The Experts below are selected from a list of 39 Experts worldwide ranked by ideXlab platform
Yves Langlois - One of the best experts on this subject based on the ideXlab platform.
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A Stereoselective Formal Synthesis of ()-Fumagillol
European Journal of Organic Chemistry, 2004Co-Authors: Olivier Bedel, Arnaud Haudrechy, Yves LangloisAbstract:A novel formal synthesis of fumagillol, a direct precursor of the antiangiogenic sesquiterpene fumagillin, is described. The main features of the synthesis are a stereoselective Claisen−Ireland Rearrangement, a ring-closing metathesis, a chemo- and stereoselective dihydroxylation, and a Julia−Kocienski olefination. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
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Claisen-Ireland Rearrangement: a new route to C-glycosides
Tetrahedron Letters, 1999Co-Authors: Thierry Vidal, Arnaud Haudrechy, Yves LangloisAbstract:A Claisen-Ireland Rearrangement led to the formation of C-glycan derivatives. Azidonitration-reduction or dihydroxylation afforded gluco- and galacto-derived β-C-glycosides. Subsequent deprotonation of bicyclic lactones 16 allowed the control of the newly created asymmetric centre.
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A Novel Stereoselective Route to a Fumagillin and Ovalicin Synthetic Intermediate
Tetrahedron Letters, 1999Co-Authors: Willy Picoul, Arnaud Haudrechy, Raquel Urchegui, Yves LangloisAbstract:Abstract A strategy using a highly stereoselective Claisen-Ireland Rearrangement followed by a Grubbs metathesis afforded in a good overall yield after further functionalisation a potentially synthetic precursor of fumagillin and ovalicin.
Arnaud Haudrechy - One of the best experts on this subject based on the ideXlab platform.
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Highly enantioselective sequential Claisen–Ireland/metathesis: synthesis of cycloalkenes bearing two contiguous highly functionalized asymmetric centres
Tetrahedron: Asymmetry, 2005Co-Authors: Antoine Français, Olivier Bedel, Willy Picoul, Abdelkrim Meddour, Jacques Courtieu, Arnaud HaudrechyAbstract:Abstract A sequence of two reactions, consisting of a highly stereoselective silylated ketene acetal Claisen–Ireland Rearrangement followed by a ring closing metathesis, gave a stereocontrolled access to various carbocycles.
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A Stereoselective Formal Synthesis of ()-Fumagillol
European Journal of Organic Chemistry, 2004Co-Authors: Olivier Bedel, Arnaud Haudrechy, Yves LangloisAbstract:A novel formal synthesis of fumagillol, a direct precursor of the antiangiogenic sesquiterpene fumagillin, is described. The main features of the synthesis are a stereoselective Claisen−Ireland Rearrangement, a ring-closing metathesis, a chemo- and stereoselective dihydroxylation, and a Julia−Kocienski olefination. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
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Claisen-Ireland Rearrangement: a new route to C-glycosides
Tetrahedron Letters, 1999Co-Authors: Thierry Vidal, Arnaud Haudrechy, Yves LangloisAbstract:A Claisen-Ireland Rearrangement led to the formation of C-glycan derivatives. Azidonitration-reduction or dihydroxylation afforded gluco- and galacto-derived β-C-glycosides. Subsequent deprotonation of bicyclic lactones 16 allowed the control of the newly created asymmetric centre.
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A Novel Stereoselective Route to a Fumagillin and Ovalicin Synthetic Intermediate
Tetrahedron Letters, 1999Co-Authors: Willy Picoul, Arnaud Haudrechy, Raquel Urchegui, Yves LangloisAbstract:Abstract A strategy using a highly stereoselective Claisen-Ireland Rearrangement followed by a Grubbs metathesis afforded in a good overall yield after further functionalisation a potentially synthetic precursor of fumagillin and ovalicin.
Guido Koch - One of the best experts on this subject based on the ideXlab platform.
