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Yoshiji Takemoto - One of the best experts on this subject based on the ideXlab platform.
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mechanistic insight into asymmetric hetero michael addition of α β unsaturated carboxylic acids catalyzed by multifunctional Thioureas
Journal of the American Chemical Society, 2018Co-Authors: Noboru Hayama, Ryuta Kuramoto, Tamas Foldes, Kazuya Nishibayashi, Yusuke Kobayashi, Imre Papai, Yoshiji TakemotoAbstract:Carboxylic acids and their corresponding carboxylate anions are generally utilized as Bronsted acids/bases and oxygen nucleophiles in organic synthesis. However, a few asymmetric reactions have used carboxylic acids as electrophiles. Although chiral Thioureas bearing both arylboronic acid and tertiary amine were found to promote the aza-Michael addition of BnONH2 to α,β-unsaturated carboxylic acids with moderate to good enantioselectivities, the reaction mechanism remains to be clarified. Detailed investigation of the reaction using spectroscopic analysis and kinetic studies identified tetrahedral borate complexes, comprising two carboxylate anions, as reaction intermediates. We realized a dramatic improvement in product enantioselectivity with the addition of 1 equiv of benzoic acid. In this aza-Michael reaction, the boronic acid not only activates the carboxylate ligand as a Lewis acid, together with the thiourea NH-protons, but also functions as a Bronsted base through a benzoyloxy anion to activate th...
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Mechanistic Insight into Asymmetric Hetero-Michael Addition of α,β-Unsaturated Carboxylic Acids Catalyzed by Multifunctional Thioureas
2018Co-Authors: Noboru Hayama, Ryuta Kuramoto, Kazuya Nishibayashi, Yusuke Kobayashi, Tamás Földes, Imre Pápai, Yoshiji TakemotoAbstract:Carboxylic acids and their corresponding carboxylate anions are generally utilized as Brønsted acids/bases and oxygen nucleophiles in organic synthesis. However, a few asymmetric reactions have used carboxylic acids as electrophiles. Although chiral Thioureas bearing both arylboronic acid and tertiary amine were found to promote the aza-Michael addition of BnONH2 to α,β-unsaturated carboxylic acids with moderate to good enantioselectivities, the reaction mechanism remains to be clarified. Detailed investigation of the reaction using spectroscopic analysis and kinetic studies identified tetrahedral borate complexes, comprising two carboxylate anions, as reaction intermediates. We realized a dramatic improvement in product enantioselectivity with the addition of 1 equiv of benzoic acid. In this aza-Michael reaction, the boronic acid not only activates the carboxylate ligand as a Lewis acid, together with the thiourea NH-protons, but also functions as a Brønsted base through a benzoyloxy anion to activate the nucleophile. Moreover, molecular sieves were found to play an important role in generating the ternary borate complexes, which were crucial for obtaining high enantioselectivity as demonstrated by DFT calculations. We also designed a new thiourea catalyst for the intramolecular oxa-Michael addition to suppress another catalytic pathway via a binary borate complex using steric hindrance between the catalyst and substrate. Finally, to demonstrate the synthetic versatility of both hetero-Michael additions, we used them to accomplish the asymmetric synthesis of key intermediates in pharmaceutically important molecules, including sitagliptin and α-tocopherol
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bifunctional hydrogen bond donors that bear a quinazoline or benzothiadiazine skeleton for asymmetric organocatalysis
Chemistry: A European Journal, 2011Co-Authors: Tsubasa Inokuma, Masaya Furukawa, Yusuke Suzuki, Kohzo Yoshida, Yoshiaki Yano, Katsumi Matsuzaki, Yoshiji TakemotoAbstract:Hydrogen-bond (HB)-donor catalysts that bear a 2-aminoquinazolin-4-(1H)-one or a 3-aminobenzothiadiazine-1,1-dioxide skeleton have been developed, and it has been shown that these catalyst motifs act similarly to other HB-donor catalysts such as Thioureas. The highly enantioselective hydrazination of 1,3-dicarbonyl compounds was realized even at room temperature with up to 96 % ee for 2-aminoquinazolin-4-(1H)-one-type catalysts, which were more effective than the corresponding urea and thiourea catalysts. In addition, benzothiadiazine-1,1-dioxide-type catalysts were shown to promote the isomerization of alkynoates to allenoates with high enantioselectivity. To overcome the problem that the products were obtained as mixtures with the starting alkynoates, we developed the tandem isomerization and cycloaddition of alkynoates for the synthesis of advanced chiral compounds such as bicyclo[2.2.1]heptenes and 3-alkylidene pyrrolidine without a significant loss of enantioselectivity.
