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Ecole Doctorale de Chimie Moléculaire de Paris Centre - ED 406 - Director: Prof. Anna Proust !
Program of the 16th Conference of the Doctoral School
Amphitheatre Herpin
Monday, May 23, 2016 morning sessions
Moderator
8h45 – 9h00 Opening of the 16th conference by Prof. A. Proust
9h00 – 10h00
Prof. Michel Etienne Distorsions CC agostiques et le ligand cyclopropyle : expérience, théorie, réactivité
10h00 – 10h15 Laura Ferrand Cationic niobium as a new catalytic system for hydro-functionalization of C‒C multiple bonds
Prof. Anna Proust
10h15 – 10h30 Maxime Laugeois Synergistic Pd(0)/amine catalysis: a powerful tool for the asymmetric formal [3+2] cycloaddition of vinyl cyclopropanes with enals
10h30 – 11h00 Coffee break
11h00 – 11h15 Morgan Languet Rhodium(III) catalyzed C−H activation of heterocycles under mild conditions
11h15 – 11h30 Fabrizio Medici New silicon derived frustrated Lewis pairs
11h30 – 11h45 Christophe Lévêque Development of a versatile approach for the generation of alkyl radicals by photooxidation of alkylsilicates
Dr. Maxime Vitale
11h45 – 12h00 Fei Ye Solvent-free ruthenium trichloride-mediated [2 + 2 + 2] Cycloaddition: an efficient access toward fluorenone derivatives
12h00 – 14h00 Lunch
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Monday, May 23, 2016 afternoon sessions
Moderator
14h00 – 14h15 Radhouan Maazaoui Domino methylenation–hydrogenation of aldehydes and ketones by combining Matsubara reagents and Wilkinson’s catalyst
14h15 – 14h30 Liang Chang Methyl coumalate involved Morita-Baylis-Hillman reaction
14h30 – 14h45 Alexandra Feraldi Ring contraction: synthesis of functionalized α-(trifluoromethyl)-pyrrolidines and piperidines
Dr. Marion Barbazanges
14h45 – 15h00 Thomas Aubineau Formation of N-containing heterocycles
15h00 – 15h30 Coffee break
15h30– 15h45 Ludovic Leleu Kojic acid : a natural compound for organic synthesis and access to biologically active molecules
15h45 – 16h00 Benjamin Flamme Rational design of 5V organic electrolytes
16h00 – 16h15 François-Xavier Guillon Electrochemical microRNA biosensors: an ergonomic miniaturized two-electrode setup
Dr. Cyril Ollivier
16h15 – 16h30 Xia Wang Photocatalytic CO2 reduction by multinuclear metal complexes
16h30 – 17h30 Prof. Marc Robert Molecular catalysis of the reduction of CO2 with iron porphyrins. From mechanistic studies to optimization of catalysts and to efficient electrolizers for CO2 splitting into CO and O2
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Tuesday, May 24, 2016 morning sessions
Moderator
8h45 – 9h45 Prof. William B. Motherwell The measurement of noncovalent functional group interactions with π clouds using designed molecular balances.
9h45 – 10h00
Pascal Matton Glycolipid functionalized microdroplets for cells vectorization
10h00 – 10h15 Thomas Denèfle TSP-1 mimetic peptides inducing selective apoptosis of cancer cell lines: design, synthesis and structure-activity relationship studies
Prof. Matthieu Sollogoub
10h15 – 10h30 Sébastien Cardon Quantification of the internalization efficacy of homeoproteins and derived-cell penetrating domains
10h30 – 11h00 Coffee break
11h00 – 11h15 Thomas Driant On the influence of the protonation states of active site residues on AChE reactivation: a QM/MM approach
11h15 – 11h30 Mathilde Belnou Modulation of the calmodulin binding domain of the protein FKBP52
11h30 – 11h45 Caroline Thebault Ultra-magnetic liposomes and their in vivo guidance monitoring by MRI for cancer therapy
Dr. Sébastien Blanchard
11h45 – 12h00 Frédéric Thiebaut Identification of rare DNA base protein partner using photolabeling and mass spectrometry
12h00 – 14h00 Lunch
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Tuesday, May 24, 2016 afternoon sessions
Moderator
14h00 – 14h15 Ourania Makrygenni Hybrid polyoxometalates for homogeneous supported catalysis
14h15 – 14h30 Juan Ramón Jiménez-Gallego Switchable redox active Fe/Co cyanide molecular cube encapsulating K+ or Cs+
14h30 – 14h45 Emilie Mathieu Antioxidant manganese complexes: Investigation of their activity and sub-cellular location.
Dr. Guillaume Vives
14h45 – 15h00 Emmanuel Puig Novel class of Pt(II) metallocages : design and self-assembly
15h00 – 15h30 Coffee break
15h30 – 15h45 Florence Hiault Synthesis of α-amino β-hydroxy acids Biocatalytic aldolization and kinetic resolution of 1,2-diols
15h45 – 16h00 Laurine Gonnard Metal-catalyzed arylation of piperidines
16h00 – 16h15 Caleb Medena Helicenes: synthesis and application in catalysis
Prof. Giovanni Poli
16h15 – 17h15 Prof. Maurizio Prato Novel Functional Materials from Nanocarbons to Perylene Bisimides
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Journées)de)Chimie)Moléculaire)2016! Michel!ETIENNE!
Distorsions!CC!agostiques!et!le!ligand!cyclopropyle!:!expérience,!théorie,!réactivité!!
michel.etienne@lcc,toulouse.fr!!
Laboratoire)de)Chimie)de)Coordination)du)CNRS)et)Université)Toulouse)III)–)Paul)Sabatier,)205)route)de)Narbonne,)
BP)99044,)31077)Toulouse)Cedex)4.)
!
!!
Alors! que! les! nombreuses! observations,! la! nature,! les! causes! et! les! conséquences! des! distorsions! CH!agostiques!–!formellement!interactions!à!3!centres!et!2!électrons!(3c,2e)!entre!une!liaison!CH!d’un!ligand!et!un!métal!M!–!sont!connues!toujours!plus!en!détail,!de!telles!manifestations!pour!d’autres!liaisons!saturées!CX,! en! particulier! CC,! sont! beaucoup! plus! rares.1! Ceci! est! au! moins! vrai! pour! des! raisons! stériques! et!statistiques!mais!revêt!une!importance!certaine!dans!le!cadre!très!actuel!d’études!sur!l’activation!de!liaisons!fortes!et!inertes.!! Il! y! a!quelques!années,!on!a!découvert!dans! l’équipe!une! famille!de! complexes!de!niobium!dans!lesquels!un!ligand!cyclopropyle!c,C3H5!présentait!de!telles!distorsions!CC!agostiques.!Les!complexes!iso,!et!n,propyle!présentent!plus!classiquement!des!distorsions!CH!agostiques.!A!la!recherche!d’autres!exemples!de!ces!manifestations,!je!présenterai!une!excursion!dans!la!chimie!des!métaux!des!groupes!5!à!1!avec!le!ligand!cyclopropyle! aussi! bien! du! point! de! vue! structural! que! de! la! réactivité! (activation! de! liaisons! CH!d’hydrocarbures,!méthane! en! particulier).! A! la! lumière! de! certains! outils! de! la! chimie! computationnelle,!j’ajouterai! une! réflexion! sur! la!description!et! la!nature!de! ces!distorsions!qui! varient! selon! la!nature!des!métaux!et!des!complexes.!
!!
!!! !
1 “Intramolecular C–C Agostic Complexes: C–C Sigma Interactions by Another Name”. M. Etienne, A. S. Weller, Chem. Soc. Rev. 2014, 43, 242-259.
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Journées)de)Chimie)Moléculaire)2016! Marc!Robert!
Molecular!catalysis!of!the!reduction!of!CO2!with!iron!porphyrins.!!From!mechanistic!studies!to!optimization!of!catalysts!!
and!to!efficient!electrolizers!for!CO2!splitting!into!CO!and!O2!
robert@univ,paris,diderot.fr!
Université)Paris)Diderot,)Sorbonne)Paris)Cité,)Laboratoire)Electrochimie)Moléculaire,)UMR)CNRS)7591,))
15)rue)Jean)de)Baïf,)75013)Paris,)France)
!
!!
Recent!attention!aroused!by!the!reduction!of!carbon!dioxide!has!as!main!objective!the!production!of!useful!products!−!the!“solar!fuels”!−!in!which!solar!energy!would!be!stored.!One!route!to!this!goal!consists!in!first!converting!sunlight!energy!into!electricity!than!could!be!further!used!to!reduce!CO2!electrochemically.!Conversion!of!carbon!dioxide!into!carbon!monoxide!is!a!key,step!through!the!classical!dihydrogen,reductive!Fischer,Tropsch!chemistry.!We!will!describe!our!work!in!this!field!using!various! iron!tetraphenylporphyrin!derivatives,!that!prove!to!be!remarkable!catalysts!of!the!reduction!of!CO2!to!CO!when!reduced!at!the!Fe(0)!oxidation! state,! both! in! terms! of! selectivity,! durability,! overpotential! and! turnover! frequency.! 1,2,3,4,5,6!Understanding!the!molecular!mechanisms!for!catalysis!allows!identifying!the!main!factors!that!control!the!process!and!optimizing!the!catalyst!structure.!7!
!Extending! these! studies,! we! recently! discovered! that! it! was! possible,! with! a! water,soluble! Fe!
porphyrin,!to!catalyze!the!electrochemical!conversion!of!carbon!dioxide!into!carbon!monoxide!in!pure!water!8!as!well!as!to!transfer!catalytic!activity!to!solid!surfaces!by!grafting!of!the!molecular!catalysts.9!Finally,!and!based!on!these!advances,!we!very!recently!designed!an!efficient!electrolyzer!for!CO2!splitting!in!neutral!water!using!only!earth!abundant!materials.10!!
Acknowledgments:!ANR,!SATT!IDF!Innov!as!well!as!Labex!MiChem!are!gratefully!acknowledged!for!funding.!! !
1 S. Drouet, C. Costentin, M. Robert, J-M. Savéant, Science, 2012, 338, 90. 2 C. Costentin, M. Robert, J-M. Savéant, Chem. Soc. Rev., 2013, 42, 2423. 3 C. Costentin, G. Passard, M. Robert, J-M. Savéant, (a) J. Am. Chem. Soc., 2013, 135, 9023.(b) J. Am. Chem. Soc., 2014,
136, 11821. 4 C. Costentin, M. Robert, J-M. Savéant, Acc. Chem. Res., 2015, 48, 2996. 5 C. Costentin, G. Passard, M. Robert, J-M. Savéant, PNAS, 2014, 111, 14990. 6 J. Bonin, M. Robert, M. Routier, J. Am. Chem. Soc., 2014, 136, 16768. 7 M. Robert et al., submitted. 8 C. Costentin, M. Robert, J-M. Savéant, A. Tatin, PNAS, 2015, 112, 6882. 9 A. Maurin, M. Robert, J. Am. Chem. Soc., 2016, 138, 2492. 10 M. Robert et al., PNAS, 2016, in press.
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Journées)de)Chimie)Moléculaire)2016! William!Motherwell,!FRS,!FRSE.!!
The!Measurement!of!Noncovalent!Functional!Group!Interactions!with!π!Clouds!using!designed!Molecular!Balances.!
[email protected] !
!Christopher)Ingold)Laboratory,)Department)of)Chemistry,)University)College)London,)20,)Gordon)St.,)London,)
WC1HOAJ.))UK.)
!
!!
Noncovalent! interactions!are!now!firmly!established!as!vital! control!elements! for!chemical!and!biological!recognition,! and!detailed!quantitative! knowledge!of! these! very!weak! forces! is! now! therefore! considered!essential! for! the! rational!design!of!organocatalysts,!new!drugs!and! supramolecular!materials.!Our! recent!progress!in!this!area!using!a!unique!top!pan!molecular!balance!based!on!the!dibenzobicyclo[3.2.2]nonane!molecular!framework!and!related!congeners!will!be!discussed.!!!!
!!!
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!
For a leading reference see: I. Pavlakos, T. Arif, A.E. Aliev, W.B. Motherwell, G.J. Tizzard, and S. J. Coles, Angew. Chem. Int. Ed. 2015, 54, 8169. ! !
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Journées)de)Chimie)Moléculaire)2016! Maurizio!Prato!!
Novel!Functional!Materials!from!Nanocarbons!to!Perylene!Bisimides!
[email protected] !
!Dipartimento)di)Scienze)Chimiche)e)Farmaceutiche,)Università)degli)Studi)di)Trieste,)Piazzale)Europa)1,)34127)Trieste,)
Italy)and)CIC)BiomaGUNE,)San)Sebastian,)Spain)
!
!!