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β-Aryl-Succinic Acid Hydroxamates as Dual Inhibitors of Matrix Metalloproteinases and Tumor Necrosis Factor Alpha Converting Enzyme
Journal of medicinal chemistry, 2002Co-Authors: Georg Kottirsch, Guido Koch, Roland Feifel, Ulf NeumannAbstract:Novel hydroxamate inhibitors of tumor necrosis factor converting enzyme (TACE) and matrix metalloproteases (MMPs) have been synthesized via the Claisen−Ireland Rearrangement. Aryl residues have been introduced to fill the enzyme's P1‘ specificity pocket. The best compound inhibits MMPs and TACE with nanomolar potency and inhibits the release of TNFα from cells with an IC50 of 48 nM. Oral administration to rats inhibits the LPS-induced plasma TNFα levels with an ED50 of 1 mg/kg.
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Highly diastereoselective Lewis acid promoted Claisen–Ireland Rearrangement
Tetrahedron Letters, 2002Co-Authors: Guido Koch, Philipp Janser, Georg Kottirsch, Eva Romero-gironAbstract:Abstract In the presence of catalytic amounts of Lewis acids silyl ketene acetals of trans allylic esters undergo a highly diastereoselective Claisen–Ireland Rearrangement to the corresponding disubstituted γ-δ-unsaturated erythro carboxylic acids. Diastereoselectivities of up to 15:1 were achieved when using TiCl 4 as catalyst. The uncatalyzed process proceeds slowly and with significantly lower selectivity. A wide range of aryl- and alkyl-substituents are tolerated.
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Process Development of a Dual MMP/TNF Inhibitor (SDZ 242-484)
Organic Process Research & Development, 2002Co-Authors: Guido Koch, Georg Kottirsch, Wietfeld Bernhard, Ernst KüstersAbstract:The compound (2R,3S)-N-4-((S)-2,2-Dimethyl-1-methylcarbamoyl-propyl)-N-1-hydroxy-2-hydroxymethyl-3-(4-methoxy-phenyl)succinamide (1; SDZ 242-484) shows antiinflammatory effects due to inhibition of matrix metalloproteases (MMP) and tumor necrosis factor-α activity (TNF). We describe the development of a chromatography-free process for a multikilogram-scale pilot-plant production. Two of the three chiral centers are introduced in a diastereoselective Claisen−Ireland Rearrangement. It was found that the selectivity of this step was significantly enhanced by the addition of catalytic amounts of Lewis acids. The resulting enantiomeric carboxylic acids were resolved with (S)-(−)-phenylethylamine. The use of osmiumtetroxide was considered to be problematic for pilot-plant use. Therefore, it was necessary to find an alternative method for the oxidative cleavage of the terminal olefin functionality. For the last chemical transformation, a hydrogenolytic cleavage of a benzyl group in the presence of a hydroxamate,...
Satoshi Yokoshima - One of the best experts on this subject based on the ideXlab platform.
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Total Synthesis of Lycoposerramine-R
Synlett, 2018Co-Authors: Shinya Watanabe, Masatsugu Ishikawa, Toshimune Nomura, Tohru Fukuyama, Satoshi YokoshimaAbstract:A total synthesis of lycoposerramine-R was accomplished. The synthesis featured a Claisen–Ireland Rearrangement to install a two-carbon unit, and a hetero-Diels–Alder reaction to form a cyclic enol ether that reacted with an ethynyl group to construct a cis-hydrindane core containing a quaternary carbon. A 2-pyridone synthesis using 2-(phenylsulfinyl)acetamide was used to complete the synthesis.
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Synthesis of the [7-5-5] tricyclic core of Daphniphyllum alkaloids
Organic & biomolecular chemistry, 2018Co-Authors: Yusuke Kitabayashi, Tohru Fukuyama, Satoshi YokoshimaAbstract:The [7-5-5] tricyclic core of the Daphniphyllum alkaloids was constructed, featuring a Claisen-Ireland Rearrangement to install the two contiguous stereogenic centers, E1cB elimination to form the tetrasubstituted C–C double bond, and a 2,3-Wittig Rearrangement to construct the quaternary carbon. Ring-closing metathesis and an intramolecular carbonyl ene reaction were employed for construction of the requisite ring system.
