Thématiques du groupe

 

A – Chimie pour le Vivant

Nouveaux ligands du système nerveux central : dérivés de la cytisine

Depuis plusieurs années, le groupe étudie la chimie de la cytisine. Après avoir développé des approches méthodologiques pour son radiomarquage au carbone-11 (demi-vie : 20 min) et synthétisé des dérivés fluorés et marqués au fluor-18 (demi-vie: 110 min) pour des études in vivo des récepteurs nicotiniques, par tomographie par émission de positons (TEP), les recherches actuelles sont orientées vers la fonctionnalisation originale de la cytisine et la synthèse d’analogues pour leurs évaluations biologiques.

 

B – Chimie pour le développement durable

Parmi les différents « principes » de la chimie pour le développement durable, le groupe concentre ses efforts sur :

• la recherche de réactions catalytiques organométalliques afin de réaliser de façon efficace des réactions en utilisant de faibles quantités de réactifs, limitant ainsi les déchets et les dépenses énergétiques ;
• l’organocatalyse (décarboxylations-protonations énantiosélectives, réaction de Nazarov) permettant de s’affranchir des métaux, et de réaliser des réactions dans des conditions douces ;
• l’utilisation de réactifs ou catalyseurs facilement préparés et peu coûteux incluant des dérivés des alcaloïdes du quinquina ;
• la recyclabilité du catalyseur.

 

A – Chemistry for Life. New ligands of Central Nervous System receptors

For the last ten years, our group has studied the chemistry of cytisine mainly to provide radiotracers for in vivo studies of nicotinic receptors using positron emission tomography (PET). Thus, methodological approaches for cytisine radiolabelling with carbon-11 (half-life: 20 min) and synthesis of fluorinated derivatives including labelled with fluorine-18 (half-life: 110 min) have been developed. The current research is directed towards the functionalisation of the original cytisine and synthesis of analogues for biological assays.

• Cytisine.
• Synthesis of substituted cytisine derivatives and labelling with fluorine-18.
• Rapid synthesis of amides and lactams. Applications in carbon-11 chemistry.
• Carbon-6 functionalisation of cytisine.

B – Chemistry for sustainable development

Among the twelve « Green Chemistry Principles » the group focuses its efforts on :

• the search for catalytic reactions mediated by transition metal in order to achieve efficient transformations using small amounts of reagents, reducing waste and energy costs;
• the organocatalysis (enantioselective decarboxylative protonation, Nazarov reaction), a metal-free approach using mild conditions;
• the use of reagents or catalysts easily prepared and inexpensive;
• the recyclability of the catalyst.

1 – Organometallic catalysis

• N-(3-arylamino)pyrrolidines and piperidines, ligands for asymmetric catalysis

2 – Organocatalysis

• Enantioselective decarboxylative protonation
• Nazarov reaction
• Mannich reaction

3 – Organocatalysts

• Cinchona alkaloids
• 3-Trifluoromethanesulfonamido-pyrrolidine
• beta-Proline

Sulfonimides versus ketosulfonamides as epoxidized imidazolium counterions: towards a new generation of ionic liquid monomers
Chardin, C.; Durand, A.; Jarsale, K.; Rouden, J.; Livi, S.; Baudoux, J.
New Journal of Chemistry, 2021, 45 (6), 2953-2957.
doi: 10.1039/d0nj05126h

New Epoxy Thermosets Derived from a Bisimidazolium Ionic Liquid Monomer: An Experimental and Modeling Investigation
Radchenko, A. V.; Chabane, H.; Demir, B.; Searles, D. J.; Duchet-Rumeau, J.; Gerard, J.-F.; Baudoux, J.; Livi, S.
ACS Sustainable Chemistry & Engineering, 2020, 8 (32), 12208-12221.
doi: 10.1021/acssuschemeng.0c03832

Cycloaliphatic epoxidized ionic liquids as new versatile monomers for the development of shape memory PIL networks by 3D printing
Radchenko, A. V.; Duchet-Rumeau, J.; Gerard, J.-F.; Baudoux, J.; Livi, S.
Polymer Chemistry, 2020, 11 (34), 5475-5483.
doi: 10.1039/d0py00704h

Phenysilane and Silicon Tetraacetate: Versatile Promotors for Amide Synthesis.
Morisset, E.; Chardon, A.;  Rouden, J.; Blanchet, J.
European Journal of Organic Chemistry, 2020, 2020 (3), 388-392.
doi: 10.1002/ejoc.201901660
hal-02962274