Gilles Guichard - One of the best experts on this subject based on the ideXlab platform.
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isosteric substitutions of urea to thiourea and selenourea in aliphatic oligourea foldamers site specific perturbation of the helix geometry
Chemistry: A European Journal, 2015Co-Authors: Yella Reddy Nelli, Stéphanie Antunes, Arnaud Salaün, Emmanuelle Thinon, Stéphane Massip, Brice Kauffmann, Céline Douat, Gilles GuichardAbstract:: Nearly isosteric oxo to thioxo substitution was employed to interrogate the structure of foldamers with a urea backbone and explore the relationship between helical folding and hydrogen-bonding interactions. A series of oligomers with urea bonds substituted by thiourea bonds at discrete or all positions in the sequence have been prepared and their folding propensity was studied by using a combination of spectroscopic methods and X-ray diffraction. The outcome of oxo to thioxo replacements on the helical folding was found to depend on whether central or terminal ureas were modified. The canonical helix geometry was not affected upon insertion of Thioureas close to the negative end of the helix dipole, whereas Thioureas close to the positive pole were found to increase the terminal flexibility and cause helix fraying. Perturbation was amplified when a selenourea was incorporated instead, leading to a structure that is only partly folded.
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Isosteric Substitutions of Urea to Thiourea and Selenourea in Aliphatic Oligourea Foldamers: Site‐Specific Perturbation of the Helix Geometry
Chemistry: A European Journal, 2014Co-Authors: Yella Reddy Nelli, Stéphanie Antunes, Arnaud Salaün, Emmanuelle Thinon, Stéphane Massip, Brice Kauffmann, Céline Douat, Gilles GuichardAbstract:: Nearly isosteric oxo to thioxo substitution was employed to interrogate the structure of foldamers with a urea backbone and explore the relationship between helical folding and hydrogen-bonding interactions. A series of oligomers with urea bonds substituted by thiourea bonds at discrete or all positions in the sequence have been prepared and their folding propensity was studied by using a combination of spectroscopic methods and X-ray diffraction. The outcome of oxo to thioxo replacements on the helical folding was found to depend on whether central or terminal ureas were modified. The canonical helix geometry was not affected upon insertion of Thioureas close to the negative end of the helix dipole, whereas Thioureas close to the positive pole were found to increase the terminal flexibility and cause helix fraying. Perturbation was amplified when a selenourea was incorporated instead, leading to a structure that is only partly folded.
Ulrich Flörke - One of the best experts on this subject based on the ideXlab platform.
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long chain 1 acyl 3 arylThioureas as jack bean urease inhibitors synthesis kinetic mechanism and molecular docking studies
Journal of The Taiwan Institute of Chemical Engineers, 2017Co-Authors: Aamer Saeed, Sajidur Rehman, Pervaiz Ali Channar, Fayaz Ali Larik, Qamar Abbas, Mubashir Hassan, Hussain Raza, Ulrich FlörkeAbstract:Abstract The current research work reports the synthesis of novel long chain acyl thiourea derivatives as inhibitors of jack bean ureas. The title compounds were synthesized by the conversion of long chain carboxylic acids into corresponding acid chlorides followed by reaction with potassium thiocyanate to obtain a key reactive intermediate isothiocyanate, the latter was treated with suitably substituted aromatic anilines to afford the title 1-(substituted)phenyl-3-tetradecanoylThioureas. All of the compounds showed higher urease inhibitory activity than the standard thiourea. The compound 5f exhibited excellent enzyme inhibitory activity with IC50 0.0391 ± 0.0028 µM while IC50 of thiourea is 18.195 ± 0.382 µM. The kinetic mechanism analyzed by Lineweaver–Burk plots showed that compound 5f is a non-competitive type inhibitor. Docking studies suggested that Asp494, Ala636, His593, Ala636, Lue494, Asp521 and Arg439 are the major interacting residues in the binding site of the protein and may have an instrumental role in the inhibition of enzyme's function. Synthesized acyl Thioureas 5a–5k showed good docking score (−8.2 to −6.9 Kcal/mol) and efficacy of lead molecules was investigated by carrying out pharmacokinetic studies, Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) assessment justified that these novel synthesized compounds showed good lead like potential with little hepatotoxic and skin sensitive effects. Chemo-informatics properties were evaluated by computational approaches and it was found that synthesized compounds mostly obeyed the Lipinski's rule.
