Search

Your search keyword '"Joannesse, Caroline"' showing total 24 results
Start Over Author "Joannesse, Caroline"
24 results on '"Joannesse, Caroline"'

1. Design of a potent and selective dual JAK1/TYK2 inhibitor

Author

Mammoliti, Oscar, Menet, Christel, Cottereaux, Céline, Blanc, Javier, De Blieck, Ann, Coti, Ghjuvanni, Geney, Raphaël, Oste, Line, Ostyn, Koen, Palisse, Adeline, Quinton, Evelyne, Schmitt, Benoit, Borgonovi, Monica, Parent, Isabelle, Jagerschmidt, Catherine, De Vos, Steve, Vayssiere, Béatrice, López-Ramos, Miriam, Shoji, Kenji, Brys, Reginald, Amantini, David, Galien, René, and Joannesse, Caroline

Published
2024
Full Text
View/download PDF

2. Isothiourea-promoted O- to C-carboxyl transfer reactions

Author

Joannesse, Caroline and Smith, Andrew D.

Subjects
660, Organocatalysis, Isothiourea, Asymmetric catalysis, Steglich rearrangement
Abstract

This thesis describes an extensive investigation of the O- to C-carboxyl transfer of oxazolyl carbonates using isothioureas as Lewis base catalysts. The structural requirements of simple bicyclic amidines and isothioureas to promote this transformation have been investigated, showing that the catalytic efficiency and product distribution of these reactions are markedly affected by the catalyst structure. The optimal isothiourea catalyst was efficiently applied to the rearrangement of a wide range of oxazolyl, benzofuranyl and indolyl carbonates. The structural motif of tetrahydropyrimidine-based isothioureas has then been evaluated in order to develop an asymmetric variant of the O- to C-carboxyl transfer of oxazolyl carbonates. A number of chiral isothioureas bearing stereodirecting groups in C(2) and/or C(3) have been synthesised and used in this rearrangement, showing that a C(2)-stereodirecting unit is essential for high enantioselectivity, with an additional C(3)-substituent increasing the reactivity. The optimal chiral C(2)-substituted isothioureas identified are general and efficient asymmetric catalysts for O- to C-carboxyl transfer of oxazolyl carbonates, generating a quaternary stereocentre with high enantioselectivity (up to 94% ee). The origin of the enantioselectivity of this process has been probed mechanistically and rationalised computationally. Having gained an insight into the structural motifs of isothioureas required to impart good catalytic activity and asymmetric induction in the O- to C-carboxyl transfer of oxazolyl carbonates, the mechanism of this reaction was probed using kinetic and mechanistic experiments. ¹⁹F NMR spectroscopic analysis allowed the evolution of product, by-product and intermediate throughout the reaction to be monitored while a number of crossover and stability experiments gave additional information about the catalytic cycle. Extension to a related system has been demonstrated with the O- to C-carboxyl transfer of furanyl carbonates, producing a mixture of α- and γ-butenolides depending on the nature of the Lewis base employed. DMAP gives a mixture of both regioisomers with a preference for the α-regioisomer, while NHCs lead predominantly to the γ-regioisomer. Chiral isothioureas have been used to promote this rearrangement, giving the major α-regioisomer with good enantioselectivity (up to 83% ee). To quantify the different reactivities observed with these isothioureas, their nucleophilicities and Lewis basicities using the stopped-flow technique have been determined. Finally, model studies toward the synthesis of the natural product calcaridine A, using the methodology developed herein, have been investigated.

Published
2011

3. Correction to “Discovery of GLPG2451, a Novel Once Daily Potentiator for the Treatment of Cystic Fibrosis”

Author

Van der Plas, Steven E., primary, Kelgtermans, Hans, additional, Mammoliti, Oscar, additional, Menet, Christel, additional, Tricarico, Giovanni, additional, De Blieck, Ann, additional, Joannesse, Caroline, additional, De Munck, Tom, additional, Lambin, Dominique, additional, Cowart, Marlon, additional, Dropsit, Sebastien, additional, Martina, Sebastien L. X., additional, Gees, Maarten, additional, Wesse, Anne-Sophie, additional, Conrath, Katja, additional, and Andrews, Martin, additional

