Synthesis of Bioactive Compounds and Development of New Methodologies in Organic Synthesis
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
iBiTec-S / SCBM /LCB
Human resources
Marie-Pierre HECK, Group Leader
Thierry LE GALL, Group Leader
Juline ROULEAU, Postdoctoral Fellow
Véronique LEWIN, PhD Student
Research Programs
The synthesis of natural products and biologically active analogues is the main activity of our team. The properties of the synthesized compounds are evaluated in collaboration with biologists from the CEA (in particular from iBiTec-S) or other research organizations. We are particularly interested in antioxidant compounds (norbadione A, pulvinic acids, oxylipines), in antitumoral compounds (Annonaceae acetogenins, fatty acids, inhibitors of mannosidases) and in molecules able to be used in the treatment of infections such as influenza and HIV (inhibitors of glycosidases). We also develop new methods of synthesis used to carry out these projects. Thus, our recent work dealt particularly with metathesis reactions, the development of new non-metallic Lewis acids, the study of the reactivity of the boron compounds and silyl ketene acetals. The use of original, easily accessible synthons allowing to carry out new chemical transformations is also a privileged research orientation of our team.
©CEA/MP. Heck
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©CEA/MP. Heck
Key words
Organic synthesis, natural products, antioxidants, amino sugars, oxilipins, enzyme inhibitors, borated derivatives, metathesis reaction, Lewis acids.
Publications
Le Roux A, Josset E, Benzina S, Nadal B, Desage-El Murr M, Heurtaux B, Taran F, Denis J M, Le Gall T, Meunier S, Bischoff P. (2012). Evaluation of the Radioprotective Potential of the Polyphenol Norbadione A. Lett Drug Des Discov. 9, 48-53.
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.
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, 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.