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Recent developments in chemistry, coordination, structure and biological aspects of 1-(acyl/aroyl)-3-(substituted) Thioureas
Research on Chemical Intermediates, 2017Co-Authors: Aamer Saeed, Rabia Qamar, Tanzeela Abdul Fattah, Ulrich Flörke, Mauricio F. ErbenAbstract:1-(Acyl / aroyl)-3-(substituted)Thioureas are privileged architectures that have received remarkable attention of researchers in view of their variable topological aspects, binding modes and broad spectrum promising pharmacological properties. Reactivity of acyl thiourea derivatives has presented various organic transformations into other demanding scaffolds and this is an attractive strategy for synthetic chemists to access heterocyclic cores. Multiple binding sites make them flexible ligands for complexation with transition metals thus occupying a distinct position in coordination chemistry. 1-(Acyl / aroyl)-3-(substituted)Thioureas have also emerged as attractive candidates in various fields such as ion sensors, corrosion inhibitors, molecular electronics, in metal extraction and in pharmaceuticals. The medicinal chemistry of this organo-sulfur framework and the derived metal complexes has witnessed fantastic progress in the current era. In continuation of our efforts to compile data on the structural aspects and numerous applications of 1-(acyl / aroyl)-3-(substituted)thiourea analogs, continuous advances have prompted us to present an overview of the last 2 years literature on this exciting family of compounds through this review article.
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a review on the chemistry coordination structure and biological properties of 1 acyl aroyl 3 substituted Thioureas
Journal of Sulfur Chemistry, 2014Co-Authors: Aamer Saeed, Ulrich Flörke, Mauricio F. ErbenAbstract:This review provides an overview of the chemistry, structure and potential applications of 1-(acyl/aroyl)-3-(mono-substituted) and 1-(acyl/aroyl)-3,3-(di-substituted) Thioureas, with general formula R1C(O)N(1)HC(S)N(3)R2R3. In recent years, the title compounds have found extensive applications as ligands in coordination chemistry. The effect that nitrogen substituents exert on the intra- and intermolecular hydrogen-bonding interactions is discussed, including their role on the coordination properties displayed by these ligands. Novel applications of transition metal complexes bearing 1-(acyl/aroyl)-3-(mono- and di-substituted) Thioureas are introduced. Biological aspects are also highlighted. As recently demonstrated, high-throughput screening assay and structure–activity analyses are feasible for this class of compounds. The chemical versatility of 1-(acyl)-3-(substituted) thiourea molecules and the derived metal complexes, together with the possibility of determining detailed structural properties, join...
Aamer Saeed - One of the best experts on this subject based on the ideXlab platform.
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long chain 1 acyl 3 arylThioureas as jack bean urease inhibitors synthesis kinetic mechanism and molecular docking studies
Journal of The Taiwan Institute of Chemical Engineers, 2017Co-Authors: Aamer Saeed, Sajidur Rehman, Pervaiz Ali Channar, Fayaz Ali Larik, Qamar Abbas, Mubashir Hassan, Hussain Raza, Ulrich FlörkeAbstract:Abstract The current research work reports the synthesis of novel long chain acyl thiourea derivatives as inhibitors of jack bean ureas. The title compounds were synthesized by the conversion of long chain carboxylic acids into corresponding acid chlorides followed by reaction with potassium thiocyanate to obtain a key reactive intermediate isothiocyanate, the latter was treated with suitably substituted aromatic anilines to afford the title 1-(substituted)phenyl-3-tetradecanoylThioureas. All of the compounds showed higher urease inhibitory activity than the standard thiourea. The compound 5f exhibited excellent enzyme inhibitory activity with IC50 0.0391 ± 0.0028 µM while IC50 of thiourea is 18.195 ± 0.382 µM. The kinetic mechanism analyzed by Lineweaver–Burk plots showed that compound 5f is a non-competitive type inhibitor. Docking studies suggested that Asp494, Ala636, His593, Ala636, Lue494, Asp521 and Arg439 are the major interacting residues in the binding site of the protein and may have an instrumental role in the inhibition of enzyme's function. Synthesized acyl Thioureas 5a–5k showed good docking score (−8.2 to −6.9 Kcal/mol) and efficacy of lead molecules was investigated by carrying out pharmacokinetic studies, Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) assessment justified that these novel synthesized compounds showed good lead like potential with little hepatotoxic and skin sensitive effects. Chemo-informatics properties were evaluated by computational approaches and it was found that synthesized compounds mostly obeyed the Lipinski's rule.
