Equipe Synthèse de Composés Bioactifs et Développement de Nouvelles Méthodologies en synthèse organique
Marie-Pierre HECK & Thierry LE GALL
CEA Saclay/Bât. 547
Tél: (+33) 1 69 08 37 03 (MCH)/(+33) 1 69 08 71 05 (TLG)
marie-pierre.heck@cea.fr/thierry.legall@cea.fr
CEA Saclay/Bât. 547
Tél: (+33) 1 69 08 37 03 (MCH)/(+33) 1 69 08 71 05 (TLG)
marie-pierre.heck@cea.fr/thierry.legall@cea.fr
L'équipe s'intéresse principalement à la préparation de produits naturels et d'analogues biologiquement actifs.
Moyens humains
Marie-Pierre HECK, Chercheuse
Thierry LE GALL, Chercheur
Juline ROULEAU, Post-doctorant
Véronique LEWIN, Doctorante
Thèmes de recherche
La synthèse de produits naturels et d’analogues biologiquement actifs constitue l'activité principale de notre équipe. Les propriétés des composés préparés sont évaluées en collaboration avec des biologistes du CEA (notamment, de l’iBiTec-S) ou d’autres organismes de recherche. Nous nous intéressons particulièrement aux composés antioxydants (norbadione A, acides pulviniques, oxylipines), aux molécules anti-tumorales (acétogénines d’Annonaceae, acides gras, inhibiteurs de mannosidases) et à des molécules pouvant être employées dans le traitement d’infections comme la grippe et le VIH (inhibiteurs de glycosidases).
Nous développons également de nouvelles méthodes de synthèse pour mener à bien ces projets. Ainsi, nos travaux récents ont concerné particulièrement les réactions de métathèse, la mise au point de nouveaux acides de Lewis non métalliques, l’étude de la réactivité des dérivés borés et des acétals de cétènes silylés. L'emploi de synthons originaux facilement accessibles permettant de réaliser de nouvelles transformations chimiques est également un axe de recherche privilégié de notre équipe.
©CEA/MP. Heck-T. Le Gall
Nous développons également de nouvelles méthodes de synthèse pour mener à bien ces projets. Ainsi, nos travaux récents ont concerné particulièrement les réactions de métathèse, la mise au point de nouveaux acides de Lewis non métalliques, l’étude de la réactivité des dérivés borés et des acétals de cétènes silylés. L'emploi de synthons originaux facilement accessibles permettant de réaliser de nouvelles transformations chimiques est également un axe de recherche privilégié de notre équipe.
 |
©CEA/MP. Heck-T. Le Gall
Mots-clés
synthèse organique, produits naturels, antioxydants, sucres aminés, oxylipines, inhibiteurs d'enzyme, dérives borés, réaction de méthatèse, acides de Lewis.
Publications
Huber G, Legrand F X, Lewin V, Baumann D, Heck M P, Berthault P. (2011). Interaction of Xenon with Cucurbit[5]uril in Water. ChemPhysChem. 12, 1053-1055.
Le Roux A, Meunier S, Le Gall T, Denis J M, Bischoff P, Wagner A. (2011). Synthesis and Radioprotective Properties of Pulvinic Acid Derivatives. ChemMedChem. 6, 561-569.
Le Roux A, Kuzmanovski I, Habrant D, Meunier S, Bischoff P, Nadal B, Thetiot-Laurent S A L, Le Gall T, Wagner A, Novic M. (2011). Design and Synthesis of New Antioxidants Predicted by the Model Developed on a Set of Pulvinic Acid Derivatives. J Chem Inf Model. 51, 3050-3059.
Nadal, B, Rouleau J, Besnard H, Thuery P, Le Gall T. (2011). Synthesis of pulvinones via tandem Dieckmann condensation-alkoxide alpha-elimination. Tetrahedron. 67, 2605-2611.
Capra J, Le Gall T. (2010). Oxidative Conversion of Imines into 2-Azadienes. Synlett. 3, 441-444.
Heck M P, Matt C, Wagner A, Toupet L, Mioskowski C. (2010). New Cyclotrimerization of Aldehydes to Cyclopentenone or Tetrahydrofuran Induced by Dibromotriphenylphosphorane. Eur J Org Chem. 966-971.
Korovitch A, Mulon L B, Souchon V, Leray I, Valeur B, Mallinger A, Nada B, Le Gall T, Lion C, Ha-Duong N T, Chahine Jmeh. (2010). Norbadione A: Kinetics and Thermodynamics of Cesium Uptake in Aqueous and Alcoholic Media. J. Phys. Chem. B. 114, 12655-12665.