Published
2021
Full Text
View/download PDF

4. Discovery of the S1P2 Antagonist GLPG2938 (1-[2-Ethoxy-6-(trifluoromethyl)-4-pyridyl]-3-[[5-methyl-6-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]pyridazin-3-yl]methyl]urea), a Preclinical Candidate for the Treatment of Idiopathic Pulmonary Fibrosis

Author

Mammoliti, Oscar, primary, Palisse, Adeline, additional, Joannesse, Caroline, additional, El Bkassiny, Sandy, additional, Allart, Brigitte, additional, Jaunet, Alex, additional, Menet, Christel, additional, Coornaert, Beatrice, additional, Sonck, Kathleen, additional, Duys, Inge, additional, Clément-Lacroix, Philippe, additional, Oste, Line, additional, Borgonovi, Monica, additional, Wakselman, Emanuelle, additional, Christophe, Thierry, additional, Houvenaghel, Nicolas, additional, Jans, Mia, additional, Heckmann, Bertrand, additional, Sanière, Laurent, additional, and Brys, Reginald, additional

Published
2021
Full Text
View/download PDF

5. Discovery of GLPG2451, a Novel Once Daily Potentiator for the Treatment of Cystic Fibrosis

Author

Van der Plas, Steven E., primary, Kelgtermans, Hans, additional, Mammoliti, Oscar, additional, Menet, Christel, additional, Tricarico, Giovanni, additional, De Blieck, Ann, additional, Joannesse, Caroline, additional, De Munck, Tom, additional, Lambin, Dominique, additional, Cowart, Marlon, additional, Dropsit, Sebastien, additional, Martina, Sebastien L. X., additional, Gees, Maarten, additional, Wesse, Anne-Sophie, additional, Conrath, Katja, additional, and Andrews, Martin, additional

Published
2021
Full Text
View/download PDF

6. Discovery of N-(3-Carbamoyl-5,5,7,7-tetramethyl-5,7-dihydro-4H-thieno[2,3-c]pyran-2-yl)-lH-pyrazole-5-carboxamide (GLPG1837), a Novel Potentiator Which Can Open Class III Mutant Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Channels to a High Extent

Author

Van der Plas, Steven E., primary, Kelgtermans, Hans, additional, De Munck, Tom, additional, Martina, Sébastien L. X., additional, Dropsit, Sébastien, additional, Quinton, Evelyne, additional, De Blieck, Ann, additional, Joannesse, Caroline, additional, Tomaskovic, Linda, additional, Jans, Mia, additional, Christophe, Thierry, additional, van der Aar, Ellen, additional, Borgonovi, Monica, additional, Nelles, Luc, additional, Gees, Maarten, additional, Stouten, Pieter, additional, Van Der Schueren, Jan, additional, Mammoliti, Oscar, additional, Conrath, Katja, additional, and Andrews, Martin, additional

Published
2018
Full Text
View/download PDF

7. Discovery of N-(3-Carbamoyl-5,5,7,7-tetramethyl-5,7-dihydro-4H-thieno[2,3-c]pyran-2-yl)-lH-pyrazole-5-carboxamide (GLPG1837), a Novel Potentiator Which Can Open Class III Mutant Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Channels to a High Extent

Author

Van der Plas, Steven E., Kelgtermans, Hans, De Munck, Tom, Martina, Sébastien L. X., Dropsit, Sébastien, Quinton, Evelyne, De Blieck, Ann, Joannesse, Caroline, Tomaskovic, Linda, Jans, Mia, Christophe, Thierry, van der Aar, Ellen, Borgonovi, Monica, Nelles, Luc, Gees, Maarten, Stouten, Pieter, Van Der Schueren, Jan, Mammoliti, Oscar, Conrath, Katja, and Andrews, Martin

Abstract

Cystic fibrosis (CF) is caused by mutations in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR). With the discovery of Ivacaftor and Orkambi, it has been shown that CFTR function can be partially restored by administering one or more small molecules. These molecules aim at either enhancing the amount of CFTR on the cell surface (correctors) or at improving the gating function of the CFTR channel (potentiators). Here we describe the discovery of a novel potentiator GLPG1837, which shows enhanced efficacy on CFTR mutants harboring class III mutations compared to Ivacaftor, the first marketed potentiator. The optimization of potency, efficacy, and pharmacokinetic profile will be described.