Self-Catalyzed Coupling between Bronsted-Acidic Imidazolium Salts and Epoxy-Based Materials: A Theoretical/Experimental Study
Perchacz, M.; Matejka, L.; Konefal, R.; Seixas, L.; Livi, S.; Baudoux, J.; Benes, Hynek; Donato, Ricardo K.
ACS Sustainable Chemistry & Engineering, 2019, 7 (23), 19050-19061.
DOI: 10.1021/acssuschemeng.9b04810

The synthesis and characterization of giant Calixarenes
Guérineau, V.; Rollet, M.; Viel, S.; Lepoittevin, B.; Costa, L.; Saint-Aguet, P.; Laurent, R.; Roger, P.; Gigmes, D.; Martini, C.; Huc, V.
Nature Communications, 2019, 10 (113) on line
DOI: 10.1038/s41467-018-07751-4
hal-01998267v1

Hydrophobization of chitosane films by surface grafting with fluorinated polymer brushes
Lepoittevin, B.; Elzein, T.; Dragoe, D.; Bejjani, A.; Lemée, F.;  Levillain, J.; Bazin, P.; Roger, P.; Dez, I.
Carbohydrate Polymers, 2019, 205, 437-446.
DOI : 10.106/j.carbpol.2018.10.044

Catalytic and metal-free intramolecular hydroalkoxylation of alkynes
Jean, A.; Rouden, J.; Maddaluno, J.; De Paolis, M.; Blanchet, J.
Tetrahedron Lett., Elsevier, 2019, 60 (7), pp.534-537.
DOI: 10.1016/j.tetlet.2019.01.020
hal-02019126, version 1

Access to Anti or Syn 2-Amino-1,3-diol Scaffolds from a Common Decarboxylative Aldol Adduct
Chaumont, P.; Baudoux, J.; Maddaluno, J.; Rouden, J.; Harrison-Marchand A.
J. Org. Chem. 2018, 83 (15), pp.8081-8091
DOI: 10.1021/acs.joc.8b00901
hal-02019133, version 1

DMDO as a valuable oxidant for the synthesis of polyfunctionnal aromatic imidazolium skeletons bearing epoxides
Chardin, C.; Rouden, J.; Livi, S.; Baudoux, J.
Green Chem. 2017, (accepté le 14 septembre et publié online)
DOI: 10.1039/C7GC02372C

Metal free, borinic acid-catalyzed phosphine oxides, sulfoxides and N-oxides reductions
Chardon, A.; Rouden, J.; Blanchet, J.
ChemCatChem 2017, (accepté le 28 août et publié online)
DOI: 10.1002/cctc.201700986

Thioamide-subtituted cinchona alkaloid derivatives as efficient organocatalysts
Singjunla, Y.; Pigeaux, M.; Laporte, R.; Baudoux, J.; Rouden,J.
Eur. J. Org. Chem. 2017, 4319-4323.
DOI: 10.1002/ejoc.201700870

Straightforward and stereoselective synthesis of a,ß-diamino acid derivatives by an organocatalyzed decarboxylative Mannich reaction
Singjunla, Y.; Baudoux, J.; Rouden, J.
Eur. J. Org. Chem. 2017, 3240-3243.
DOI:10.1002/ejoc.201700468

Gaining Insight Into Reactivity Differences Between Malonic Acid Half Thioester (MAHT) and Malonic Acid Half Oxyesters (MAHO)
Bew, S. P.; Stephenson, G. R.; Rouden, J.; Godemert, J.; Seylani, H.; Martinez-Lozano, L. A.
Chem.-Eur. J. 2017, 23, 4557-4569.
DOI:10.1002/chem.201605148

Borinic acid catalysed hydrosilanes reduction of tertiary amides: a mild and chemoselective synthesis of amines
Chardon, A.; Mohy El Dine, T.; Legay, R.; De Paolis, M.; Rouden, J.; Blanchet, J.
Chem.-Eur. J. 2017, 23, 2005-2009.
DOI:10.1002/chem.201604802

Stereoselective synthesis of dehydroamino acids using malonic acid half oxyester and aromatic aldehydes
Singjunla, Y.; Colombano, S.; Baudoux, J.; Rouden, J.
Tetrahedron 2016, 72, 2369-2375.
DOI: 10.1016/j.tet.2016.03.043