Mallinger A, Nadal B, Chopin N, Le Gall T. (2010). One-Pot Synthesis of 3-Aryltetramic Acids. Eur J Org Chem. 1142-1148.
Nadal B, Thetiot-Laurent S AL, Pin S, Renault JP, Cressier D, Rima G, Le Roux A, Meunier S, Wagner A, Lion C, Le Gall T. (2010). Synthesis and antioxidant properties of pulvinic acids analogues. Bioorg Med Chem. 18, 7931-7939.
Thetiot-Laurent S A L, Nadal B, Le Gall T. (2010). Synthesis of Bis(tetronic acid)s via Double Dieckmann Condensation. Synthesis. 1697-1701.
Habrant D, Poigny S, Segur-Derai M, Brunel Y, Heurtaux B, Le Gall T, Strehle A, Saladin R, Meunier S, Mioskowski C, Wagner A. (2009). Evaluation of Antioxidant Properties of Monoaromatic Derivatives of Pulvinic Acids. J Med Chem. 52, 2454-2464.
Nadal B, Thuery P, Le Gall T. (2009). Synthesis of vulpinic acids from dimethyl tartrate. Tetrahedron Lett. 50, 2430-2433.
Bourdreux Y, Nowaczyk S, Billaud C, Mallinger A, Willis C, Murr MD, Toupet L, Lion C, Gall TL, Mioskowski C. (2008). Total Synthesis of Norbadione A. J Org Chem. 73, 22-26.
Gratien J, Heck MP, Mioskowski C. (2008). C-2 Epimerization of aldonolactones promoted by magnesium iodide: A new way towards non-enzymatic epimerization. Carbohydr Res. 343, 18-30.
Mallinger A, Le Gall T, Mioskowski C. (2008). One-pot synthesis of tetronic acids from esters. Synlett. 3, 386-388.
Mallinger A, Le Gall T, Mioskowski C. (2008). 3-Aryltetronic Acids: Efficient Preparation and Use as Precursors for Vulpinic Acids. J Org Chem. 74, 1124-9.
Tailford LE, Offen WA, Smith NL, Dumon C, Morland C, Gratien J, Heck MP, Stick RV, Blériot Y, Vasella A, Gilbert HJ, Davies GJ. (2008). Structural and biochemical evidence for a boat-like transition state in beta-mannosidases. Nat Chem Biol. 4, 306-12.
Bourdreux Y, Nowaczyk S, Billaud C, Mallinger A, Willis C, Murr MD, Toupet L, Lion C, Gall TL, Mioskowski C. (2007).Total Synthesis of Norbadione A. J Org Chem. 73, 22-26.
Brossat M, Heck MP, Mioskowski C. (2007).Bistrimethylsilylpropargylic Ether: A Versatile Ambident Synthon to Access Substituted Allenyne Ethers and alpha-Substituted Bispropargylic Alcohols. J Org Chem. 72, 5941-5941.
Willis C, Bodio E, Bourdreux Y, Billaud C, Le Gall T, Mioskowski C. (2007). Flexible synthesis of vulpinic acids from tetronic acid. Tetrahedron Lett. 48, 6421-6424.
Le Roux A, Meunier S, Le Gall T, Denis J M, Bischoff P, Wagner A. (2011). Synthesis and Radioprotective Properties of Pulvinic Acid Derivatives. ChemMedChem. 6, 561-569.
Le Roux A, Kuzmanovski I, Habrant D, Meunier S, Bischoff P, Nadal B, Thetiot-Laurent S A L, Le Gall T, Wagner A, Novic M. (2011). Design and Synthesis of New Antioxidants Predicted by the Model Developed on a Set of Pulvinic Acid Derivatives. J Chem Inf Model. 51, 3050-3059.
Nadal, B, Rouleau J, Besnard H, Thuery P, Le Gall T. (2011). Synthesis of pulvinones via tandem Dieckmann condensation-alkoxide alpha-elimination. Tetrahedron. 67, 2605-2611.
Capra J, Le Gall T. (2010). Oxidative Conversion of Imines into 2-Azadienes. Synlett. 3, 441-444.
Heck M P, Matt C, Wagner A, Toupet L, Mioskowski C. (2010). New Cyclotrimerization of Aldehydes to Cyclopentenone or Tetrahydrofuran Induced by Dibromotriphenylphosphorane. Eur J Org Chem. 966-971.