We! will! show! how! nanocarbons! are! particularly! suited! for! a! variety! of! applications,! ranging! from!neurosciences!to!energy.! In!particular,!we!will!discuss!how!with!carbon!nanotubes!are! ideal!materials! for!integration!with!neuronal!tissues.!Nanotubes!are!compatible!with!neurons,!but!especially!they!play!a!very!interesting! role! in! interneuron! communication,! opening! possibilities! towards! applications! in! spinal! cord!repair!therapy.!In!addition,!in!combination!with!catalysts!of!different!nature,!carbon!nanotube!modified!surfaces!can!serve!for!many! scopes.! Experiments! aiming! at! the! splitting! of!water! to! give! oxygen,! and! therefore,!molecular!hydrogen,!ideal!for!clean!energy!generation,!will!be!described.!Finally,!moving! from!electrochemical! devices! to! light,driven! processes,!we!will! discuss! the! synthesis! and!applications!of!perylene!bisimides,!which,!in!combination!with!polyoxometalates,!are!ideal!partners!in!the!photosplitting!of!water.!!! !
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!Journées)de)Chimie)Moléculaire)2016! Laura!FERRAND!!
Cationic!niobium!as!a!new!catalytic!system!for!hydroRfunctionalization!of!C‒C!
[email protected] !
PhD!advisors:!Dr!Muriel!Amatore,!Dr!Corinne!Aubert!Institut)Parisien)de)Chimie)Moléculaire))
Université)Pierre)&)Marie)Curie)
)4,)place)Jussieu)75252)PARIS)Cedex)05)
!Located!between!vanadium!and!tantalum!in!the!periodic!table,!niobium!is!known!for!its!large!applications!notably! in! the! fields!of! steel! and!aeronautical! industries!and! in!medicine!as!well.!Niobium!has!also!been!widely!studied!in!the!field!of!inorganic!chemistry,!with!the!synthesis!of!a!large!number!of!niobium!complexes.!However,!this!element!is!definitely!much!less!known!in!organic!chemistry.!1!!The!most!common!niobium!complex!is!the!commercially!available!NbCl5!and!it!has!been!used,!either! in!a!stoichiometric!or!in!a!catalytic!amount,!as!a!Lewis!acid!in!different!organic!reactions!such!as!Aldol!reactions!and!Diels,Alder!reactions.!!As!for!many!other!chlorinated!metals,! it!has!been!demonstrated!that! it!was!possible!to!generate!cationic!niobium(V)!from!NbCl5,!and!thus!to!change!the!properties!of!the!complex.!However,!this!methodology!has!only!been!applied!once!for!Friedel,Crafts!acylation!and!Sakurai,Hosomi!reaction!of!acetals.!2!!In!this!context!and!with!the!aim!to!get!more!insight!into!the!reactivity!of!cationic!niobium(V),!we!envisaged!!to!explore!the!behavior!of!this!catalytic!system!for! intramolecular!hydro,functionalization!of!C‒C!multiple!bonds.!Indeed!this!reaction!is!well!known!to!be!a!powerful!strategy!for!the!construction!of!important!building!blocks!in!organic!synthesis,!and!it!has!been!widely!studied!over!the!past!ten!years.!3!!It! was! found! that!mixtures! of! NbCl5! and! AgX! salts! displayed! an! efficient! catalytic! activity! for! the! hydro,functionalization!of! alkenes,! leading! to! the! straightforward! formation!of! a!wide! range!of!heterocycles.!A!survey!of!the!preliminary!substrate!scope!will!be!presented.!!
!!
Access)to)tetrahydrofuran,)tetrahydropyran,)pyrrolidine,)lactam,)lactone…)
!
!
Aknowledgment:!We!wish!to!acknowledge!the!Ministère!de!l’Enseignement!Supérieur!et!de!la!Recherche.!!! !
1 Jr. V. Lacerda, D. A. dos Santos, L. Carlos da Silva-Filho, S. J. Greco, R. B. dos Santos, Aldrichim. Acta 2012, 45,
19‒26 ; Y. Obora, Eur. J. Org. Chem. 2015, 5041‒5054. 2 S. Arai, Y. Sudo, A. Nishida, Tetrahedron 2005, 61, 4639‒4642. 3 N. T. Patil, R. D. Kavthe, V. S. Shinde, Tetrahedron 2012, 68, 8079‒8146.
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Journées)de)Chimie)Moléculaire)2016! Maxime!LAUGEOIS!!
Synergistic!Pd(0)/amine!catalysis!:!a!powerful!tool!for!the!asymmetric!formal![3+2]!
cycloaddition!of!vinyl!cyclopropanes!with!enals!maxime.laugeois@chimie,paristech.fr!
PhD!advisors!:!Dr.!Virginie!Ratovelomanana,Vidal,!Dr.!Véronique!Michelet!and!Dr.!Maxime!Vitale!PSL)Research)University,)Chimie)ParisTech)–)CNRS,)Institut)de)Recherche)de)Chimie)Paris,)Paris,)75005)
!!
The! stereoselective! construction! of! the! carbocyclic! core! of! cyclopentane! derivatives! through! an!asymmetric![3+2]!cycloaddition!process!is!undeniably!one!of!the!most!efficient!and!straightforward!synthetic!method!available.1!
In!1985,!Tsuji!et)al.!established!that,!under!palladium(0)!catalysis,!vinylcyclopropanes!(VCPs)!bearing!electron!withdrawing!groups!could!undergo![3+2]!cycloaddition!reactions!with!electron,poor!olefins!via)the!formation! of! transient! zwitterionic! π,allyl! palladium! intermediates.2! Since! then,!much! efforts! have! been!dedicated!to!the!development!of!enantioselective!versions!of!this!cyclopentannulation!process,!essentially!based!on!the!use!of!highly!activated!acceptors!and!a!Pd(0)/chiral!ligand!strategy.3!
!Aware!of!these!limitations,!we!envisioned!an!alternative!catalytic!strategy!in!which!iminium/enamine!
organocatalysis!and!palladium(0)!catalysis!would!be!merged.4!As!direct!benefit!of!this!original!approach,!the!synergy!operating!between! the! chiral! secondary! amine! and! the!palladium! complex!permitted! to! employ!simple!enals!and!to!control!the!stereoselectivity!with!a!readily!available!source!of!chirality.!
This!new!synthetic!method!provided!access!to!a!wide!range!of!optically!active!cyclopentane!scaffolds!in!good!yields!and!diastereoselectivities!and!excellent!enantiomeric!excesses.51!
!
Aknowledgment:!MESR!! !
1 N. Iwasawa, in Comprehensive Organic Synthesis II, ed. P. Knochel and G. A. Molander, Elsevier, 2014, vol. 5, pp.
273-350. 2 I. Shimizu, Y. Ohashi and J. Tsuji, Tetrahedron Lett., 1985, 26, 3825-3828. 3 (a) B. M. Trost and P. J. Morris, Angew. Chem. Int. Ed., 2011, 50, 6167-6170; (b) L. Mei, Y. Wei, Q. Xu and M. Shi,
Organometallics, 2012, 31, 7591-7599; (c) F. Wei, C.-L. Ren, D. Wang and L. Liu, Chem. Eur. J., 2015, 21, 2335-2338; (d) M.-S. Xie, Y. Wang, J.-P. Li, C. Du, Y.-Y. Zhang, E.-J. Hao, Y.-M. Zhang, G.-R. Qu and H.-M. Guo, Chem. Commun., 2015, 51, 12451-12454; (e) Z.-S. Liu, W. Li, T. Kang, L. He and Q. Liu, Org. Lett., 2015, 17, 150-153.
4 For a recent review, see: S. M. Inamdar, V. S. Shinde and N. T. Patil, Org. Biomol. Chem., 2015, 13, 8116-8162. 5 M. Laugeois, S. Ponra, V. Ratovelomanana-Vidal, V. Michelet and M. R. Vitale, Chem. Commun., 2016, 52, 5332-
5335.
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Journées)de)Chimie)Moléculaire)2016! Morgan!LANGUET!!
Rhodium(III)!catalyzed!C−H!activation!of!heterocycles!under!mild!conditions!
[email protected] !PhD!advisors:!Pr.!Janine!Cossy!&!Dr.!Stellios!Arseniyadis!
Laboratoire)de)Chimie)Organique,)ESPCI)Paris)Tech,)10)rue)Vauquelin)75231)PARIS)CEDEX)5)
!!
Five!membered!heterocycles! represent! an! important! class!of!molecules!which! are! found! in! a!number!of!natural!products!as!well! as! various!pharmaceuticals!and!agrochemicals.1!As! such,! the! synthesis!of!highly!functionalized!heterocycles!remains!still!today!a!great!challenge!still!today!in!organic!chemistry.!!During!the!past!two!decades,!C−H!activation!has!appeared!as!a!robust!and!highly!straightforward!method!to!access!diversely!substituted!heterocycles,2!particularly!with!Rhodium!catalysts.3!However,!to!the!best!of!our!knowledge,!there!are!only!a!few!examples!of!C−H!activation!processes!involving!cyclic! dienol! carbamates! reported! in! the! literature.4! Based! on! this! observation,! a! cationic! Rhodium(III),catalyzed!C−H!olefination!has!been!developed!offering!high!levels!of!regioselectivity!with!a!wide!range!of!substituted!heterocycles,!thus!enabling!the!efficient!introduction!of!an!acrylate!moiety!under!mild!conditions!and!with!a!low!catalyst!loading!(Scheme!1).!!
Scheme!1.!
!We! will! present! and! discuss! the! scope! and! limitations! of! this! method! as! well! as! various! post,functionalizations.! !
1 (a) B. A. Keay, J. M. Hopkins, P. W. Dibble in Comprehensive Heterocyclic Chemistry III, Vol. 3 (Eds.: G. Jones, C. A.
Ramsden), Elsevier, Amsterdam, 2008, 571-623. (b) Lipshutz, B. H. Chem. Rev. 1986, 86, 795. 2 For recent reviews on C−H activation, see: (a) Engle, K. M.; Mei, T.-S.; Wasa, M.; Yu, J.-Q. Acc. Chem. Res. 2012, 45,
788. (b) Leow, D.; Li, G.; Mei, T.-S.; Yu, J.-Q. Nature 2012, 486, 518. (c) Ackermann, L. Chem. Rev. 2011, 111, 1315. (d) Song, G.; Wang, F.; Li, X. Chem. Soc. Rev. 2012, 41, 3651. (e) Patureau, F. W.; Wencel-Delord, J. Glorius, F. Aldrichimica Acta 2012, 45, 31.
3 (a) Boultadakis-Arapinis, M.; N. Hopkins, M.; Glorius, F. Org. Lett. 2014, 16, 1630. (b) Gong, T.-J.; Xiao, B.; Liu, Z.-J.; Wan, J.; Xu, J.; Luo, D.-F.; Fu, Y.; Liu, L. Org. Lett. 2011, 13, 3235. (c). D. Otley, K.; A. Ellman, J. Org. Lett. 2015, 17, 1332. (d) Lu, Y.; Wang, H.-W.; E. Spangler, J.; Chen, K.; Cui, P.-P.; Zhao, Y.; Sun, W.-Y.; Yu, J.-Q. Chem. Sci. 2015, 6, 1923. (e) Feng, C.; Loh, T.-P. Chem. Commun. 2011, 47, 10458.
4 Schröder, N.; Lied, F.; Glorius, F. J. Am. Chem. Soc. 2015, 137, 1448.
X
O DGRh
R
H X
O DG
Radditive, solvent, T
25 examplesup to 93% yieldGram-ScaleMild conditions
X
O
R
X
H
R
X
Ar
R
(X = O, N, S)
C−O bondcleavage
Removal
Directing Group
Cross-coupling
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Journées)de)Chimie)Moléculaire)2016! Fabrizio!MEDICI!!
New!Silicon!Derived!Frustrated!Lewis!Pairs!
[email protected] !!PhD!advisor:!Pr.!Louis!Fensterbank
Laboratory!Institut)Parisien)de)Chimie)Moleculaire,)UMR)CNRS)8232)Sorbonne Universités UPMC-Paris06, 4 Place Jussieu, 75252 Paris
!!
A!Frustrated!Lewis!Pair!(FLP)!is!a!partially!formed!Lewis!Acid,Base!adduct!in!which!the!properties!of!the!two!centres!are!unquenched1.!This!means!that!the!adduct!still!features!an!electrophilic!centre!and!a!nucleophilic!centre!active! in!close!proximity.!As!now!well! illustrated! in!the! literature! it! is!possible!to!use!FLPs’! for!the!activation!of!small!molecules,!like!H2
2!and!CO23.!
My!thesis!work!focuses!on!the!study!of!the!possible!application!of!the!Martin!spirosilane4!as!a!Lewis!acid!in!the!formation!of!new!FLPs.!This!particular!spirosilane!was!chosen!because!of!its!high!Lewis!acidity!and!of!the!ability!of!silicon!to!become!hypervalent5.!The!chosen!Lewis!bases!as!partners!of!the!Martin!spirosilane!are!NHC!carbenes6!due!to!their!high!nucleophilicity!and!steric!hindrance.!Our!findings!along!these!lines!will!be!presented.!!!!!
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1 Jenny S. J. McCahill, Gregory C. Welch, and Douglas W. Stephan, Angew. Chem. Int. Ed., 2007, 46, 4968-4971 2 Douglas W. Stephan, Org. Biomol. Chem., 2012, 10, 5740-5746 3 X. Zhao, Douglas W. Stephan, Chem. Commun., 2011, 47, 1833-1835 4 Edmund F. Perozzi, J. C. Martin, J. Am. Chem. Soc, 1979, 101, 1591-1953 5 Robert J. P. Corriu, Journal of Organometallic Chemistry, 1990, 400, 81-106!6 Anthony J. Arduengo III, Michael Kline, Joseph C. Calabrese, F. Davidson, J. Am. Chem. Soc., 1991, 113, 9704-9705!