Towards a universal organocatalyst for the synthesis of enantioenriched phenylalanine derivatives by enantioselective decarboxylative protonation
Pigeaux, M.; Laporte, R.; Harrowven, D. C.; Baudoux, J.; Rouden, J.
Tetrahedron Lett. 2016, 57, 4599-4603.
DOI: 0.1016/j.tetlet.2016.09.001

Formamide synthesis through borinic acid catalysed transamidation under mild conditions
Mohy El Dine, T.; Evans, D.; Rouden, J.; Blanchet, J.
Chem. Eur. J., 2016, 22 (17), 5894-5898.
DOI: 10.1002/chem.201600234

Boronic acid catalysed peptide synthesis
Mohy El Dine, T.; Rouden, J.; Blanchet, J.
Chem. Commun. 2015, 51 (89), 16084-16087.
DOI: 10.1039/C5CC06177F

Catalytic chemical amide synthesis at room temperature: one more step toward peptide synthesis
Mohy El Dine, T.; Erb, W.; Berhault, Y.; Rouden, J.; Blanchet, J.
J. Org. Chem. 2015, 80 (9), 4532-4544
DOI: 10.1021/acs.joc.5b00378

Bioinspired, base- and metal-free, mild decarboxylative aldol activation of malonic acid half thioesters under phase-transfer reaction conditions
Bew, S. P.; Stephenson, G. R.; Rouden, J.; Ashford, P.-A.; Bourane, M.; Charvet, A.; Dalstein, V. M. D.; Jauseau, R.; Hiatt-Gibson, G.D.; Martinez-Lozano, L. A.
Adv. Synth. Catal. 2015, 357 (6), 1245-1247.
DOI: 10.1002/adsc.201400915

An organocatalytic access to spiro[4.5]decanes and spiro[4.6]undecanes containing aminolactones and 3-aminopyrrolidines
Cormier, M.; Chardon, A.; Blanchet, J.; Rouden, J.; Maddaluno, J.; De Paolis, M.
Synthesis, 2015, 47(17), 2549-2553.
DOI: 10.1055/s-0034-138014

An easy route to (hetero)arylboronic acids
Erb, W.; Hellal, A.; Albini, M.; Rouden, J.; Blanchet, J.
Chemistry: A European Journal 2014, 20 (22), 6608-6612.
DOI: 10.1002/chem.201402487

(-)-Cytisine and derivatives: synthesis, reactivity and applications
Rouden, J.; Lasne, M.-C. ; Blanchet, J.; Baudoux, J.
Chem. Rev. 2014, 114, 712-778.
DOI: 10.1021/cr400307e
hal-00909872

Direct synthesis of -hydroxy-amino-acids via diastereoselective decarboxylative aldol reaction
Singjunla, Y.; Baudoux, J.; Rouden, J.
Org. Lett. 2013, 15, 1770-1773.

An organocatalytic route to 2-heteroarylmethylene decorated N-arylpyrroles
Jean, A.; Blanchet, J.; Rouden, J.; Maddaluno, J.; Paolis, M. D.
Belstein J. Org. Chem. 2013, 9, 1480-1486.
DOI: 10.3762/bjoc.9.168
HAL: hal-00871122

Stereoselective access to heteroarylmethylene-substituted pyrrolidines: fully organocatalytic Mannic/hydroamination reactions
Jean, A.; Blanchet, J.; Rouden, J.; Maddaluno, J.; DePaolis, M.
Chem. Commun. 2013, 49, 1651-1653.
DOI: 10.1039/c2cc38954a
HAL: hal-00871123

Role of cationisation and multimers formation for diastereomers differentiation by ion mobility-mass spectrometry
Domalain, V.; Tognetti, V.; Hubert-Roux, M.; Lange, C. M.; Joubert, L.; Baudoux, J.; Rouden, J.; Afonso, C.
J. Am. Soc. Mass Spectrom. 2013, 24, 1437-1445.

Malonic acid half oxyesters and thioesters: solvent-free synthesis and DFT analysis of their enols
Bew, S.; Stephenson, G. R.; Rouden, J.; Martinez-Lozano, L.; Seylani, H.
Org. Lett. 2013, 15, 3805-3807.
DOI: 10.1021/ol400804b

Synthesis of a new chiral sulfonic acid
Das, J.; Cavelier, F. L.; Rouden, J.; Blanchet, J.
Synthesis 2012, 44 (9), 1349-1352.