Korovitch A, Mulon L B, Souchon V, Leray I, Valeur B, Mallinger A, Nada B, Le Gall T, Lion C, Ha-Duong N T, Chahine Jmeh. (2010). Norbadione A: Kinetics and Thermodynamics of Cesium Uptake in Aqueous and Alcoholic Media. J. Phys. Chem. B. 114, 12655-12665.
Mallinger A, Nadal B, Chopin N, Le Gall T. (2010). One-Pot Synthesis of 3-Aryltetramic Acids. Eur J Org Chem. 1142-1148.
Nadal B, Thetiot-Laurent S AL, Pin S, Renault JP, Cressier D, Rima G, Le Roux A, Meunier S, Wagner A, Lion C, Le Gall T. (2010). Synthesis and antioxidant properties of pulvinic acids analogues. Bioorg Med Chem. 18, 7931-7939.
Thetiot-Laurent S A L, Nadal B, Le Gall T. (2010). Synthesis of Bis(tetronic acid)s via Double Dieckmann Condensation. Synthesis. 1697-1701.
Habrant D, Poigny S, Segur-Derai M, Brunel Y, Heurtaux B, Le Gall T, Strehle A, Saladin R, Meunier S, Mioskowski C, Wagner A. (2009). Evaluation of Antioxidant Properties of Monoaromatic Derivatives of Pulvinic Acids. J Med Chem. 52, 2454-2464.
Nadal B, Thuery P, Le Gall T. (2009). Synthesis of vulpinic acids from dimethyl tartrate. Tetrahedron Lett. 50, 2430-2433.
Bourdreux Y, Bodio E, Willis C, Billaud C, Le Gall T, Mioskowski C. (2008). Synthesis of vulpinic and pulvinic acids from tetronic acid. Tetrahedron. 64, 8930-8937.
Bourdreux Y, Nowaczyk S, Billaud C, Mallinger A, Willis C, Murr MD, Toupet L, Lion C, Gall TL, Mioskowski C. (2008). Total Synthesis of Norbadione A. J Org Chem. 73, 22-26.
Gratien J, Heck MP, Mioskowski C. (2008). C-2 Epimerization of aldonolactones promoted by magnesium iodide: A new way towards non-enzymatic epimerization. Carbohydr Res. 343, 18-30.
Mallinger A, Le Gall T, Mioskowski C. (2008). One-pot synthesis of tetronic acids from esters. Synlett. 3, 386-388.
Mallinger A, Le Gall T, Mioskowski C. (2008). 3-Aryltetronic Acids: Efficient Preparation and Use as Precursors for Vulpinic Acids. J Org Chem. 74, 1124-9.
Tailford LE, Offen WA, Smith NL, Dumon C, Morland C, Gratien J, Heck MP, Stick RV, Blériot Y, Vasella A, Gilbert HJ, Davies GJ. (2008). Structural and biochemical evidence for a boat-like transition state in beta-mannosidases. Nat Chem Biol. 4, 306-12.
Bourdreux Y, Nowaczyk S, Billaud C, Mallinger A, Willis C, Murr MD, Toupet L, Lion C, Gall TL, Mioskowski C. (2007).Total Synthesis of Norbadione A. J Org Chem. 73, 22-26.
Brossat M, Heck MP, Mioskowski C. (2007).Bistrimethylsilylpropargylic Ether: A Versatile Ambident Synthon to Access Substituted Allenyne Ethers and alpha-Substituted Bispropargylic Alcohols. J Org Chem. 72, 5941-5941.
Willis C, Bodio E, Bourdreux Y, Billaud C, Le Gall T, Mioskowski C. (2007). Flexible synthesis of vulpinic acids from tetronic acid. Tetrahedron Lett. 48, 6421-6424.
Mondière R, Goddard JP, Huiban M, Carrot G, Le Gall T, Mioskowski C. (2006). Boron-mediated polymerization of ylides derived from allylic arsonium salts: influence of the double bond substitution on the outcome. Chem Commun. 723-725.
Heurtaux B, Lion C, Le Gall T, Mioskowski C. (2005). Uncatalyzed Reaction of Silyl Ketene Acetals with Oxalyl Chloride: A Straightforward Preparation of Symmetrical Pulvinic Acids J Org Chem. 70, 1474-1477.
Kuad P, Borkovec M, Desage-El Murr M, Le Gall T, Mioskowski C, Spiess B. (2005). Inframolecular Protonation Process of Norbadione A: Influence of the Ionic Environment and Stereochemical Consequences. J Am Chem Soc. 127, 1323-1333.