Published
2024
Full Text
View/download PDF

9. Isothiourea-Mediated Asymmetric O- to C-Carboxyl Transfer of Oxazolyl Carbonates: Structure-Selectivity Profiles and Mechanistic Studies

Author

Joannesse, Caroline, primary, Johnston, Craig P., additional, Morrill, Louis C., additional, Woods, Philip A., additional, Kieffer, Madeleine, additional, Nigst, Tobias A., additional, Mayr, Herbert, additional, Lebl, Tomas, additional, Philp, Douglas, additional, Bragg, Ryan A., additional, and Smith, Andrew D., additional

Published
2012
Full Text
View/download PDF

13. Structure-enantioselectivity effects in 3,4-dihydropyrimido[2,1-b]benzothiazole-based isothioureas as enantioselective acylation catalysts

Author

Belmessieri, Dorine, primary, Joannesse, Caroline, additional, Woods, Philip A., additional, MacGregor, Callum, additional, Jones, Caroline, additional, Campbell, Craig D., additional, Johnston, Craig P., additional, Duguet, Nicolas, additional, Concellón, Carmen, additional, Bragg, Ryan A., additional, and Smith, Andrew D., additional

Published
2011
Full Text
View/download PDF

16. ChemInform Abstract: N‐Heterocyclic Carbene Catalyzed Oxygen‐to‐Carbon Carbonyl Transfer of Indolyl and Benzofuranyl Carbonates.

Author

Thomson, Jennifer E., primary, Kyle, Andrew F., additional, Gallagher, Katherine A., additional, Lenden, Philip, additional, Concellon, Carmen, additional, Morrill, Louis C., additional, Miller, Andrew J., additional, Joannesse, Caroline, additional, Slawin, Alexandra M. Z., additional, and Smith, Andrew D., additional

Published
2008
Full Text
View/download PDF

20. IsothioureaCatalyzed Enantioselective Carboxy Group TransferWe thank the Royal Society ADS, the EPSRC C.J., and the Ministerio de Educación y Ciencia C.S. and C.C. for funding and the EPSRC Mass Spectrometry Centre. Prof. Edwin Vedejs is gratefully acknowledged for supplying an authentic sample of RTADMAP to allow unambiguous stereochemical assignments.

Author

Joannesse, Caroline, Johnston, CraigP., Concellón, Carmen, Simal, Carmen, Philp, Douglas, and Smith, AndrewD.

Abstract

No Abstract

Published
2009
Full Text
View/download PDF

22. Isothiourea-mediated asymmetric O- to C-carboxyl transfer of oxazolyl carbonates: structure-selectivity profiles and mechanistic studies.

Author

Joannesse C, Johnston CP, Morrill LC, Woods PA, Kieffer M, Nigst TA, Mayr H, Lebl T, Philp D, Bragg RA, and Smith AD

Subjects
Catalysis, Magnetic Resonance Spectroscopy, Molecular Structure, Stereoisomerism, Carbonates chemistry, Lewis Bases chemistry, Oxazoles chemistry, Pyrimidines chemistry, Thiourea chemistry
Abstract

The structural motif within a series of tetrahydropyrimidine-based isothioureas necessary for generating high asymmetric induction in the asymmetric Steglich rearrangement of oxazolyl carbonates is fully explored, with crossover and dynamic (19)F NMR experiments used to develop a mechanistic understanding of this transformation., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Published
2012
Full Text
View/download PDF

23. Structure-enantioselectivity effects in 3,4-dihydropyrimido[2,1-b]benzothiazole-based isothioureas as enantioselective acylation catalysts.

Author

Belmessieri D, Joannesse C, Woods PA, MacGregor C, Jones C, Campbell CD, Johnston CP, Duguet N, Concellón C, Bragg RA, and Smith AD

Subjects
Acylation, Amines chemistry, Catalysis, Molecular Structure, Stereoisomerism, Benzothiazoles chemistry, Thiourea chemistry
Abstract

The catalytic activity and enantioselectivity in the kinetic resolution of (±)-1-naphthylethanol with a range of structurally related 3,4-dihydropyrimido[2,1-b]benzothiazole-based catalysts is examined. Of the isothiourea catalysts screened, (2S,3R)-2-phenyl-3-isopropyl substitution proved optimal, giving good levels of selectivity in the kinetic resolution of a number of secondary alcohols (S values up to >100 at ~50% conversion). Low catalyst loadings (0.10-0.25 mol%) of the optimal isothiourea can be used to generate enantiopure alcohols (>99% ee) in good yields.

Published
2011
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results