,1′S) 99.5:0.5
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Telescoped Synthesis of Stereodefined Pyrrolidines
Organic letters, 2013Co-Authors: Dorine Belmessieri, Alexandra M. Z. Slawin, David B. Cordes, Andrew D. SmithAbstract:Telescoped and one-pot olefination/asymmetric functionalization approaches to disubstituted pyrrolidines (dr up to 99:1, up to 99% ee) have been developed using commercially available Tetramisole (0.1 to 5 mol %). Using OTMS-quinidine as the Lewis base gives preferential access to an anti-configured pyrrolidine in high enantioselectivity.
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organocatalytic functionalization of carboxylic acids isothiourea catalyzed asymmetric intra and intermolecular michael addition lactonizations
Journal of the American Chemical Society, 2011Co-Authors: Dorine Belmessieri, Carmen Simal, Louis C. Morrill, Alexandra M. Z. Slawin, Andrew D. SmithAbstract:Tetramisole promotes the catalytic asymmetric intramolecular Michael addition−lactonization of a variety of enone acids, giving carbo- and heterocyclic products with high diastereo- and enantiocontrol (up to 99:1 dr, up to 99% ee) that are readily derivatized to afford functionalized indene and dihydrobenzofuran carboxylates. Chiral isothioureas also promote the catalytic asymmetric intermolecular Michael addition−lactonization of arylacetic acids and α-keto-β,γ-unsaturated esters, giving anti-dihydropyranones with high diastereo- and enantiocontrol (up to 98:2 dr, up to 99% ee).
Markus R Baumgartner - One of the best experts on this subject based on the ideXlab platform.
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cocaine adulteration with the anthelminthic Tetramisole levamisole dexamisole long term monitoring of its intake by chiral lc ms ms analysis of cocaine positive hair samples
Drug Testing and Analysis, 2019Co-Authors: Milena M Madry, Thomas Kraemer, Markus R BaumgartnerAbstract:Recent studies indicate that not only the anthelminthic levamisole but also the racemate Tetramisole (R-/S-phenyltetraimidazothiazole, PTHIT) was found as adulterant for cocaine. We herein report on the investigation of the prevalence of PTHIT among cocaine-positive hair samples and the discrimination of the presence of its stereoisomers levamisole and dexamisole. Cocaine-positive hair samples were collected in a forensic context in 2015 and mainly 2017 (n=724). Cocaine and PTHIT concentrations have been determined by achiral liquid chromatography-tandem mass spectrometry (LC-MS/MS). For distinction of levamisole/dexamisole chiral LC-MS/MS was performed. Cocaine hair concentrations ranged from 500 (cut-off) to approximately 800,000 pg/mg. The study demonstrates a strong prevalence of PTHIT in cocaine users' hair (87 %, n=627). PTHIT hair concentrations ranged from below LLOQ 3.5 to approximately 61,000 pg/mg (median: 260 pg/mg). Surprisingly, enantiomeric ratios of levamisole/dexamisole ranged from 0.17 to 1.34 (median: 0.63). Therefore, PTHIT-adulterated street cocaine samples (n=24) seized between 2013 and 2016 were tested. Samples mainly contained racemic Tetramisole (87.5 %), only one sample contained levamisole only and two samples contained non-racemic PTHIT. Our experiments suggest that the presence of Tetramisole in biological samples may have hitherto been underestimated. Most probably higher dexamisole than levamisole concentrations in hair specimens arise from stereoselective metabolism and/or elimination. This is particularly important in light of the different pharmacological activities of the two enantiomers and potentially different adverse effects. Toxicological interpretations in intoxication cases with adulterated cocaine should not only consider levamisole but also Tetramisole and terminology in scientific contributions should be used accordingly.
Kenya Nakata - One of the best experts on this subject based on the ideXlab platform.
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kinetic resolution of racemic secondary benzylic alcohols by the enantioselective esterification using pyridine 3 carboxylic anhydride 3 pca with chiral acyl transfer catalysts
Helvetica Chimica Acta, 2012Co-Authors: Isamu Shiina, Kenya Nakata, Keisuke Ono, Teruaki MukaiyamaAbstract:Pyridine-3-carboxylic anhydride (3-PCA) was found to function as an efficient coupling reagent for the preparation of carboxylic esters from various carboxylic acids with alcohols under mild conditions by a simple experimental procedure. This novel condensation reagent 3-PCA was applicable not only for the synthesis of achiral carboxylic esters catalyzed by 4-(dimethylamino)pyridine (DMAP) but also for the production of chiral carboxylic esters by the combination of chiral nucleophilic catalyst, such as Tetramisole (=2,3,5,6-tetrahydro-6-phenylimidazo[2,1-b][1,3]thiazole) derivatives. An efficient kinetic resolution of racemic benzylic alcohols with achiral carboxylic acids was achieved by using 3-PCA in the presence of (R)-benzoTetramisole ((R)-BTM), and a variety of optically active carboxylic esters were produced with high enantiomeric excesses by this new chiral induction system without using a tertiary amine.
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Kinetic Resolution of Racemic Carboxylic Acids Using Achiral Alcohols by the Promotion of Benzoic Anhydrides and Tetramisole Derivatives: Production of Chiral Nonsteroidal Anti-Inflammatory Drugs and Their Esters
European Journal of Organic Chemistry, 2008Co-Authors: Isamu Shiina, Kenya Nakata, Yu‐suke OndaAbstract:A variety of optically active carboxylic esters were produced by kinetic resolution of racemic carboxylic acids by using achiral alcohols, benzoic anhydrides, and Birman's Tetramisole-type catalysts. Bis(α-naphthyl)methanol is a very effective reagent for producing the corresponding esters with high ee values in the presence of 4-methoxybenzoic anhydride (PMBA) as the coupling reagent by promotion of benzoTetramisole derivatives (BTM, α-Np-BTM, and β-Np-BTM). This protocol directly provides chiral carboxylic esters from free carboxylic acids and achiral alcohols by utilizing a transacylation process to generate the mixed anhydrides from the acid components with benzoic anhydride derivatives in the presence of chiral catalysts.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
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the first asymmetric esterification of free carboxylic acids with racemic alcohols using benzoic anhydrides and Tetramisole derivatives an application to the kinetic resolution of secondary benzylic alcohols
Tetrahedron Letters, 2007Co-Authors: Isamu Shiina, Kenya NakataAbstract:Abstract A variety of optically active carboxylic esters are produced by the kinetic resolution of racemic secondary benzylic alcohols using free carboxylic acids with benzoic anhydride and Tetramisole derivatives. 4-Methoxybenzoic anhydride (PMBA) is the best reagent to use in producing the corresponding esters in high ee when the reaction is catalyzed by (+)-benzoTetramisole (BTM); by contrast, when non-substituted benzoic anhydride is used as a coupling reagent, the resulting optically active alcohols are obtained with high selectivities. This protocol directly produces chiral carboxylic esters from free carboxylic acids and racemic secondary alcohols by utilizing the trans-acylation process to generate mixed anhydrides from acid components and benzoic anhydride derivatives under the influence of chiral catalysts.