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Journées)de)Chimie)Moléculaire)2016! Christophe!Lévêque!!
Development!of!a!versatile!approach!for!the!generation!of!alkyl!radicals!by!
photooxidation!of!alkylsilicates!
e,mail!address:!cleveque@ens,cachan.fr!PhD!advisor(s):!Louis!FENSTERBANK!and!Cyril!OLLIVIER.!
Laboratory:)Institut)Parisien)de)Chimie)Moléculaire,)Equipe)MACO)
)Université)Pierre)et)Marie)Curie)Sorbonne)Universités)
4)Place)Jussieu,)Bât)F)2eme)ét.)case)229,)75252)Paris)cedex)5)
!Visible,light!photoredox!catalysis!has!emerged!as!a!very!powerful!strategy!to!generate!radical!species!
swiping! all! the! tin,mediated! or! some! stoichiometric! redox!methodologies1.!Many! opportunities! are! now!available! to! access! a! large! range! of! C,centered! radicals,! based! either! on! photooxidative! or! reductive!processes.2!However,!generation!of!unstabilized!alkyl!radicals!is!still!a!challenge.!Methodologies!have!been!developed! to! generate! stabilized! alkyl! radicals! by! photooxidation! of! organotrifluoroborates3! or! α,aminocarboxylates.4!Recently,!our!group!first!reported!the!generation!of!unstabilized!alkyl!primary!radicals!by!photooxidation!of!bis(catecholato),alkylsilicates.5!These!radicals!can!be!trapped!by!radical!acceptors!or!engaged!with!(hetero)aryl!halides!or!alkenyl!halides!as!electrophiles!in!dual!photoredox/nickel!catalysis!for!the!formation!of!C(sp3),C(sp2)!bonds.6!Usually,!metal!complexes!based!on!ruthenium!or!iridium!are!used!as!photocatalysts! but! increasing! efforts! have! been! realized! to! develop! processes! involving! organic!photocatalysts.7!
Scheme 2 Photooxidation of bis(catecholato)-akylsilicates: toward C-C bond formation.
Acknowledgment:!Ministère!de!l’Enseignement!Supérieure!et!de!la!Recheche,!ENS!Cachan.!! !
1 (a) P. Renaud, M. P. Sibi in Radicals in Organic Synthesis, 2001, vol 1& 2, Wiley-VCH, Weinheim. (b) D. P. Curran, N. A. Porter, B. Giese in Stereochemistry of Radical Reactions, 1996, Wiley-VCH, Weinheim. 2 C. K. Prier, D. A. Rankic, D. W. C. MacMillan Chem. Rev. 2013, 113, 5322−5363. 3 Y. Yasu, T. Koike, M. Akita Adv. Synth. Catal. 2012, 354, 3414–3420. 4 Z. Zuo, D. W. C. MacMillan J.Am.Chem.Soc. 2014, 136, 5257−5260. 5 V. Corcé, L.-M. Chamoreau, E. Derat, J.-P. Goddard, C. Ollivier, L. Fensterbank Angew.Chem. Int.Ed. 2015, 54, 11414 –11418. 6 C. Lévêque, L. Chenneberg, V. Corcé, J.-P. Goddard, C. Ollivier, L. Fensterbank Org. Chem. Front. 2016, 3, 462-465. 7 D. A. Nicewicz, T. M. Nguyen ACSCatal, 2014, 4, 355−360.
Page 14
Journées)de)Chimie)Moléculaire)2016! Fei!YE!!
SolventRFree!Ruthenium!TrichlorideRMediated![2!+!2!+!2]!Cycloaddition:!!
An!Efficient!Access!Toward!Fluorenone!Derivatives!!
fei.ye@chimie,paristech.fr!!PhD!advisors:!Mansour!Haddad,!Véronique!Michelet!and!Virginie!Vidal!!
Laboratory:)Institut)de)Recherche)de)Chimie)Paris)(UMR)8247),)équipe)Catalyse,)Synthèse)de)Biomolécules)et)
Développement)Durable)(CSB2D)fChimie)ParisTech,)11)rue)Pierre)et)Marie)Curie,)75005)Paris,)France))
!Fluorenones!derivatives1!are!found!in!many!natural!and!pharmaceutical!products.2!These!compounds!have!also!been!used!as!intermediates!in!material!science.3!Transition,metal,catalyzed![2+2+2]!cycloadditions!have!been! recognized!as!one!of! the!most!powerful! atom,economical!method! to! access! carbo,!or!heterocyclic!aromatic! compounds.4! To! the! best! of! our! knowledge,! only! a! single! report! describes! the! use! of! [2+2+2]!cycloaddition!reactions!to!access!such!scaffolds.5!As!a!continuation!of!our!research!program!to!explore!the!metal,catalyzed![2+2+2]!cycloadditions!under!solvent,free!conditions,6!we!present!here!a!novel!and!general!route!for!the!preparation!of!highly!substituted!fluorenones!via!RuCl3rnH2O,promoted![2+2+2]!cycloaddition!of!substituted!carbonyl!bridged!diynes!with!substituted!internal!alkynes.7!
!!
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Acknowledgment:!F.!Y.!thanks!the!China!Scholarship!Council!(CSC).! ! !
1. For recent publications, see: H. Li, R. Zhu, W. Shi, K. He, Z. Shi, Org. Lett., 2012, 14, 4850; Z. Shi and F. Glorius, Chem. Sci.,
2013, 4, 829; J. K. Laha, K. P. Jethava and S. Patel, Org. Lett., 2015, 17, 5890; D. R. Kumar and G. Satyanarayana, Org. Lett., 2015, 17, 5894; J. Song, F. Wei, Wei Sun, Ke Li, Y. Tian, C. Liu, Y.Li, and L.Xie, Org. Lett. 2015, 17, 2106 and references cited therein.
2. M. L. Greenlee, J. B. Laub, G. P. Rouen, F. Dininno, M. L. Hammond, J. L. Huber, J. G. Sundelof and G. G. Hammond, Bioorg. Med. Chem. Lett. 1999, 9, 3225; P. J. Perry, M. A. Read, R. T. Davies, S. M. Gowan, A. P. Reszka, A. A. Wood, L. R. Kelland and S. Neidle, J. Med. Chem., 1999, 42, 2679; M. T. Tierney and M. W. Grinstaff, J. Org. Chem., 2000, 65, 5355.
3. Q. Liu, W. Yao, Y. Shi and J. Tang, Heterocycles 2012, 85, 1077. A. Leliege, C. L. Regent, M. Allain, P. Blanchard and J. Roncali, Chem. Commun. 2012, 48, 8907.
4. S. Saito, Y. Yamamoto, Chem. Rev. 2000, 100, 2901; V. Gandon, C. Aubert, M. Malacria, Chem. Commun. 2006, 21, 2209; D. M. D’Souza, T. J. J. Muller, Chem. Soc. Rev. 2007, 36, 1095; N. Weding, M. Hapke, Chem. Soc. Rev. 2011, 40, 4525; G. Domingez, J. Pérez-Castells, Chem. Soc. Rev. 2011, 40, 3430; Y. Shibata, K. Tanaka, Synthesis 2012, 44, 323; Y. Yamamoto, Heterocycles 2013, 87, 2459; F. R. Truscott, G. Maestri, R. Rodriguez, M. Malacria, in: Modern Alkyne Chemistry, (Eds.: B. M. Trost, C.-J. Li), Wiley-VCH, Weinheim, 2014, 143; G. Domingez, J. Pérez-Castells, in: Comprehensive Organic Synthesis, 2nd edn., (Eds.: P. Knochel,G. A, Molander), Elsevier, Amsterdam, 2014, 5, 1537; M. Amatore, C. Aubert, Eur. J. Org. Chem. 2015, 265.
5. R. P. Kaiser, F. Hessler, J. Mosinger, I. Císařová and M. Kotora, Chem. Eur. J., 2015, 21, 13577. 6. J. Jacquet, A.-L. Auvinet, A. K. Mandadapu, M. Haddad, V. Ratovelomanana-Vidal and V. Michelet, Adv. Synth. Catal. 2015, 357,
1387. 7. Manuscript in preparation.!
! AtomReconomical!process!! CostReffective!ruthenium!catalyst!! Nontoxic!solventRfree!conditions!! Ligand!and!additive!free!system!!! Access!to!aromatic!and!heterocyclic!fluorenones!! Wide!range!of!functional!groups!tolerated!! Gram!scale!synthesis!
O
R1
R2
R3
R3R2
R1O
R3
R3
RuCl3 · nH2O 5 mol%no solvent
50 to 80 °C, 2-18 h(2 eq.) 18 examples
up to 81% yield
Page 15
Journées)de)Chimie)Moléculaire)2016! Radhouan!MAAZAOUI!!
Domino!Methylenation–Hydrogenation!of!Aldehydes!and!ketones!by!Combining!
Matsubara!Reagents!and!Wilkinson’s!Catalyst!!
[email protected] !!PhD!advisor(s):!Pr.!Fabrice!Chemla,!Dr.!Olivier!JACKOWSKI!!
!Development!of!new!synthetic!processes!that!meet!both!economic!and!environmental!needs!is!one!of!the!major!challenges!in!organic!chemistry!and!its!main!source!of!innovation.!Finding!new!strategies!that!reduce!the!number!of!elementary!operations!required!to!achieve!a!given!transformation!participates!to!this!effort!since! it!allows!significant!waste!diminution.1!Thus,! in! this! context,!one,pot!multiple! transformations!have!attracted! an! ever,increasing! interest.2,3! Carbonyl! methylenation! is! an! important! method! for! C–C! bond!formation!because!the!resulting!alkene!offers!a!valuable!handle!for!further!elaboration.!However,!processes!wherein! the! generated! alkene! undergoes! a! subsequent! transformation! in! the! same! reaction!media! are!scarce.4!!A!case!to!the!point! is! the!combination!of!aldehyde!methylenation!and!hydrogenation.!This!sequence! is!a!common!strategy!to!introduce!an!ethyl!group!from!aldehydes!in!multi,step!synthesis!of!natural!products,5!bioactive! analogues6! or! key! intermediates.7! In! this! context,! the! combination! of! Matsubara’s! reagents![CH2(ZnI)2]! and! Wilkinson’s! complex! allows! the! domino! methylenation–hydrogenation! of! aromatic! and!aliphatic!aldehydes!and!ketones!in!good!yields.!The!scope!and!limitation!of!this!process!will!be!discussed.!!
H"or"R'R
OR="Alkyl"or"Aryl
IZn ZnI , ClRh(PPh3)3
H2"atmosphere
Domino&Process
H"or"R'R
up"to"86% !!
!1! "(a)"Sheldon,"R."A."Green%Chem.,"2007,"9,"1273."(b)"Constable,"D."J."C.;"Dunn,"P."J.;"Hayler,"J."D.;"Humphrey,"G."R.;"Leazer,"J."L."Jr.;"Linderman,"R."J.;"
Lorenz,"K.;"Manley,"J.;"Pearlman,"B."A.;"Wells,"A.;"Zaks,"A.;"Zhang,"T."Y.""Green%Chem.2007,"9,"411."2! (a) Anastas, P. T.; Kirchhoff, M. M. Acc. Chem. Res. 2002, 35, 686. (b) Anastas, P. T.; Warner, J. C. Green chemistry
theory and practice, Oxford, Oxford University press, 1998, pp135. 3! For a seminal review on domino reactions, see: (a) Tietze, L. F. Chem. Rev., 1996, 96, 115; (b) Tietze, L. F.; G.
Brasche, G.; Gericke, K. M. in Domino Reactions in Organic Synthesis, Wiley-VCH,Weinheim, 2006. (c) Borukhova, S.; Tietze, L. F. Green Processing and Synthesis 2014, 3, 501.
4! (a) Kawasaki, T.; Ogawa, A.; Terashima,R. Saheki, T.; Ban, N.; Sekiguchi,H; . Sakaguchi, K; Sakamoto,M. J. Org. Chem.2005, 70, 2957; (b) Kawasaki, T.;Shinada, M.;Kamimura, D.; Ohzono, M.; Ogawa, A. Chem. Commun.2006, 4, 420; (c) Breit, B.; Zahn, S; K. Angew. Chem. Int Ed. 1999, 38, 969; (d) Breit, B.; Zahn, S. K. Tetrahedron2005, 61, 6171; (e) Farwick, A.; Helmchen, G. Adv. Synth. Catal. 2010, 352, 1023; (f) Prasad Mishra, G.; Venkata Ramana, G.; Venkateswara Rao, B. Chem. Commun. 2008, 3423.
5! Mizoguchi, H.; Oikawa, H.; Oguri, H. Nature Chem.2014, 6, 57. 6! Rhoden, J. B.; Bouvet, M.; Izenwasser, S.; Wade, D.; Lomenzo, S. A.; Trudell, M. L. Biorg. Med. Chem.2005, 13,
5623. 7! Yamane, T.; Izhizaki, M.; Suzuki, M.; Takahashi, M.; Hiroya, K.; Takano, S.; Ogasawara, K. Heterocycles1996, 42,
65. ! !