Expanding the scope of the direct regiospecific asymmetric aldol reaction to enones and dienones catalysed by a binol-derived Bronsted acid
Das, J.; Cavelier, F. L.; Rouden, J.; Blanchet, J.
Eur. J. Org Chem. 2011, 6628-6631.

Metal Free SN2′ decarboxylative rearrangement of beta-ketoesters
Bizet, V.; Lefebvre, V.; Baudoux, J.; Lasne, M.-C.; Boulange, A.; Leleu, S.; Franck, F.; Rouden, J.
Eur. J. Org. Chem. 2011, (22), 4170-4175.

Chiral 3-aminopyrrolidines as a rigid diamino scaffold for organocatalysis and organometallic chemistry
Pouliquen, M.; Blanchet, J.; Paolis, M. D.; Devi, B. R.; Rouden, J.; Lasne, M.-C.; Maddaluno, J.
Tetrahedron: Asymmetry 2010, 21, (11-12), 1511-1521.

Bronsted acid catalyzed asymmetric aldol reaction: a complementary approach to enamine catalysis
Pousse, G.; Cavelier, F. ; Humphreys, L.; Rouden, J.; Blanchet, J.
Org. Lett. 2010, 12, 3582-3585.

Synthesis of P,N-2,2′-biphenyl derivatives with central chirality
Jean, L.; Pouliquen, M.; Blanchet, J.; Lasne, M.-C.; Rouden, J.
Science China-Chemistry 2010, 53, 1907-1913.

Identification of 9-fluoro substituted (-)-Cytisine derivatives as ligands with high affinity for nicotinic receptors
Houllier, N.; Gopisetti, J.-M.; Lestage, P.; Lasne, M.-C.; Rouden, J.
Bioorg. Med. Chem. Lett. 2010, 20, 6667-6670.

Synthesis of a cytisine/epibatidine hybrid: a radical approach
Houillier, N.; Lasne, M.-C.; Bureau, R.; Lestage, P.; Rouden, J.
Tetrahedron 2010, 66, 9231-9241.

One-pot hydroxyl activation/carbon-carbon bond forming sequence using a cooperative Brønsted base/Brønsted acid binary system
Devineau, A.; Pousse, G.; Taillier, C.; Blanchet, J.; Rouden, J.; Dalla, V.
Adv. Synth. Catal. 2010, 352, 2881-2886.

Environmentally benign metal-free decarboxylative aldol and Mannich reactions
Baudoux, J.; Lefebvre, P.; Legay, R.; Lasne, M.-C.; Rouden, J.
Green Chem. 2010, 12, 252-259.

Vers une chimie moléculaire verte
Campagne, J.-M.; Agbossou, F.; Ayad, T.; Baudoin, O.; Buono, G.; Chataigner, I.;  Crévisy, C.;  Dez, I.; Donnard, M.; Fache, F.;Feasson, C.; Gaumont, A.-C.; Giordano, L.; Hesemann, P.; Marsais, F.; Mauduit, M.; Michelet, V.; Mortreux, A.; Phansavath, P.; Piva, O.;  Roblin, J. P.; Rouden, J.; Taillefer, M.; Toullec, P. Y.;  Tschamber T.; Vidal, V.
L’actualité chimique 2010, 338-339, 15-27.

Desymmetrization of a meso-allylic acetal by enantioselective conjugate elimination
L. Xu, T. Regnier, L. Lemiègre, P. Cardinael, J.-C. Combret, J.-P. Bouillon, J. Blanchet, J. Rouden, A. Harrison-Marchand, J. Maddaluno
Organic Letters 2008, 10, 729-732.

3-Trifluoromethanesulfonamido-pyrrolidine: A general organocatalyst for anti-selective Mannich reactions
M. Pouliquen, J. Blanchet, M.-C. Lasne, J. Rouden
Organic Letters 2008, 10, 1029-1032.

Asymmetric malonic and acetoacetic acid syntheses – A century of enantioselective decarboxylative protonations
J. Blanchet, J Baudoux, M. Amere, M.-C. Lasne, J. Rouden
European Journal of Organic Chemistry 2008, 5493-5506.

New Trends in Molecular Imaging of Tumor Angiogenesis In vitro and in vivo Metalloprotease Imaging: an Overview
T. Berthelot, M.-C. Lasne, G. Déléris
Anti-cancer agents in Medicinal Chemistry (ex « Current Med. Chem. Anti-cancer agents ») 2008, 8, 497-522.