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A Unified Strategy for Kainoid Synthesis
European Journal of Organic Chemistry, 2014Co-Authors: Masaya Fujii, Satoshi Yokoshima, Tohru FukuyamaAbstract:A unified strategy for kainoid synthesis was developed. The key features of the strategy involve a Claisen–Ireland Rearrangement to construct the contiguous stereogenic centers and a palladium-catalyzed formation of the pyrrolidine ring with complete stereoselectivity. The present protocol has enabled rapid access to a wide range of kainoids with diverse types of substituents (alkenyl, aryl, and alkyl groups) at the 4-position of the pyrrolidine ring, starting from the common intermediate and appropriate acetic acid derivatives. To test the generality of the strategy, we have accomplished the syntheses of kainic acid, o-methoxyphenyl derivative (MFPA), and a novel cyclopropyl derivative (CPKA), using 3-methylbut-3-enoic acid, 2-(2-methoxyphenyl)acetic acid, and 2-cyclopropylacetic acid, respectively.
Georg Kottirsch - One of the best experts on this subject based on the ideXlab platform.
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β-Aryl-Succinic Acid Hydroxamates as Dual Inhibitors of Matrix Metalloproteinases and Tumor Necrosis Factor Alpha Converting Enzyme
Journal of medicinal chemistry, 2002Co-Authors: Georg Kottirsch, Guido Koch, Roland Feifel, Ulf NeumannAbstract:Novel hydroxamate inhibitors of tumor necrosis factor converting enzyme (TACE) and matrix metalloproteases (MMPs) have been synthesized via the Claisen−Ireland Rearrangement. Aryl residues have been introduced to fill the enzyme's P1‘ specificity pocket. The best compound inhibits MMPs and TACE with nanomolar potency and inhibits the release of TNFα from cells with an IC50 of 48 nM. Oral administration to rats inhibits the LPS-induced plasma TNFα levels with an ED50 of 1 mg/kg.
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Highly diastereoselective Lewis acid promoted Claisen–Ireland Rearrangement
Tetrahedron Letters, 2002Co-Authors: Guido Koch, Philipp Janser, Georg Kottirsch, Eva Romero-gironAbstract:Abstract In the presence of catalytic amounts of Lewis acids silyl ketene acetals of trans allylic esters undergo a highly diastereoselective Claisen–Ireland Rearrangement to the corresponding disubstituted γ-δ-unsaturated erythro carboxylic acids. Diastereoselectivities of up to 15:1 were achieved when using TiCl 4 as catalyst. The uncatalyzed process proceeds slowly and with significantly lower selectivity. A wide range of aryl- and alkyl-substituents are tolerated.
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Process Development of a Dual MMP/TNF Inhibitor (SDZ 242-484)
Organic Process Research & Development, 2002Co-Authors: Guido Koch, Georg Kottirsch, Wietfeld Bernhard, Ernst KüstersAbstract:The compound (2R,3S)-N-4-((S)-2,2-Dimethyl-1-methylcarbamoyl-propyl)-N-1-hydroxy-2-hydroxymethyl-3-(4-methoxy-phenyl)succinamide (1; SDZ 242-484) shows antiinflammatory effects due to inhibition of matrix metalloproteases (MMP) and tumor necrosis factor-α activity (TNF). We describe the development of a chromatography-free process for a multikilogram-scale pilot-plant production. Two of the three chiral centers are introduced in a diastereoselective Claisen−Ireland Rearrangement. It was found that the selectivity of this step was significantly enhanced by the addition of catalytic amounts of Lewis acids. The resulting enantiomeric carboxylic acids were resolved with (S)-(−)-phenylethylamine. The use of osmiumtetroxide was considered to be problematic for pilot-plant use. Therefore, it was necessary to find an alternative method for the oxidative cleavage of the terminal olefin functionality. For the last chemical transformation, a hydrogenolytic cleavage of a benzyl group in the presence of a hydroxamate,...