Sorbonne!Universités,!UPMC!Univ!Paris!06,!CNRS!UMR!8232,!Institut!Parisien!de!Chimie!Moléculaire!(IPCM),!CC!229,!4!place!Jussieu,!F,75252!Paris!Cedex!05,!France.!
Page 16
Journées)de)Chimie)Moléculaire)2016! Liang!CHANG!!
Methyl!Coumalate!Involved!MoritaRBaylisRHillman!Reaction!
[email protected] !PhD!advisors:!Dr.!Luc!Dechoux,!Pr.!Serge!Thorimbert!
Laboratory:)IPCM)Chembio)group)
!!The!Morita,Baylis,Hillman!(MBH)!reaction!is!an!atom,economic!carbon,carbon!bond,forming!reaction.!!!In!general!it!could!be!described!as!a!coupling!between!activated!electron!deficient!alkenes!(alkynes)!and!electrophiles!catalyzed!by!Lewis!base!providing!a!classes!of!functionalized!molecules.1!!Different! types! of! activated! alkenes! such! as! cyclic! and! acyclic! derivatives! have! been! used! in! the!MBH!reaction.! In! spite! of! the! advances! reached,! MBH! reactions! with! aromatic! heterocycles! have! not! been!reported!to!date.!!!Prepared!from!malic!acid,!methyl!coumalate! is!a!biorenewable!heterocyclic!compound,!which!provide!an!environmentally,benign!approach!for!organic!synthesis.2!!We!now!report!a!study!of!the!behavior!of!methyl!coumalate!under!Morita,Baylis,Hillman!conditions!upon!reaction!with!imines!and!aldehydes.!!!
!!
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!
Acknowledgment:!Omar!KHALED!for!HRMS,!Lise!Marie CHAMOREAU!for!XRD,!CSC!for!scholarship.!UPMC!&!CNRS!for!financial!support.!!
1 D. Basavaiah, B. S. Reddy, S. Badsara, Chem. Rev. 2010, 110, 5447. 2 a) J. Lee, G. Kraus. Green Chem. 2014, 16, 2111. b) G. Kraus, S. Riley, T. Cordes. Green Chem. 2011, 13, 2734. c) S.
Zheng, X. Lu. Org. Lett. 2009, 11, 3978. d) J. Agarwal, O. Bayounes, S. Thorimbert, L. Dechoux. RSC Advances. 2014, 4, 2272.
Page 17
Journées)de)Chimie)Moléculaire)2016! Alexandra!FERALDI!!
Ring!Contraction:!Synthesis!of!functionalized!αR(trifluoromethyl)Rpyrrolidines!and!
piperidines!
[email protected] !PhD!advisor:!Prof.!Janine!Cossy,!Dr.!Domingo!Gomez!Pardo!
Laboratoire)de)Chimie)Organique,)Institute)of)Chemistry,)Biology)and)Innovation)(CBI),)UMR)8231)
ESPCI)Paris/CNRS)/PSL*)Research)University,))
10)rue)Vauquelin,)75231)Paris)Cedex)05)
!Introduction!of!a!fluorine!atom!on!molecules!often!improves!their!biological!properties!by!increasing!their!hydrophobicity,! their! thermal! and! metabolic! stability.! Therefore,! it! became! obvious! that! fluorinated!compounds!have!a!remarkable!record!in!medicinal!chemistry!and!will!play!a!continuous!role!in!providing!lead!compounds! for! therapeutic! applications.1! Amongst! these! compounds,! amines! possessing! an! α,trifluoromethyl! substituent!are!of! great! importance!as! they!are!present! in!a! variety!of!biologically!active!compounds.2!!In!this!context,!a!series!of!2,substituted!2,(trifluoromethyl)pyrrolidines!containing!a!quaternary!center!at!the!C2!position!were!synthesized!from!3,hydroxy,3,(trifluoromethyl)piperidine.!The!reaction!proceeds!via!a!ring!contraction!to!form!an!aziridinium!intermediate!which,!after!the!attack!of!a!nucleophile,!gives!the!desired!substituted! pyrrolidines! (eq! 1).3! In! addition,! this! ring! contraction! affords! 2,substituted!2,(trifluoromethyl)piperidines!from!3,hydroxy,3,(trifluoromethyl)azepane!(eq!2).!It!is!worth!mentioning!that!a!chirality!transfer!takes!place!during!this!ring!contraction!
!
!
!
!
!
!!! !
1 For fluorine in medicinal chemistry see: [a] H.-J. Bohm, D. Banner, S. Bendels, M. Kansy, B. Kuhn, K. Muller, U.
Obst-Sander, M. Stahl, ChemBioChem 2004, 5, 637–643, [b] K. L. Kirk, Org. Process Res. Dev. 2008, 12, 305–321, [c] S. Purser, P. R. Moore, S. Swallow, V. Gouverneur, Chem. Soc. Rev. 2008, 37, 320–330.
2 [a] Fluorine- Containing Amino Acids : Synthesis and Properties (Eds.: V. P. Kukhar, V. A. Soloshonok), Wiley, New York, 1995, [b] G. Chaume, N. lensen, N. Caupene, T. Brigaud, Eur. J. Org. Chem. 2009, 2009, 5717–5724.
3 A. Feraldi-Xypolia, D. Gomez Pardo, J. Cossy, Chem. Eur. J. 2015, 21, 12876–12880.
NBn
OHCF3
NBn
CF3 NBn
CF3Nu (eq-2)
Nu
22'
NBn
CF3
NuNBn
CF3
NBn
CF3OH
2
2'
Nu
(eq1)
Page 18
Journées)de)Chimie)Moléculaire)2016! Thomas!AUBINEAU!!
Formation!of!NRcontaining!heterocycles!
[email protected] !PhD!advisor:!Pr.!Janine!Cossy!
Laboratoire)de)Chimie)Organique)–)Institute)of)Chemistry,)Biology)and)Innovation)(CBI))–)UMR8231)f)ESPCI)Paris,)CNRS,)
PSL)Research)University)
10)rue)Vauquelin)–)75231)Paris)Cedex)05)
!Nitrogen,containing!six,membered!heterocycles!are!widely!encountered!in!the!structure!of!pharmaceutical!and!agrochemical!products.1!As!such,!new!methods!to!access!these!compounds!are!desirable.!We!focused!our! attention! on! the! formation! of! heterocycles! possessing! two! heteroatoms! such! as! piperazines! and!morpholines.!!The! formation! of! piperazines! derivatives!was! envisioned! by! using! the! powerful! alkynylating! hypervalent!iodine,based! reagent! trimethylsilylethynylbenziodoxolone! (TMS,EBX).! After! having! shown! the!chemoselectivity!of!this!reagent!towards!sulfonylated!amines!in!comparison!with!carbamates!or!amides,!a!one,pot!cyclization!leading!to!tetrahydropyrazines!from!orthogonally!protected!ethylene,diamines!has!been!developed!(Scheme 3).2!!
Scheme 3
!In!addition,!2,6,morpholines!were!synthesized!by!taking!advantage!of!the!metal,catalyzed!activation!of!allylic!alcohols.3! A! thermodynamic! equilibrium! leading! to! the! formation! of! cisfmorpholines! with! good!diastereoselectivities!has!been!highlightened!(Scheme 4).!!
Scheme 4!
!
!
!
! !
1 E. Vitaku, D. T. Smith, J. T. Njardarson, J. Med. Chem. 2014, 57, 10257-10274. 2 T. Aubineau, J. Cossy, Chem. Commun. 2013, 49, 3303-3305. 3 J. Cornil, L. Gonnard, C. Bensoussan, A. Serra-Muns, C. Gnamm, C. Commandeur, M. Commandeur, S. Reymond,
A. Guérinot, J. Cossy, Acc. Chem. Res. 2015, 48, 761-773.
NH
HN
N
N
N
HN
R
TMS-EBX
NaH
NaH
(1 equiv)
(2 equiv)
NaH(1 equiv)
R
R
Ts
Ts
RTs
DMF
IO TMS
TMS-EBX
O
-NR = amides, carbamates
1,2
1,2
1,2
N
Ts
R
OH
OH O
N
R
Ts
FeCl3.6H2O (5 mol %)
CH2Cl2, 50 °C, 2 h
cis/trans = 90/10 to 99/1
H H
Page 19
Journées)de)Chimie)Moléculaire)2016! Ludovic!LELEU!!
Kojic!acid!:!a!natural!compound!for!organic!synthesis!and!access!to!
biologically!active!molecules!!!
ludovic.leleu@chimie,paristech.fr!PhD!advisor:!Christian!Girard!
UTCBS,)U)1022)INSERM,)UMR)8258)CNRS,)Chimie)Paristech,)11)rue)Pierre)et)Marie)Curie,)75005)Paris)
!Kojic!acid! is!a!by,product!of!alcoholic! fermentation! industries.! It! comes! from!hexose!and!glucose!
transformations,!especially!during!rice!fermentation.1!This!substituted!pyranone!was!considerably!studied!in!literature!for!its!various!properties,!and!is!often!used!for!its!actions!on!pigmentation!in!food!and!cosmetic!industries.2!(Food!preservation!/!skin!whitening)!
Structure!and!reactivity!of!kojic!acid!allow!further!transformations!and!the!synthesis!of!structurally!diversified!polycyclic!compounds!will!be!presented.!These!heterocycles!can!be!obtained!in!several!steps!using!typical! reactions! like! [5+2]! cycloadditions,! Diels,Alder,! [5+2]/[4+2]! tandem! cycloadditions.3,4! All! the!compounds!were!produce!in!a!classical!organic!chemistry!manner!and!the!use!of!specific!equipments!like!microwave!reactor! !and!continuous,flow!chemistry!equipments!were!also!developing!to!obtain!syntheses!more!efficient!and!more!specific.!
!!
!
!!
! !
1 R. Bentley, Nat. Prod. Rep., 2006, 23, 1046–1062. 2 M. Rosfarizan, M. Mohd Shamzi, S. Nurashikin, M. Madihah Mohd Salleh, A. B. Arbakariya, Biotech. Mol. Biol.
Rev., 2010, 5, 24-37.!3 A. Rumbo, L. Castedo, A. Mourino, J. L. Mascarenas, J. Org. Chem., 1993, 58, 5585-5586. 4 J. R. Rodriguez, A. Rumbo, L. Castedo, J. L. Mascarenas, J. Org Chem., 1999, 64, 966-970.
Page 20
Journées)de)Chimie)Moléculaire)2016! Benjamin!FLAMME!!
Rational!design!of!5V!organic!electrolytes!Benjamin.flamme@chimie,paristech.fr!
Mansour!HADDAD1,!Phannarath!PHANSAVATH1,!Virginie!VIDAL1,!Alexandre!CHAGNES1,2!1Chimie)ParisTech,)PSL)Research)University,)CNRS,)Institut)de)Recherche)de)Chimie)Paris)(IRCP),)Ff75005)Paris,)France.)
2Réseau)sur)le)Stockage)Electrochimique)de)l’Energie)(RS2E),)FR)CNRS)3459,)France.)
!The! development! of! new! technologies! for! electrochemical! energy! storage! is! one! of! the! main!
challenges!of!the!next!decades.!Many!hopes!now!rely!on!lithium,ion!batteries!(LiBs)!that!have!invaded!the!market!of!laptops!and!which!appear!to!be!the!best!choice!in!a!short!term!for!electric!vehicles,!and!perhaps!for! network! applications! (electricity! storage! from!wind! turbines! or! solar! cells! for! example).!Many!works!concern!the!search!for!cathodes!with!high,energy!density!but!only!few!studies!focus!on!the!synthesis!of!new!dipolar! aprotic! organic! solvents! for! LiBs! electrolytes.! Thus,! there! is! a! need! to! deviate! from! traditional!approaches! for! identifying! new! electrolytes! stable! to! high! voltage! that! are! based! on! "Trial! and! Errors"!approaches.!Research!groups!from!organic!chemistry,!electrochemistry,!solution!chemistry,!thermodynamics!and! theoretical! chemistry! were! included! in! this! multidisciplinary! project.! The! present! poster! aims! at!presenting!recent!advances!on!the!design!of!new!organic!electrolytes!for!high,voltage!batteries.!!
First,! a! critical! review! of! the! physicochemical! and! electrochemical! properties! of! the! organic!electrolytes!was!conducted!(boiling!and!melting!points,!viscosity,!ionic!conductivity!in!the!presence!of!lithium!salts,!oxidation!potential,!etc.).!This!critical!review!highlights!the!lack!of!homogeneity!in!the!literature!data!for! performing! rational! design! of! electrolytes! by! means! of! quantitative! structure,property! relationship!calculations! (QSPR).! Therefore,! these! data! were! completed! and! homogenized! by! performing! new!experiments.!In!particular,!more!than!20!new!dipolar!aprotic!organic!solvents!based!on!sulfone!moiety!were!synthesized!and!characterized.!!
!
!!