Meunier S, Hanedanian M, Desage-El Murr M, Nowaczyk S, Le Gall T, Pin S, Renault JP, Boquet D, Créminon C, Mioskowski C, Taran F. (2005). High-Throughput Evaluation of Antioxidant and Pro-oxidant Activities of Polyphenols with Thymidine Protection Assays. Chembiochem. 6, 1234-1241.
Heck MP, Vincent SP, Murray BW, Bellamy F, Wong CH, Mioskowski C. (2004). Cyclic Amidine Sugars as Transition-State Analogue Inhibitors of Glycosidases: Potent Competitive Inhibitors of Mannosidases. J Am Chem Soc. 126, 1971-1979.
Meunier S, Desage-El Murr M, Nowaczyk S, Le Gall T, Pin S, Renault JP, Boquet D, Créminon C, Saint-Aman E, Valleix A, Taran F, Mioskowski C. (2004). A powerful antiradiation compound revealed by a new high-throughput screening method. Chembiochem. 5, 832-840.
Mondière R, Goddard JP, Carrot G, Le Gall T, Mioskowski C. (2004). Synthesis of Poly(2-substituted-1-propenylene)s from Allylic Arsonium Ylides. Macromolecules. 38, 663-668.
Prestat G, Baylon C, Heck MP, Grasa GA, Nolan SP, Mioskowski C. (2004). New Strategy for the Construction of a Monotetrahydrofuran Ring in AnnonaceousAcetogenin Based on a Ruthenium Ring-Closing Metathesis: Application to the Synthesis of Solamin. J Org Chem. 69, 5770-5773.
Billaud C, Goddard JP, Le Gall T, Mioskowski C. (2003). Preparation of alcohols from sulfones and trialkylboranes Tetrahedron Lett. 44, 4451-4454.
Desage-El Murr M, Nowaczyk S, Le Gall T, Mioskowski C, Amekraz B, Moulin C. (2003). Norbadione A: synthetic approach to the bis(pulvinic acid) moiety and cesium-complexation studies. Angew Chem Int Ed Engl. 42, 1289-1293.
Goddard JP, Lixon P, Le Gall T, Mioskowski C. (2003). Chain elongations by three carbon atoms at a time in the boron-catalyzed polymerization of methallyltriphenylarsonium ylide. J Am Chem Soc. 125, 9242-9243.
Jafarpour L, Heck MP, Baylon C, Lee MH, Mioskowski C, Nolan SP. (2002). Preparation and activity of recyclable polymer-supported ruthenium olefin metathesis catalysts. Organometallics. 21, 671-679.
Spagnol G, Heck MP, Nolan SP, Mioskowski C. (2002). Efficiency of a ruthenium catalyst in metathesis reactions of sulfur containing compounds. Org Lett. 4, 1767-1770.
Heck MP, Baylon C, Nolan SP, Mioskowski C. (2001). Triple ring closing metathesis reaction : synthesis of adjacent cyclic ethers. Org Lett. 3, 1989-1991.
Leroux ML, Le Gall T, Mioskowski C. (2001). Enantioselective synthesis of alpha,alpha-disubstituted amines from nitroalkenes. Tetrahedron Asymmetry. 12, 1817-1823.
Prestat G, Baylon C, Heck MP, Mioskowski C. (2000). Lewis acid-catalyzed regiospecific opening of vinyl epoxides by alcohols. Tetrahedron Lett. 41, 3829-3832.
Baylon C, Prestat G, Heck MP, Mioskowski C. (2000). Synthesis of (--)-(4R,5R)-muricatacin using a regio- and stereospecific ring-opening of a vinyl epoxide. Tetrahedron Lett. 41, 3833-3835.
Charoy L, Valleix A, Toupet L, Le Gall T, Pham van Chuong P, Mioskowski C. (2000). Synthesis of benzylcyanoborane adducts of amines and separation of their enantiomers; S(N)2 substitution at boron atom. Chem Commun. 2275-2276.
Goddard JP, Le Gall T, Mioskowski C. (2000). Preparation of alcohols from alkenes via the homologation of boronates with (trimethylsilyl)diazomethane. Org Lett. 2, 1455-1456.
Lucet D, Heyse P, Gissot A, Le Gall T, Mioskowski C. (2000). Synthesis of the diastereomers of dethiobiotin using the conjugate addition of 4-phenyloxazolidin-2-one to a nitroalkene. Eur J Org Chem. 3575-3580.