4-Toluenesulfonic acid: an environmentally benign catalyst for Nazarov
 cyclizations
M. Amere, J. Blanchet, M.-C. Lasne, J. Rouden
Tetrahedron Letters 2008, 49, 2541-2545.

NMR in chiral polypeptide liquid crystals: the problem of amines
A. Solgadi, L. Jean, M.-C. Lasne, J. Rouden, J. Courtieu, A. Meddour
Tetrahedron: Asymmetry, 2007, 18, 1511-1516.

Modified Julia fluoroolefination: selective preparation of
 fluoroalkenoates
E. Pfund, C. Lebargy, J. Rouden, T. Lequeux
Journal of Organic Chemistry 2007, 72, 7871-7877.

Origin of the detrimental effect of lithium halides on an enantioselective
 nucleophilic alkylation of aldehydes
F. Paté, N. Duguet, H. Oulyadi, A. Harrison-Marchand, C. Fressigné, J.-Y. Valnot, M.-C. Lasne, J. Maddaluno
Journal of Organic Chemistry 2007, 72, 6982-6991.

A simple and efficient synthesis of new mono- and bis([1,2,4]-oxadiazol)-benzaldehyde building blocks
F. Crestey, C. Lebargy, M.-C. Lasne, C. Perrio
Synthesis 2007, 3406-3410.

Palladium-mediated N-arylation of heterocyclic diamines: insights into the origin of an unusual chemoselectivity
N. Cabello-Sanchez, L. Jean, J. Maddaluno, M.-C. Lasne, J. Rouden
Journal of Organic Chemistry 2007, 72, 2030-2039.

A rapid and convenient synthesis of beta-proline
J. Blanchet, M. Pouliquen, M.-C. Lasne, J. Rouden
Tetrahedron Letters 2007, 48, 5727-5730.

Functionalization through lithiation of (S)-N-(1-phenylpropyl)-2-phenylquinoline-4-carboxamide. Application to the labeling with carbon-11 of NK-3 receptor antagonist SB 222200
I. Bennacef, C. Perrio, M.-C. Lasne, L. Barre
Journal of Organic Chemistry 2007, 72, 2161-2165.
Highly enantioselective decarboxylative protonation of alpha-aminomalonates mediated by thiourea cinchona alkaloid derivatives: access to both enantiomers of cyclic and acyclic alpha-aminoacids
M. Amere, M.-C. Lasne, J. Rouden
Organic Letters, 2007, 9, 2621-2624.

Organocatalyzed route to enantioenriched pipecolic esters: decarboxylation of an aminomalonate hemiester
T. Seitz, J. Baudoux, H. Bekolo, D. Cahard, J.-C. Plaquevent, M.-C. Lasne, J. Rouden
Tetrahedron, 2006, 62, 6155-6165.

Oxidation of aromatic lithium thiolates into sulfinate salts: an attractive entry to aryl sulfones labeled with carbon-11
C. Martin, F. Sandrinelli, C. Perrio, S. Perrio, M.-C. Lasne
Journal of Organic Chemistry 2006, 71, 210-214.

Regio-and diastereoselective functionalization of (-)-cytisine
N. Houllier, S. Gouault, M.-C. Lasne, J. Rouden
Tetrahedron 2006, 62, 11679-11686.

Aziridinium from N, N-dibenzyl serine methyl ester: synthesis of enantiomerically pure alpha-amino and alpha-beta-diamino esters
C. Couturier, J. Blanchet, T. Schlama, J. Zhu
Org. Lett. 2006, 8, 2183-2186.

Reactivity of (-) cytisine and derivatives towards palladium salts. X-ray characterization of a new palladium complex of (-)-cytisine
S. Bouquillon, J. Rouden, J. Muzart, M.-C. Lasne, M. Hervieu, A. Leclaire, B. Tinant
Comptes Rendus Chimie 2006, 9, 1301-1308.

INTERNATIONALES
Pr T.Ooi (Nagoya, Japon)
Pr G. R. Stephenson (Norwich, UK)
Pr D. C. Harrowven ( Southampton, UK)

 

NATIONALES
Dr Wong-Chi-Man ( Montpellier)
Pr S. Jugé, Université de Dijon
Dr J. Maddaluno (Rouen)
Pr P.-Y. Renard (Rouen)
Pr C. Afonso (Rouen)
Pr V. Dalla (Le Havre)