Second,! the! physicochemical! properties! of! these! new! dipolar! aprotic! organic! solvents! including!viscosity,! ionic! conductivity! and! their! electrochemical! behaviors! on! graphite,! ! Nickel! Manganese! Cobalt!(NMC)!and!Lithium!Rich!electrodes!as!well!as!platinum!and!glassy!carbon!electrodes!will!be!presented!and!discussed.!!
Finally,!we!will!highlight!the!main!drawbacks!and!the!next!challenges!in!the!design!of!new!organic!electrolytes!for!5V!lithium,ion!batteries.!!!
!
K. Xu, Chem. Rev., 2004, 104, 4303−4417, Y. Sasaki, Electrochemistry, 2008, 76, 2-15 A. Abouimrane, I. Belharouak, K. Amine, Electrochem. Commun., 2009, 11, 1073–1076, C.-C. Su, M. He, P. Redfern, L. A. Curtiss, C. Liao, L. Zhang, A. K. Burrell, Z. Zhang, ChemElectroChem., 2016, DOI: 10.1002/celc.201500550.! !
Page 21
Journées)de)Chimie)Moléculaire)2016! FrançoisRXavier!GUILLON!!
Electrochemical!microRNA!biosensors:!
an!ergonomic!miniaturized!twoRelectrode!setup!
fx.guillon@chimie,paristech.fr!PhD!advisor(s):!Mathieu!LAZERGES!(MCF!Paris!Descartes),!Fethi!BEDIOUI!(DR!CNRS)!
Laboratory:)UTCBS)–)UMR)8258)–)INSERM)U1022)
École)Nationale)Supérieure)de)Chimie)de)Paris)
)11)rue)Pierre)et)Marie)Curie,)75231)Paris)Cedex)05)
)
MicroRNAs!are!RNAs!from!18!to!23!bases!involved!in!many!biological!processes.!They!particularly!regulate!gene!expression!by!partial!matching!with!messenger!RNAs1.!They!were!recently!discovered!and!they!are!the!last!biological!class!of!molecules!making!up!the!genetic!code.!They!can!be!found!in!different!biological!liquids,!they!enable!the!diagnosis!of!several!pathologies2!and!can!be!considered!as!excellent!biomarkers3.!
However! quantification! of!microRNAs,! from!10,12! to! 10,18!M! in!complex! matrixes! is! a! real! challenge! since! it! requires! the!development! of! a! specific! and! very! sensitive!measurement! tool.!Electrochemical!biosensors!and!particularly!the!long,range!electron!transfer!DNA,sensors!offer!an!efficient!way!to!do!so4.!In!this!study!we!develop!an!ergonomic!DNA,biosensor!based!on!a!two,electrode!electrochemical!setup!and!using!a!microelectrode!as!working!electrode,!well!adapted!for!detection!in!microliter!samples!and! miniaturization.! A! 23,base! DNA,probe! self,assembled!monolayer!was! first! formed!onto!a!50!µm,diameter!gold!surface.!The!microelectrode!extremity!was!then!immersed!in!a!50!µL!DNA,target! solution! drop! itself! deposited! onto! a! 5!mm,diameter! gold!counter! electrode.! Transduction! occurs! via! long,range! electron!
transfer,!which! is!enhanced!subsequently! to!hybridization,!due!to!DNA,base!π,stacking5.!Single!mismatch!detection!of! this! first!prototype!was!matched!at! room! temperature! in! the!nanomolar! range!without!any!optimization.!!!!!!!!!!!!Aknowledgment: FXG!acknowledges!support!from!the!program!«Investissements!d’Avenir!»!launched!by!the!French!Government!and!implemented!by!ANR!with!the!references!ANR,10,LABX,XXX!and!ANR,10,IDEX,0001,02!PSL!for!PhD!fellowship! !
1 H. Vaucheret, C. Béclin, M. Fagard, Journal of Cell Science 2001, 114, 3083-3091 2 J. Lu, G. Getz, E. Miska, Nature 2005, 435, 834-838 3 Q. Shi, X. Yang, D. Mendrick, Biomarkers in Medicine 2013, 7, 307-315 4 S. Kelley, E. Boon, J. Barton, Nucleic Acids Research 1999, 27, 4830-4837 5 K. Hashimoto, K. Ito, Y. Ishimori, Analytical Chemistry 1994, 66, 3830-3833
Figure 1: Scheme of a long-range electron transfer RNA biosensor with redox intercalator
Page 22
Journées)de)Chimie)Moléculaire)2016! Xia!WANG!!
Photocatalytic!CO2!reduction!by!multinuclear!metal!complexes!
Xia.wang@college,de,france.fr!PhD!advisor:!Marc!FONCTECAVE!
Laboratory)of)Chemistry)of)Biological)Processes)
11)Place)Marcelin)Berthelot)75005)Paris)
!The!general!field!of!energy!storage!is!crucial!to!the!successful!development!and!implementation!of!renewable!energy!technologies.!Storing!energy!in!the!form!of!chemical!bonds!allows!for!the!production!of!energetically!dense!fuels.!Carbon!dioxide,!through!its!reduction,!is!an!ideal!candidate!as!a!carbon!source!for!such!fuels.!The!metal,based!molecular!approach!to!the!development!of!catalysts!has!long!been!favored!for!fundamental!studies!due!to!the!facile!modification!of!the!catalytic!active!sites,!which!is!ideal!for!investigating!fundamental!questions!such!as!selectivity!and!mechanism.1!
Since! 2005,! Ishitani! and! co,workers! have! been! focusing! on! Re,Ru! bimetallic! complexes! for!photocatalytic! CO2! reduction,! where! the! Re! center! serves! as! a! catalyst! and! the! Ru! center! serves! as! a!photosensitizer.2! Inspired! by! their! study,! a! series! of! Co,Ru,! Ru,Ru! and! Ru,Co,Ru! complexes! have! been!synthesized,! and! the! photocatalytic! activities! for! CO2! reduction! are! being! studied.! Having! surveyed! and!identified!a!set!of!optimal!conditions,!photokinetic!studies!on!each!complex!were!investigated.!After!16!hours!irradiation!up!to!332!turnover!numbers!(TONs)!for!formate!was!observed!for!a!Ru,Co,Ru!complex,!and!60!TONs!for!CO!for!a!Co,Ru!complex.!No!products!were!formed!in!the!absence!of!either!the!complexes!or!light.!Also!the!addition!of!mercury!into!our!photocatalytic!system!did!not!affect!the!amount!of!products!formed.!Taken! together,! it! suggested! that! the! catalysts! involved! in! CO2! photoreduction! were! the! molecular!complexes.!Studies!on!effects!of!the!peripheral!ligands!and!the!central!bridge!between!the!metals!indicated!that!the!ligands!influenced!the!selectivity!between!carbon,based!products!and!H2!production.!!!!!!!
!!
!
!
!
!
!
!
!
!
!
Aknowledgment:!
I!acknowledge!D.!Meyer!(DR,!ICSM)!for!providing!complexes,!and!Paris!Sciences!et!Lettres!(PSL)!Research!University!for!financial!support.! !
1!X.!Wang,!M.!Fontecave,!et!al.,!Chem.)Soc.)Rev.!(submitted)!2!O.!Ishitani,!et!al.,!!Inorg.)Chem.,!2005,!44,!2326,2336!!
N
N
NH
N
N
N
N
HN
R1
R2
A B
A:!Ru(bpy)2,!Ru(4,4’,Mebpy)
2!
B:!Co(phen)2,!Co(tpy)Cl,!Ru(bpy)
2,!Ru(4,4’,Mebpy)
2!
R1:!H,!tBu!
R2:!H,!OH!
Page 23
Journées)de)Chimie)Moléculaire)2016! Pascal!MATTON!!
Glycolipid!functionalized!microdroplets!for!cells!vectorization!
[email protected] !PhD!advisor(s):!Jean!Maurice!MALLET1,!Jacques!FATTACCIOLI2!
1Laboratoires)des)biomolecules,)CNRS)UMR)7203,)Department)of)Chemistry,)ENS,)24)rue)Lhomond,)Paris)75005)2Laboratoire)P.A.S.T.E.U.R,)CNRS)UMR)8640,)UPMC,)Department)of)Chemistry,)ENS,)24)rue)Lhomond,)Paris)75005)
)
! Some!pathogens!or!tumor!cells!escape!the!immune!system!because!the!immune!cells!misrecognize!them.!Therapeutic!approaches,!promoting!the!recognition!of!these!poorly!immunogenic!peptides!or!proteins!are!thus!very!attractive.11!The!strategy!is!then!to!process!directly!peptides!or!proteins!through!the!immune!system.!To!this!end,!some!systems!have!been!described,!based!on!lipopolyplexe2!or!nanoparticle3.!We!propose!to!use!an!oil!droplet!based!system.!! Among!the!microparticles,!vegetal!oil!microdroplets!have!numerous!advantages!over!solid!microparticles.!Made!of!natural!triglycerides,!they!are!biocompatible!and!biodegradable;!their!liquid!nature!gives!them!a!greatly!stealth!(no!adsorption!of!proteins!on!their!surface,!low!recognition!by!immune!cells).!A!previous!work,!with!IgG,functionalized!oil,in,water!emulsion!droplets!for!phagocytosis!studies!with!macrophage,!has!shown!that!during!the!recognition!by!macrophages,!IgGs!are!driven!and!concentrate!in!the!contact!zone!by!interaction!and!thus!increase!the!sensitivity.!They!are!ideal!platforms!to!build!multifunctional!assemblies!for!vectorization4.!! The!goal!of!this!project!is!to!build!and!use!for!vectorisation!a!lipidic!shuttle:!Oil!microdroplets!(diameter!:!5,7!µm),!functionalized!with!the!required!immunogenic!molecules!and!with!molecules!determining!their!behavior!in!front!of!immune!cells,!in!particular!different!concentration!of!glycolipid!which!is!a!cell!lectins!ligand!(Fig!1).!!
!!
Figure!1!:!(left)!lectins!interaction!with!fluorescence,labeled!glycolipid!in!oil!droplet.!(right)!:!Micro!droplet!functionalized!with!a!fluorescent!mannolipide!viewed!in!fluorescent!microscopy.! ! In!the!preliminary!work!reported!here,!we'll!present!the!synthesis!and!physical!properties!(CMC,!surface!tension,!...)!of!mannose!and!galactose!glycolipids.!The!glycolipids!were!functionalized!by!a!robust!and!hydrophobic!fluorophore!in!order!to!verify!their!correct!functionalization!at!the!surface!of!the!droplet!(figure!1,!right).!The!galacto!and!manno!labeled!droplets!were!then!brought!into!contact!with!fluorescent!soluble!lectins:!PNA!(for!galactose)!and!ConA!(for!mannose),!and!specific!recognitions!were!observed.!Based!on!this!encouraging!observation,!we!are!now!studying!interactions!of!the!droplet!with!cells.!! !
1 Tagliamonte, M.; Petrizzo, A.; Tornesello, M. L.; Buonaguro, F. M.; Buonaguro, L. Hum. Vaccines Immunother.
2014, 10 (11), 3332. 2 Midoux, P.; Pichon, C. Expert Rev. Vaccines 2015, 14 (2), 221. 3 Zhao, L.; Seth, A.; Wibowo, N.; Zhao, C.-X.; Mitter, N.; Yu, C.; Middelberg, A. P. J. Vaccine 2014, 32 (3), 327. 4 Ben M’Barek, K.; Molino, D.; Quignard, S.; Plamont, M.-A.; Chen, Y.; Chavrier, P.; Fattaccioli, J. Biomaterials 2015,
51, 270.
Fluorescent+lec,n+
Droplet++
Fluorescent+glycolipid++
Page 24
Journées)de)Chimie)Moléculaire)2016! Thomas!DENEFLE!!
TSPR1!mimetic!peptides!inducing!selective!apoptosis!of!cancer!cell!lines:!design,!
synthesis!and!structureRactivity!relationship!studies!!
[email protected] !PhD!advisor:!Pr.!Philippe!Karoyan!
!LBM)–)site)GSK,)25f27)avenue)du)Québec,)91140)VillebonfSurfYvette,)France.)
Sorbonne)Universites,)UPMC)Univ)Paris)06,)Ecole)Normale)Superieure,)CNRS,)Laboratoire)des)Biomolécules)(LBM),)4)
place)Jussieu,)75005)Paris,)France))
Departement)de)Chimie,)Ecole)Normale)Superieure,)PSL)Research)University,)UPMC)Univ)Paris)06,)CNRS,)Laboratoire)
des)Biomolecules)(LBM),)Paris,)France))
)
)
!!!!!!!!!!!
!!
Figure:!TSP,1!derived!peptide!inducing!selective!apoptosis!of!tumor!cells!in)vitro.!!
Thrombospondin!1!(TSP,1),!a!multidomain!glycoprotein!from!the!extracellular!matrix,!is!able!to!bind!to!many!cell! surface! receptors! such! as! CD47.! The! TSP,1/CD47! interaction! triggers! programmed! cell! death.! We!demonstrated!that!4N1K,!a!short!peptide!derived!from!C,terminal!binding!domain!of!TSP,1,!induced!selective!apoptosis! of! numerous! cancer! cell! lines! sparing! normal! cells.1! In! order! to! improve! the! pharmacological!properties!of!this!compound,!we!initiated!a!complete!structure,activity!relationship!study!through!rational!design.!As!part!of!my!PhD,!this!work!leads!to!the!discovery!of!active!and!serum,stable!new!peptides!derived!from!this!protein,protein!interaction!epitope!that!will!be!presented!herein.2!