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Recent developments in chemistry, coordination, structure and biological aspects of 1-(acyl/aroyl)-3-(substituted) Thioureas
Research on Chemical Intermediates, 2017Co-Authors: Aamer Saeed, Rabia Qamar, Tanzeela Abdul Fattah, Ulrich Flörke, Mauricio F. ErbenAbstract:1-(Acyl / aroyl)-3-(substituted)Thioureas are privileged architectures that have received remarkable attention of researchers in view of their variable topological aspects, binding modes and broad spectrum promising pharmacological properties. Reactivity of acyl thiourea derivatives has presented various organic transformations into other demanding scaffolds and this is an attractive strategy for synthetic chemists to access heterocyclic cores. Multiple binding sites make them flexible ligands for complexation with transition metals thus occupying a distinct position in coordination chemistry. 1-(Acyl / aroyl)-3-(substituted)Thioureas have also emerged as attractive candidates in various fields such as ion sensors, corrosion inhibitors, molecular electronics, in metal extraction and in pharmaceuticals. The medicinal chemistry of this organo-sulfur framework and the derived metal complexes has witnessed fantastic progress in the current era. In continuation of our efforts to compile data on the structural aspects and numerous applications of 1-(acyl / aroyl)-3-(substituted)thiourea analogs, continuous advances have prompted us to present an overview of the last 2 years literature on this exciting family of compounds through this review article.
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a review on the chemistry coordination structure and biological properties of 1 acyl aroyl 3 substituted Thioureas
Journal of Sulfur Chemistry, 2014Co-Authors: Aamer Saeed, Ulrich Flörke, Mauricio F. ErbenAbstract:This review provides an overview of the chemistry, structure and potential applications of 1-(acyl/aroyl)-3-(mono-substituted) and 1-(acyl/aroyl)-3,3-(di-substituted) Thioureas, with general formula R1C(O)N(1)HC(S)N(3)R2R3. In recent years, the title compounds have found extensive applications as ligands in coordination chemistry. The effect that nitrogen substituents exert on the intra- and intermolecular hydrogen-bonding interactions is discussed, including their role on the coordination properties displayed by these ligands. Novel applications of transition metal complexes bearing 1-(acyl/aroyl)-3-(mono- and di-substituted) Thioureas are introduced. Biological aspects are also highlighted. As recently demonstrated, high-throughput screening assay and structure–activity analyses are feasible for this class of compounds. The chemical versatility of 1-(acyl)-3-(substituted) thiourea molecules and the derived metal complexes, together with the possibility of determining detailed structural properties, join...
Rafael Pedrosa - One of the best experts on this subject based on the ideXlab platform.
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Chiral Bifunctional Thioureas and Squaramides Grafted into Old Polymers of Intrinsic Microporosity for Novel Applications
MDPI AG, 2018Co-Authors: Maria Valle, Jose M Andres, Alicia Maestro, Laura Martín, Rafael PedrosaAbstract:We have prepared different polymeric chiral bifunctional Thioureas and squaramides by modification of the very well-known polymers of intrinsic microporosity (PIM), specifically PIM-1 and PIM-CO-1, to be used as recoverable organocatalysts. The installation of the chiral structures into the polymers has been done in two or three steps in high yields. The catalytic activity of the resulting materials has been proved in the stereoselective nitro-Michael addition and in a cascade process, which allows the synthesis of enantioenriched 4H-chromene derivatives. Squaramide II and thiourea III have been used in six cycles maintaining their activity
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supported bifunctional Thioureas as recoverable and reusable catalysts for enantioselective nitro michael reactions
Beilstein Journal of Organic Chemistry, 2016Co-Authors: Jose M Andres, Miriam Ceballos, Alicia Maestro, Isabel Sanz, Rafael PedrosaAbstract:The catalytic activity of different supported bifunctional Thioureas on sulfonylpolystyrene resins has been studied in the nitro-Michael addition of different nucleophiles to trans-β-nitrostyrene derivatives. The activity of the catalysts depends on the length of the tether linking the chiral thiourea to the polymer. The best results were obtained with the thiourea derived from (L)-valine and 1,6-hexanediamine. The catalysts can be used in only 2 mol % loading, and reused for at least four cycles in neat conditions. The ball milling promoted additions also worked very well.
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bottom up synthesis of supported Thioureas and their use in enantioselective solvent free aza henry and michael additions
ChemPlusChem, 2016Co-Authors: Jose M Andres, Noelia De La Cruz, Maria Valle, Rafael PedrosaAbstract:Two sets of supported chiral Thioureas, which differ in the length of the tether that connects the chiral appendage to the polymer structure and the effective functionalization, have been prepared by copolymerization of styrene, novel styryl Thioureas derived from l-valine, and divinylbenzene. The efficiency of these polymeric Thioureas has been tested in two different enantioselective transformations, namely, aza-Henry and nitro-Michael reactions, in neat reaction conditions. The obtained results show that it is possible to recycle the thiourea, and they are able to promote the reactions with good enantioselectivity at a low catalyst loading.