!
Acknowledgments:!!
INCa,!ANR,!Labex!Michem!and!SATT!Lutech!(Michael!Machicoane)!are!gratefully!acknowledged!for!financial!support!and!Pr.!Philippe!Karoyan!deeply!thanks!GSK!for!hosting!and!partnership.!! !
1 a) Susin, S-A. ; Merle-Beral, H. ; Launay, P. ; Karoyan, P. PCT Int. Appl. 2013, WO 2013182650 A1 20131212. b) Martinez-Torres, A-C. ; Quiney, C. et al. PLoS Med. 2015, 12(3): e1001796. 2 Denèfle, T. et al. 2016. Submitted manuscript.
Page 25
Journées)de)Chimie)Moléculaire)2016! Sébastien!CARDON!!QUANTIFICATION!OF!THE!INTERNALIZATION!EFFICACY!OF!HOMEOPROTEINS!AND!
DERIVEDRCELL!PENETRATING!DOMAINS!
[email protected] !
Sandrine!Sagan!
Laboratoire)des)Biomolécules,)Sorbonne)UniversitésfUPMC,)ENS)Department)of)Chemistry)PSLfResearch)University,)
CNRS)UMR7203,)Paris,)France)
Homeoprotein! (HP)! transcription! factors! and! HP,derived! homeodomains! (HD)! have! the! characteristic! of!
being!secreted!and!internalized!by!eukaryotic!cells![1].!The!internalization!mechanism!of!these!proteins!and!
peptides!is!not!yet!fully!understood.!!
At!the!molecular!level,!it!was!found!that!the!16!amino!acid!long!third!helix!of!HD!provides!the!driving!force!
for! internalization! [2].! Interaction!with! cell,surface,!which! is! the! first! step! in! the! internalization! process,!
predominantly!relies!on!carbohydrates!and!was!reported!to!be!predominant!for!HD![3],!Penetratin,!and!HPs!
binding!to!distinct!cell!types.!!
!
The! aim! of! the! work! is! to! delineate! the!mechanisms! of! entry! of! HPs,! HDs! and! derived,cell,penetrating!
peptides! at! the! molecular! level.! We! chose! Engrailed! 2! as! a! representative! HP.! Quantification! of! the!
internalization!efficacy!of! these!proteins,!analysis!of! their! secondary! structure,!when! free! in!buffer,!or! in!
interaction!with!model!membranes,! together!with!thermodynamic!analyses!of! their! interactions!with!cell!
surface!sugars!are!the!first!steps!of!this!study.!!
!
Aknowledgment:!Laura!Molina,!Alain!Joliot,!Fabienne!Burlina,!Gérard!Bolbach,!Astrid!Walrant,!Olivier!Lequin,!
Ludovic!Carlier,!Sandrine!Sagan!!
!
! !
Page 26
Journées de Chimie Moléculaire 2016 Thomas DRIANT
On the influence of the protonation states of active site residues on AChE
reactivation: a QM/MM approach
[email protected]
PhD advisor(s): Etienne Derat
Laboratory: Institut Parisien de Chimie Moléculaire UMR8232 Université Pierre et Marie Curie, 4 Place Jussieu
Structure optimisée du réactif de la réactivation par la 2-PAM de l’AChE inhibée par le VX.
Acetylcholinesterase (AChE) is an enzyme of the serine hydrolase superfamily and a mediator of the signal
transmission at cholinergic synapses.1 This enzyme is vulnerable to inhibition by organophosphate (OP)
compounds, especially combat gasses such as Sarin, VX, Tabun and Soman. The inhibition of AChE results in
the over activation of the synapses which leads to death by respiratory arrest.2 The covalent inhibition of
AChE does not revert spontaneously and known reactivator compounds have limited effects.3 We used an
hybrid QM/MM (B3LYP-D3:CHARMM) method to perform reactivation simulations of VX inhibited AChE by
2-PAM. During those simulation we studied the protonation state of a glutamate in close proximity with the
active site, Glu202. This work uncovers for the first time the key role of this residue in AChE reactivation.
The deprotonation of 2-PAM, an important step towards reactivation, was also explored in both
protonation states of Glu202. Those simulations allowed for a broader view of the effect of protonation
states in the active site. They allow us to conclude on the protonation states that make reactivation
possible.
Aknowledgment: DGA, Florian Nachon, Pierre-Yves Renard, MACO team
1 Quinn, D. M. Chem. Rev. 1987, 87 (5), 955–979. 2 Marrs, T. C.; Maynard, R. L. Cell Biol Toxicol 2013, 29 (6), 381–396. 3 Mercey, G.; Verdelet, T.; Renou, J.; Kliachyna, M.; Baati, R.; Nachon, F.; Jean, L.; Renard, P.-Y. Acc. Chem. Res. 2012, 45 (5), 756–766.
Page 27
Journées)de)Chimie)Moléculaire)2016! Mathilde!BELNOU!!
Modulation!of!the!Calmodulin!Binding!Domain!of!the!protein!FKBP52!
[email protected] !Yves!Jacquot!
Laboratoire)des)biomolécules,)4)Place)Jussieu,)Tour)23f33)5ème)étage)
!
! FKBP52!(FK506+Binding!Protein)!is!an!immunophilin!protein!of!52!kDa!that!binds!immunosuppressant!
macrolide!drugs!such!as!rapamycin.!FKBP52!is!composed!of!four!distinct!domains:!(i)!an!FK1!domain,!which!
shares! peptidylprolyl! isomerase! (PPIase! or! rotamase)! enzymatic! activity! and! that! recognizes! macrolide!
immunomodulators!and!other!proteins!such!as!steroid!hormone!receptors,!(ii)!an!FK2!domain!that!binds!ATP!
and!GTP,!(iii)!a!tetratricopeptide!repeat!domain!(TPR)!that!recruits!the!heat+shock!protein!Hsp90!and!(iv)!a!
putative!Ca2++calmodulin+binding!domain1,2.!!
Calmodulin!is!a!small!calcium!sensing!protein,!which!participates!in!various!signalling!processes.!We!
are! interested! in! the! interaction! of! FKBP52! with! Calmodulin3.! In! the! present! research! project,! we! have!
synthesised! a! small! library! of! FKBP52+derived!peptides! and! tested! their! interaction!with! Calmodulin! using!
different! biophysical! approaches! such! as! Fluorescence! spectroscopy,! NMR! spectroscopy! and! Isothermal!
Titration!Calorimetry.!We!have!identified!FKBP52!TPR!domain+derived!peptides!that!bind!calmodulin!with!a!Kd!
∼!150!nM!and!a!stoechiometry!of!1:1.!This!process!is!calcium!dependent!and!the!mode!of!interaction!of!the!
peptide!with!Ca2++calmodulin!seems!canonical.!!
!!!!
!
!
!
!
!
!
!
!
!
!
!
!
!
!
Aknowledgments:!LBM!team!1:!Yves!Jacquot,!Cillian!Byrne,!Caroline!Bushdid,!LBM!team!3:!!Ludovic!Carlier,!Institut!Professeur!Baulieu:!E.E.!Baulieu,!Béatrice!Chambraud,! IBPS:!Gérard!Bolbach,!Emmanuelle!Sachon,!Gilles!Clodic,!Lucrèce!Matheron,!IBBMC:!Michel!Desmadril,!Magalie!Nicaise,!INSA:!Guy!Lippens!! !
1 A.Kamah et al, J. Mol. Biol., 2016 2 J. Giustiniani et al., The FASEB Journal, 2015,29 3 O’Day, Journal of Alzheimer’s disease, 2015, 46, 553-569
�(15
N) [
ppm
]
�(1H) [ppm]
Residue number
A
C
amid
e C
SP
[ppm
]
�(1H) [ppm]
�(13
C) [
ppm
]
B
D
Ca4CaM:FKBP52{278-300} 1:0 Ca4CaM:FKBP52{278-300} 1:1
N-ter
C-ter
hydrophobic pockets A57
G113 Ca4CaM:FKBP52{278-300} 1:0 Ca4CaM:FKBP52{278-300} 1:1
F19
V55
M71
M109
M145
A147
0,0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
0,9
0 10 20 30 40 50 60 70 80 90 100 110 120 130 140
Methionine methyl groups of Ca4CaM
Synthetic!FKBP52+derived!Calmodulin!binding!peptide!!
Page 28
Journées)de)Chimie)Moléculaire)2016! Caroline!THEBAULT!!
UltraRMagnetic!Liposomes!and!their!in)vivo!Guidance!Monitoring!by!MRI!for!
Cancer!Therapy!
caroline.thebault@chimie,paristech.fr!!PhD!advisors:!Bich,Thuy!DOAN!and!Christine!MÉNAGER!!
))Chimie)ParisTech,)PSL)Research)University,)Unité)de)Technologies)Chimiques)et)Biologiques)pour)la)Santé)(UTCBS),)Ff
75005)Paris,)France)Sorbonne)Universités,)UPMC)Univ)Paris)06,)CNRS,))Laboratoire)PHENIX,)Case)51,)4)place)Jussieu,)Ff75005)Paris,)France))
)))
Theranostic!systems!are!developed!to!monitor!a!treatment!in)vivo!according!to!their!abilities!for!both!imaging!and! therapy1.! We! propose! an! innovative! strategy! to! treat! colon! cancer! with! the! design! of! magnetic!thermosensitive!liposomes2!that!enable!to!target!a!superficial!tumor!under!a!magnetic!field!gradient!and,!after!accumulation,!to!deliver!an!antitumoral!drug!by!High!Intensity!Focused!Ultrasounds!(HIFU)!application.!These! objects! can! be! track! in) vivo! due! to! their! imaging! properties.! In! this! study,! we! demonstrate! the!significant!increase!of!accumulation!of!Ultra,Magnetic!Liposomes!(UML)!in!CT26!murine!colon!tumor!using!Magnetic!Targeting!(MT)!compared!with!passive!Enhanced!Permeability!Retention!(EPR)!effect.!UMLs!are!highly!loaded!with!magnetic!nanoparticles!of!iron!oxide!(γ,Fe2O3)!enabling!both!magnetic!targeting!and!in)vivo!monitoring!by!MRI.!Liver!up,take!of!UMLs!after!I.V.!injection!was!followed!with!dynamic!susceptibility!contrast! imaging! in!MRI.!UMLs!accumulation! in! tumors!was!visualized!by!breath,triggered!multislice!T2*,weighted!MRI!with!adapted!dynamic!follow!up!in!time!at!7T.!The!figure!below!shows!an!MRI!slice!of!mouse!(A)!before!injection!(Reference!Tumors)!and!(B)!30min!after!the!injection!of!UML!with!a!Magnetic!Targeting!on!the!right!tumor!and!passive!accumulation!on!the!left!one.!!!
!!
MRI! image! by! low! percentile! processing! on! in) vivo! images! enabled! us! to! evaluate! the! difference! of!accumulation!between!Magnetic!Targeting!and!EPR!effect.!The!addition!of!a!fluorescent!NIR!Cy5.5!probe!on!the!liposome!membrane!allowed!the!visualization!of!UMLs!by!fluorescent!confocal!microscopy!to!confirm!the! guidance! of! the!whole! liposome.!Ex) vivo! iron! dosage! by! ICP,AES,! Cy5,5! quantification! and! histology!confirmed! the! increase! of! accumulation! with! Magnetic! Targeting.! Co,encapsulation! of! magnetic!nanoparticles! with! an! antitumoral! drug! gave! theranostic! properties! to! our! thermosensitive! liposomes.!Application!of!HIFU!can,!then,!be!used!in!the!tumor!for!an!active!release!of!the!drug!in!the!region!of!interest!for!the!development!of!an!innovative!therapy.!Functional!MRI!methods!will!enable!to!study!the!impact!of!antitumoral!drugs!on!the!tumor.!!
Aknowledgment:!
This!work!was!financially!supported!by!the!labex!MICHEM,!UPMC.!We!thank!our!collaborators!N.!Mignet,!G.!Ramniceanu,!J.!Seguin,!C.!Beauvineau,!C.!Girard,!B.!Larrat.!! !
1 B. Sumer, J. Gao, Nanomedicine, 2008, 3, 137-140 2 G. Béalle, R. Di Corato, J. Kolosnjaj-Tabi, V. Dupuis, O. Clément, F. Gazeau, C. Wihelm, C. Ménager, Langmuir,
2012, 28, 11834-11842.
Page 29
Journées)de)Chimie)Moléculaire)2016! Frédéric!THIEBAUT!!
Identification!of!rare!DNA!base!protein!partner!using!photolabeling!and!mass!
spectrometry!
[email protected] !PhD!advisor(s):!Dominique!Guianvarc’h,!Carole!Saintomé!
Laboratory:)Laboratoire)des)BioMolécules,)UMR7203,)Université)Pierre)et)Marie)CuriefParis)6fENSfCNRS,)4,)place)
Jussieu,)75252)Paris)Cedex)05)
!Over!the!past!few!decades,!DNA!methylation!at!the!5,position!of!cytosine!(5,methylcytosine,!5mC)!
has!emerged!as!an!important!epigenetic!modification!that!plays!essential!roles!in!development,!aging!and!disease.!However,! the!mechanisms!controlling!5mC!dynamics! remain!elusive.!Recent!studies!have!shown!that! ten,eleven! translocation! (Tet)! proteins! can! catalyze! 5mC! oxidation! and! generate! 5mC! derivatives,!including!5,hydroxymethylcytosine!(5hmC)!.!!
5hmC! was! until! recently! believed! to! be! a! minor! modification,! resulting! of! oxidative! damage.!However,! results!published! in!2009!have!challenged!this!understanding! (1,!2).! In! fact,!5hmC! is!abundant! in!some!cell!types!and!its!formations!results!from!an!active!process.!These!recent!discoveries!raise!the!question!of!the!biological!role!of!5hmC.!Indeed,!If!the!role!of!5mC!in!gene!expression!regulation!is!well!established,!the!biological!role!of!5hmC!is!still!a!hot!topic.!Its!implication!in!the!DNA!demethylation!process!seems!a!major!reported!activity.!In!the!study!context!of!this!base!and!its!oxydative!derivatives,!it!is!needed!to!characterize!the!proteins!which!interact!with!this!pattern.!
!!!
!!
!The!identification!and!the!characterisation!of!these!proteins!should!give!us!a!better!insight!regarding!
this! epigenetic! mecanisms! and! therefore! could! reveal! new! therapeutic! targets.! Recent! studies! have! be!realised!in!the!field(3)!and,!subsequently!we!propose!here!a!photolabeling!strategy!to!seek!to!spot!new!protein!partners.!!
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Aknowledgment:!Programme!Interface!pour!le!vivant,!UPMC!! !
Page 30
Journées)de)Chimie)Moléculaire)2016! Ourania!MAKRYGENNI!!
Hybrid!Polyoxometalates!for!homogeneous!supported!catalysis!
[email protected] !!PhD!advisor:!Richard!Villanneau!
Laboratory:)EfPOM,)4)Place)Jussieu)75252)
!Polyoxometalates! (POMs)! are! nanoscopic! clusters! consisting! of! metal! ions! in! their! highest! oxidation!
number! (WVI, MoVI, VV) assembled by O2- ligands.! Due! to! their! strong! acidity! (in! their! acidic! form)! and!favorable!redox!properties,!POMs!and!their!derivatives!have!been!used!in!homogeneous!organic!synthesis!and!catalytic!reactions!as!acid!and!oxidation!catalysts.!Meanwhile,!their!applications!as!catalyst!supports!for!transition!metal! active! species! have! also!been!explored! and! good! reusability! could!be! realized!by! taking!advantage!of!their!large!framework.!
However,!these!homogeneous!systems!have!major!limitations!related!to!separation!issues:!loss!of!active!centers,!pollution!of!products!and!incompatibility!with!processes!in!pharmacology.!Therefore,!it!is!possible!to!prepare!heterogeneous!analogues!of! the!most!commonly!used!soluble!and!homogeneous!catalysts!by!their! immobilization!on! various! insoluble! supports. The!heterogenization!of! soluble! catalysts! can! lead! to!improved!robustness!and!therefore! increased!efficiency,!as! long!as!the!dispersion!and!accessibility!of!the!active!sites!on!the!support!are!optimized.!
Thus,!two!strategies!were!chosen!for!the!heterogenization!of!POMs:!•! The!use!of!platforms!with!large!specific!area!for!the!anchorage!and!with!porosity!ranging!from!5!to!
20nm,!such!as!structured!mesoporous!materials!(Silica!type!SBA15)!•! The!use!of!core!shell!nanoparticles,!consisting!of!a!magnetic!core!(maghemite)!and!a!silica!shell.1!The!
recovery!of!the!catalyst!can!be!easily!performed!magnetically!with!a!simple!magnet.!!These! two! supports! can! be! easily! functionalized! with! reactive! organic! functions! (carboxylic! acids,!
amines)!allowing!them!to!covalently!graft!the!catalysts.2!The!synthesized!materials!were!tested!in!targeted!model!catalytic!reactions,!such!as!the!epoxidation!of!
cyclic!alkenes!from!environmentally!friendly!oxidant!(air,!O2!or!failing!H2O2).3!
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Image!1:!POMs!grafted!on!mesoporous!silica!(left)!and!magnetic!nanoparticles!(right).!!
Acknowledgment:!Work!supported!by!“Ministère!de!l’éducation!nationale,!de!l’enseignement!supérieur!et!de!la!recherche”!! !
1 T. Georgelin, V. Maurice, B. Malezieux, J-M. Siaugue, V. Cabuil, J Nanopart Res. 2010, 12, 675-680 2 R. Villanneau, A. Marzouk, Y. Wang, A. Ben Djamaa, G. Laugel, A. Proust, F. Launay, Inorg. Chem. 2013, 52, 2958-
2965. 3 F. Bentaleb, O. Makrygenni, D. Brouri, C-C. Diogo, A. Mehdi, A. Proust, F. Launay, R. Villanneau, Inorg. Chem.
2015, 54 (15), 7607–7616.
Page 31
Journées)de)Chimie)Moléculaire)2016! Juan!Ramón!JIMÉNEZRGALLEGO !
Switchable!redox!active!Fe/Co!cyanide!molecular!cube!encapsulating!K+!or!Cs+!
e,mail:[email protected] !PhD!advisor(s):!Pr.!Rodrigue!Lescouëzec!and!Dr.!Laurent!Lisnard!
Adresse:))Institut)Parisien)de)Chimie)Moléculaire)–)CNRS)UMR)8232,)UPMCfParis)6,)Sorbonne)Universités,)Ff75252,)Paris)cedex)05,)France.)Equipe)de)Recherche)en)Magnétisme)Moléculaire)et)Spectroscopie)
(ERMMES)))
In! 1996! Sato!et! al.1! described! the! first! photoinduced!magnetic!material,! K0.2Co1.4[Fe(CN)6]r6.9H2O,! in!which!an!Electron!Transfer!Coupled!to!a!Spin!Transition!(ETCST)!converts!the!diamagnetic!{FeIILSRCNRCoIII
LS}!pairs!into!paramagnetic!{FeIIILSRCNRCoII
HS}!ones!(LS:!low!spin,!HS:!high!spin)!under!light!irradiation.!The!physical!properties! of! this! 3D! inorganic! polymer,! known! as! Fe/Co! Prussian! Blue! analogues! (PBAs),! are! highly!dependent!on!their!chemical!composition!and!especially!on!the!amount!and!the!nature!of!the!inserted!alkali!ions2.!!
!
In!recent!years,!intense!research!efforts!have!been!devoted!to!the!synthesis!of!low!dimensional!models!(2D,!1D!or!0D)!of!the!Fe/Co!PBAs!in!order!to!develop!new!discrete!switchable!materials!that!can!be!easily!manipulated! and! studied3.! In! particular,! the! synthesis! of! elementary! units! of! the! PBA!network! has! been!attracting! much! interest! due! to! their! potential! magnetic! and! encapsulation! properties! and! multiredox!behaviour4.!!!
In!the!present!work,!we!will!describe!the!synthesis!and!structure!of!a!novel!octametallic!A⊂{Fe4Co4}!(A=!K+!or!Cs+)!cyanide!molecular!cube.!We!have!investigated!these!compounds!both!in!solution!and!in!the!solid!state.!Electrochemical!and!paramagnetic!NMR!reveal!the!stability!of!the!cube!in!solution!as!well!as!its!multi,redox! behaviour.!Magnetic! studies! have! shown! that! the! cubes! behave! as! switchable! units! and! as! field,induced!molecular!magnets.!!!
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1 Sato, O.; Iyoda, T.; Fujishima, A.; Hashimoto, K. Science 1996, 272, 704-705. 2 Cafun, G. Champion, M.-A. Arrio, C. C. dit Moulin and A. Bleuzen, J.Am.Chem.Soc. 2010, 132, 11552-11559.!3 R. Lescouëzec, L. M. Toma, J. Vaissermann, M. Verdaguer, F. S. Delgado, C. Ruiz-Pérez, F. Lloret and M. Julve,
Coord. Chem. Rev 2005, 249, 2691.!4 Boyer, J-L. Kuhlman, M-L. Rauchfuss, T-B. Accounts of Chemical Research 2007, 40, 233-242. D.-F. Li, R. Clérac,
O. Roubeau, E. Harté,C. Mathonière, R. Le Bris and S. M. Holmes, J. Am. Chem. Soc., 2008, 130, 252
Page 32
Journées)de)Chimie)Moléculaire)2016! Emilie!MATHIEU!!
Antioxidant!manganese!complexes:!!
Investigation!of!their!activity!and!subRcellular!location.!emilie.mathieu@ens.fr!
PhD!advisor(s):!Clotilde!Policar,!Nicolas!Delsuc!Laboratory:)Laboratoire)des)Biomolécules,)24)rue)Lhomond,)75005)Paris)
!
Oxidative!stress!has!been!identified!as!an!important!event!implicated!in!several!diseases!ranging!from!inflammatory! diseases! to! neurodegeneration! or! cancer.! SuperOxide! Dismutases! (SOD)! are! a! family! of!metallo,enzymes! implicated! in! the! reduction! of! oxidative! stress! and! inflammation! process! by! tightly!controlling! the! concentration! of! superoxide! in! cells.! In! patients!with! Inflammatory!Bowel!Diseases! (IBD),!these!enzymes!are!either!overproduced!in!an!inactive!form!or!overwhelmed.1!Thus,!the!therapeutic!use!of!purified!SOD!has!been!envisioned!but!is!limited!by!a!poor!cell!penetration!of!the!enzyme,!and!immunogenicity!problems.!To!overcome!these!drawbacks!small!complexes!mimicking!the!activity!of!SODs!have!been!designed!and!their!activity!have!been!studied!on!models!ranging!from!prokaryotic!cells!to!mices.2,3!The!challenge!is!now!to!understand!at!the!molecular!scale!their!mechanism!of!action!in!cells,!and!thus!to!answer!the!question!of!the!bioavailability!of!such!complexes.!
!!!!!!
!! In!our!group,!MnII,complex!mimicking! the!activity!of!SODs!are!designed!and!studied!on!a!cellular!model!of!IBD.!The!complex!1!have!demonstrated!a!good!SOD!activity!in)vitro)(Figure!1).4!In!this!work,!1!has!been!studied!in!a!cellular!environment.!Its!speciation,!its!location!and!its!activity!have!been!investigated!in!details.!1!exerts!an!intracellular!anti,inflammatory!activity,!as!demonstrated!by!looking!at!different!markers!of!inflammation!(IL8!and!COX2)!using!biochemistry!techniques.!Its!quantification!by!EPR!in!cell!lysates,!and!the!determination!of!its!location!using!spatially!resolved!X,ray!fluorescence,!are!correlated!with!its!activity.!These!results!led!to!the!design!of!new!derivatives!bearing!either!cell!penetrating!peptides!(CPP)!to!enhance!cellular! internalization! or! mitochondria! penetrating! peptides! (MPP),! to! accumulate! the! complex! in!mitochondria!where!the!superoxide!is!mostly!generated.5!!
!
Aknowledgment:!ENS,!CNRS!(UMR7203),!UPMC,!ANR,!PSL,!are!acknowledged!for!financial!support.!ENS,Cachan!is!gratefully!acknowledged!for!E.M.’s!fellowship.!We!thank!TGE!RENARD!(FR!3443,!CNRS)!and!UMR8601!for!access!to!the!EPR!spectrometer!for!the!EPR!experiments!and!Dr.!Boucher!for!useful!discussions,!Institut!Curie!(Orsay)!for!free!access!to!cryofixation!and!freeze,drying!facility!and!Dr.!Guerquin,Kern!and!Dr.!Marco!for!useful!discussions!and!help!in!sample!preparation,!and!APS!committee!for!beamtime.!! !
1 D. Salvemini, C. Muscoli, D. P. Miley, S. Cuzzocrea, Pulmonary Pharmacology and Therapeutics, 2002, 15, 439-447. 2 O. Iranzo, Bioinorganic Chemistry, 2011, 39, 73-8 3 I. Batinic-Haberle, A. Tovmasyan, E.R.H. Roberts, Z. Vujaskovic, K.W. Leong, I. Spasojevic, Antiox. Redox. Sign.,
2014, 20, 2372-2415 4 A.-S. Bernard, C. Giroud, H. Y. V. Ching, A. Meunier, V. Ambike, C. Amatore, M. Guille Collignon, F. Lemaître, C.
Policar, Dalton Trans., 2012, 41, 6399-6403 5 H.Y.V. Ching, I. Kenkel, N. Delsuc, E. Mathieu, I. Ivanović-Burmazović, C. Policar, J. Inorg. Biochem, 2016,
10.1016/j.jinorgbio.2016.01.025
Figure*1.*Parent"complex"1,"and"cell"penetrating"peptides"(CPP)"or"mitochondria"penetrating"peptides"(MPP)"derivatives"
"
N NN
N
NNO
MnII
+
CPP or MPP
N NHN
N
NNO
MnII
+
1
Page 33
Journées)de)Chimie)Moléculaire)2016! Emmanuel!PUIG!!
Novel!class!of!Pt(II)!metallocages!:!Design!and!selfRassembly!
[email protected] !PhD!advisors:!Christophe!Desmarets!and!Hani!Amouri!!
Laboratory:)Institut)Parisien)de)Chimie)Moléculaire,)Equipe)ARChitecture)moléculaire))
!The!design!and!construction!of!discrete!metal,organic!architectures!such!as!metal,organic!polyhedra,!
cages,!bowls!or!capsules!continue!to!attract!attention![1]!because!of!their!potential!applications!as!containers!for!storage,!recognition,!delivery!and!catalysis.![2]!The!combination!of!Pd(II)!metal!centers!associated!by!self,assembly!with!highly!directional!bridging!pyridyl!ligands!have!proved!successful!and!reliable!approach!for!the!construction!of!these!tridimensional!cages!structures.!However,!the!formation!of!platinum!nanocages!and!especially!of!type!Pt2L4!remains!relatively!scarce.![3]!
In!this!context,!our!group!have!recently!described!the!use!of!rigid!bis(ethynylpyridine)!based!ligands!which!lead!to!Pd2L4!luminescent!nanocapsules.[4]!This!nanocages!displayed!two!complementary!effects!that!operate!in!synergy!for!the!encapsulation!of!a!kinetically!labile!metal!complex![Pt(NO2)4]2,.!Our!approach!relies!on!the!use!in!a!cooperative!manner:!unsaturated!metal!center!and!assembling!ligands!displaying!endohedral!functionality!for!guest!encapsulation.!
In!this!work,!functionalized!bis(ethynylpyridine)aniline!based!bidentate!ligands,!have!been!prepared!and!fully!characterized.!They!allow!the!construction!of!a!novel!family!of!platinum!metallocages.!(Figure!1)!
Figure 1: Platinum-based metallocages!
! !
1 a) J. W. Steed and J. L. Atwood, Supramolecular Chemistry, Wiley, Chichester, 2000, b) J.-M. Lehn, Supramolecular
Chemistry, Concept and Perspectives, VCH, Weinheim, 1995. 2 a) J. J. Henkelis, M. J. Hardie Chem. Commun. 2015, 11929. b) L. Li, D. J. Fanna, N. D. Shepherd, L. F. Lindoy, F. Li
J. Inc. Phe. Mac. Chem. 2015, 82, 3. c) S. Goeb, D. Canevet, M. Salle Org. Synth. Mol. Engineering 2014, 213. d) L. Adrienssens, P. Ballester Chem. Soc. Rev. 2013, 42, 3261. e) M. M. J. Smulders, I. A. Riddell, C. Browne, J. R. Nitschke Chem. Soc. Rev. 2013, 42, 1728. f) H. Amouri, C. Desmarets, J. Moussa Chem. Rev. 2012, 112, 2015. g) D. Ajami, J. Rebek Top. Curr. Chem. 2012, 319, 57. h) T. Murase, Y. Nishijima, M. Fujita J. Am. Chem. Soc. 2012, 134, 162. i) Z. Laughera, B. C. Gibbs Chem Soc. Rev. 2011, 40, 363.
3 a) Ahmedova, A.; Momekova, D.; Yamashina, M.; Shestakova, P.; Momekov, G.; Akita, M.; Yoshizawa, M. Chem. - An Asian J. 2016, 11 (4), 474–477, b) Clever, G. H.; Kawamura, W.; Tashiro, S.; Shiro, M.; Shionoya, M. Angew. Chemie Int. Ed. 2012, 51 (11), 2606–2609, c) Clever, G. H.; Shionoya, M. Chem. - A Eur. J. 2010, 16 (39), 11792–11796, d) Liao, P.; Langloss, B. W.; Johnson, A. M.; Knudsen, E. R.; Tham, F. S.; Julian, R. R.; Hooley, R. J. Chem. Commun. 2010, 46 (27), 4932.
4 a) C. Desmarets, G. Gontard, A. L. Cooksy, M;-N. Rager, H. Amouri, Inorg. Chem. 2014, 53, 4587. b) C. Desmarets, T. Ducarre; M;-N. Rager, G. Gontard, H. Amouri, Materials 2014, 7, 287.
Page 34
Journées)de)Chimie)Moléculaire)2016! Florence!HIAULT!!
Synthesis!of!αRamino!βRhydroxy!acids!!Biocatalytic!aldolization!and!kinetic!resolution!of!1,2Rdiols!
[email protected] !
PhD!advisors:!Pr.!Janine!COSSY,!Dr.!Christophe!MEYER!Laboratoire)de)Chimie)Organique,)Institute)of)Chemistry,)Biology)and)Innovation)(CBI),)
ESPCI)Paris,)CNRS)(UMR8231),)PSL*)Research)University,))10)rue)Vauquelin,)75231)Paris)Cedex)05,)France)
!Optically!active!α,amino!β,hydroxy!acids!are!encountered!in!several!natural!or!synthetic!compounds!
exhibiting! interesting!bioactivities.1,2!Among! the!different!possible!strategies! for! their! synthesis,! the!aldol!condensation!between!glycine!derivatives!and!aldehydes!represents!one!of!the!most!direct!entry!towards!α,amino!β,hydroxy!acids.2!However,!use!of!protecting!groups! is!often! required.!On! the!contrary,! threonine!aldolases!are!able!to!catalyze!such!aldol!condensations!using!unprotected!glycine,!with!an!excellent!control!of!the!amino,substituted!stereocenter!(α!position)!but!with!moderate!diastereoselectivity!with!respect!to!the! hydroxy,substituted! β! position.3! We! have! examined! the! substrate! scope! of! this! biocatalyst! for! the!synthesis!of!various!α,amino!β,hydroxy!acids.!
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!!In!addition,!α,β,dihydroxy!esters!can!be!used!as!precursors!of!α,amino!β,hydroxy!acids!possessing!a!
quaternary!stereocenter!at!the!α!position.4!The!synthesis!of!these!latter!dihydroxyesters!was!achieved!with!very!high!enantiomeric!purities!by!a!lipase,mediated!kinetic!resolution!of!the!racemic!by!monoacetylation.!
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Acknowledgment:!Financial!support!from!Protéus/PCAS!(CIFRE!grant)!is!acknowledged.! !
1 (a) K. Li, G. Tan, J. Huang, F. Song, J. You, Angew. Chem. Int. Ed. 2013, 52, 12942. (b) W. Lee, J.-H. Youn, S. H.
Kang, Chem. Commun. 2013, 49, 5231. 2 Y. Zhang, H. Farrants, X. Li, Chem Asian J. 2014, 9, 1753-1764. 3 N. Dückers, K. Baer, S. Simon, H. Gröger, W. Hummel, Appl. Microbiol. Biotechnol. 2010, 88, 409-424. 4 H. Shao, Q. Zhu, M. Goodman, J. Org. Chem. 1998, 63, 5240-5244.
Page 35
Journées)de)Chimie)Moléculaire)2016! Laurine!Gonnard!!
MetalRcatalyzed!arylation!of!piperidines!!
[email protected] !PhD!advisor(s):!Dr.!Amandine!Guérinot!and!Pr.!Janine!Cossy!
Laboratoire)de)Chimie)Organique,)Institute)of)Chemistry,)Biology)and)Innovation)(CBI)fUMR)8231)
ESPCI)Paris,)CNRS,)PSL*)Research)University,)10)Rue)Vauquelin)75231)Paris)Cedex)05,)France,!!
N,Heterocycles! such! as! piperidines! are! important! moieties! present! in! natural! and! synthetic!compounds!and!are!known!for!their! interesting!biological!properties.1!Since!piperidine!is!one!of!the!most!commonly!used!heterocycle!in!medicinal!chemistry,!2!the!development!of!new!and!efficient!methods!for!its!functionalization! is! of! great! interest.! In! particular,! the!direct! arylation!of! 4,! and!3,halogenopiperidine!by!cross,coupling!reaction,!using!cheap!and!non,toxic!complexes,!appears!to!be!a!powerful!strategy.!Moreover,!very!few!examples!of!metal,catalyzed!cross,couplings!applied!to!3,halogenopiperidines!have!been!reported!in!the!literature.3!!
For! our! part,! we! have! developed! a! cobalt,based! catalytic! system! allowing! the! efficient! and!convenient!cross,coupling!between!4,!and!3,iodo,piperidine!and!aryl!or!(hetero)aryl!Grignard!reagents.4!
!
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For! the! C2! functionalization! of! piperidines,! a! different! strategy! implying! directed! ruthenium,catalyzed!sp3!C,H!activation!has!then!been!considered!to!access!2,arylpiperidines.!According!to!pioneering!work! developed! by!Maes!et) al.5! and! Schnürch) et) al.6,! the! real! challenge! relies! on! the! development! of! a!selective!mono,arylation!procedure.!Taking!up!this!challenge,!investigations!are!currently!under!way!to!study!the!effect!of!substituted!pyridines!as!directing!groups.!!!
1 D. O’Hagan,!Nat. Prod. Rep. 2000, 17, 435–446!2 R. D. Taylor, M. MacCoss, A. D. G. Lawson, J. Med. Chem. 2014, 57, 5845-5859 3 G. A. Molander, K. M. Traister, B. T. O’Neill, J. Org. Chem., 2014, 79, 5771–5780 4 a) B. Barré, L. Gonnard, R. Campagne, S. Reymond, J. Marin, P. Ciapetti, M. Brellier, A. Guérinot, J. Cossy, Org. Lett.
2014, 16, 6160-6163 b) L. Gonnard, A. Guérinot, J. Cossy, Chem. Eur. J. 2015, 21, 12797-12803 5 A. Peschiulli, V. Smout, T. E. Storr, E. A. Mitchell, Z. Elias, W. Herrebout, D. Berthelot, L. Meerpoel, B. U. W. Maes,
Chem. Eur. J. 2013, 19, 10378-10387 6 M. C. Schwarz, N. Dastbaravardeh, K. Kirchner, M. Schnürch, M. D. Mihovilovic, Monastch. Chem. 2013, 144, 539-
552
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Journées)de)Chimie)Moléculaire)2016! Caleb!Medena!!
Helicenes:!Synthesis!and!application!in!catalysis!
[email protected] !PhD!advisors:!Pr.!Corinne!Aubert,!Dr.!Marion!Barbazanges!
Laboratory:)Institut)Parisien)de)Chimie)Moléculaire,)UMR)8232)
IPCM,)4)place)Jussieu)75252,)CC229,)Paris)cedex)05)
)Helicenes!are!polycyclic!aromatic!compounds!comprised!of!ortho,fused!benzene!rings,!which!adopt!
a!helical!configuration.!They!possess!a!series!of!interesting!chiral,!physical,!electronic!and!optical!properties.!!Helicenes!are!used!in!several!fields,!for!examples!as!chiral!ligands!or!auxiliaries!in!the!asymmetric!synthesis.1!!! We! will! present! the! synthesis! of! [6],carbohelicene! 1! by! intramolecular! [2+2+2]! cycloaddition!reaction2!of!triyne!2!and!photocyclisation!reaction3!of!distilbene!3.!!!!
!!
The!use!of!helical!gold!complex!4!in!enynes!cycloisomerization!reaction!will!also!be!disclosed.!!
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Aknowledgment:!ANR!HELICATS!(ANR,13,JS07,0013).
1 (a) Y. Shen, C.-F.Chen, Chem. Soc. Rev. 2012, 112, 1463; (b) M. Gingras, Chem. Soc. Rev. 2013, 42, 958; (c) M.
Gingras, G. Félix, R. Peresutti, chem. Soc. Rev. 2013, 42, 1007; (d) M. Gingras, Chem. Soc. Rev. 2013, 42, 1051. (e) M. Gingras, Chem Soc Rev.!2013. 42, 968; (f) Y. Shen, C. F. Chen, Chem. Rev. 2012, 112, 1463; (g) M. Gingras, G. Félix, R. Peresutti, Chem. Soc. Rev. 2013, 42, 1007; (i) P. Aillard, A. Voituriez, A. Marinetti. Dalton Trans 2014, 43, 15263-78; (j) J. Maurice, N. Takenaka, Eur. J. Org. Chem. 2014, 21.
2 F. Teplý, I. G. Stará, I. Starý, A. Kollárovic, Daniel Lustinec,, Z. Krausová, D. Saman, P. Fiedler, Eur. J. Org. Chem. 2007, 4244.
3 C. Wachsmann, E. Weber, M Czugler, W. Seichter, Eur. J. Org. Chem. 2003, 2863
MeO
MeO
MeO
MeO
OMe OMe1) [2+2+2] Cycloaddition2) Aromatization
Photocyclisation
(±)1 32
reaction
XR1
R2
R3R4
X
R2R4
R1R3
4 (2 %mol)AgSbF6 (5 %mol)
CH2Cl2
O
O
(±)
P
PAuPh Ph
Ph Ph
AuCl
Cl
4