16th Conference of the Doctoral School

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Ecole Doctorale de Chimie Moléculaire de Paris Centre - ED 406 - Director: Prof. Anna Proust
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Program of the
16 Conference of the Doctoral School
th
Amphitheatre Herpin
Monday,
May 23, 2016
morning sessions
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
Moderator
Prof. Anna Proust
Cationic niobium as a new catalytic system for hydro-functionalization
of C‒C multiple bonds
10h15 – 10h30
Maxime Laugeois
Synergistic Pd(0)/amine catalysis: a powerful tool for the asymmetric
formal [3+2] cycloaddition of vinyl cyclopropanes with enals
Coffee break
10h30 – 11h00
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
Dr. Maxime Vitale
Christophe Lévêque
Development of a versatile approach for the generation of alkyl
radicals by photooxidation of alkylsilicates
11h45 – 12h00
Fei Ye
Solvent-free ruthenium trichloride-mediated [2 + 2 + 2] Cycloaddition:
an efficient access toward fluorenone derivatives
12h00 – 14h00
Lunch
Monday,
May 23, 2016
14h00 – 14h15
afternoon sessions
Moderator
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
14h45 – 15h00
Dr. Marion
Barbazanges
Thomas Aubineau
Formation of N-containing heterocycles
Coffee break
15h00 – 15h30
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
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
Dr. Cyril Ollivier
Tuesday,
May 24, 2016
morning sessions
8h45 – 9h45
Prof. William B. Motherwell
The measurement of noncovalent functional group interactions with π
clouds using designed molecular balances.
9h45 – 10h00
Pascal Matton
Moderator
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
10h15 – 10h30
Sébastien Cardon
Quantification of the internalization efficacy of homeoproteins and
derived-cell penetrating domains
Coffee break
10h30 – 11h00
11h00 – 11h15
Prof. Matthieu
Sollogoub
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
11h45 – 12h00
Frédéric Thiebaut
Identification of rare DNA base protein partner using photolabeling
and mass spectrometry
12h00 – 14h00
Lunch
Dr. Sébastien
Blanchard
Tuesday,
May 24, 2016
14h00 – 14h15
afternoon sessions
Moderator
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
Dr. Guillaume Vives
Antioxidant manganese complexes:
Investigation of their activity and sub-cellular location.
14h45 – 15h00
Emmanuel Puig
Novel class of Pt(II) metallocages : design and self-assembly
Coffee break
15h00 – 15h30
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
16h15 – 17h15
Prof. Maurizio Prato
Novel Functional Materials from Nanocarbons to Perylene Bisimides
Prof. Giovanni Poli
Journées)de)Chimie)Moléculaire)2016!
Michel!ETIENNE!
Distorsions!CC!agostiques!et!le!ligand!cyclopropyle!:!expérience,!théorie,!réactivité!
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michel.etienne@lcc,toulouse.fr!
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Laboratoire)de)Chimie)de)Coordination)du)CNRS)et)Université)Toulouse)III)–)Paul)Sabatier,)205)route)de)Narbonne,)
BP)99044,)31077)Toulouse)Cedex)4.)
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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.!
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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.!
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“Intramolecular C–C Agostic Complexes: C–C Sigma Interactions by Another Name”. M. Etienne, A. S. Weller,
Chem. Soc. Rev. 2014, 43, 242-259.
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)
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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!
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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!
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!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!
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Acknowledgments:!ANR,!SATT!IDF!Innov!as!well!as!Labex!MiChem!are!gratefully!acknowledged!for!funding.!
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1
S. Drouet, C. Costentin, M. Robert, J-M. Savéant, Science, 2012, 338, 90.
C. Costentin, M. Robert, J-M. Savéant, Chem. Soc. Rev., 2013, 42, 2423.
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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.
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C. Costentin, M. Robert, J-M. Savéant, Acc. Chem. Res., 2015, 48, 2996.
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C. Costentin, G. Passard, M. Robert, J-M. Savéant, PNAS, 2014, 111, 14990.
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J. Bonin, M. Robert, M. Routier, J. Am. Chem. Soc., 2014, 136, 16768.
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M. Robert et al., submitted.
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C. Costentin, M. Robert, J-M. Savéant, A. Tatin, PNAS, 2015, 112, 6882.
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A. Maurin, M. Robert, J. Am. Chem. Soc., 2016, 138, 2492.
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M. Robert et al., PNAS, 2016, in press.
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William!Motherwell,!FRS,!FRSE.!
The!Measurement!of!Noncovalent!Functional!Group!Interactions!with!π!Clouds!
using!designed!Molecular!Balances.!
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[email protected]!
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Christopher)Ingold)Laboratory,)Department)of)Chemistry,)University)College)London,)20,)Gordon)St.,)London,)
WC1HOAJ.))UK.)
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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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Maurizio!Prato!
Novel!Functional!Materials!from!Nanocarbons!to!Perylene!Bisimides!
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[email protected]!
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Dipartimento)di)Scienze)Chimiche)e)Farmaceutiche,)Università)degli)Studi)di)Trieste,)Piazzale)Europa)1,)34127)Trieste,)
Italy)and)CIC)BiomaGUNE,)San)Sebastian,)Spain)
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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!
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Laura!FERRAND!
Cationic!niobium!as!a!new!catalytic!system!for!hydroRfunctionalization!of!C‒C!
multiple!bonds!
[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)
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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!
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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!
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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!
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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.!
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Access)to)tetrahydrofuran,)tetrahydropyran,)pyrrolidine,)lactam,)lactone…)
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Aknowledgment:!We!wish!to!acknowledge!the!Ministère!de!l’Enseignement!Supérieur!et!de!la!Recherche.!
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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.
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S. Arai, Y. Sudo, A. Nishida, Tetrahedron 2005, 61, 4639‒4642.
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N. T. Patil, R. D. Kavthe, V. S. Shinde, Tetrahedron 2012, 68, 8079‒8146.
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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)
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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!
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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!
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Aknowledgment:!MESR!
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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.
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(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, 23352338; (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, 150153.
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For a recent review, see: S. M. Inamdar, V. S. Shinde and N. T. Patil, Org. Biomol. Chem., 2015, 13, 8116-8162.
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M. Laugeois, S. Ponra, V. Ratovelomanana-Vidal, V. Michelet and M. R. Vitale, Chem. Commun., 2016, 52, 53325335.
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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)
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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.!
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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).!
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O
X
Rh
O
X
DG
H
(X = O, N, S)
R
additive, solvent, T
25 examples
up to 93% yield
Gram-Scale
Mild conditions
O
X
DG
R
al
ov roup
m
Re ing G
t
ec
Dir
C−O bond
cleavage
Cr
os
s-c
ou
pli
ng
R
H
X
R
Ar
X
R
Scheme!1.!
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We! will! present! and! discuss! the! scope! and! limitations! of! this! method! as! well! as! various! post,
functionalizations.!
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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.
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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.
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(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.
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Schröder, N.; Lied, F.; Glorius, F. J. Am. Chem. Soc. 2015, 137, 1448.
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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
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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!H22!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.!
!
!
!
!
!
!
!
1
!
!
Jenny S. J. McCahill, Gregory C. Welch, and Douglas W. Stephan, Angew. Chem. Int. Ed., 2007, 46, 4968-4971
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!
2
!
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.
!
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!derivatives !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!
!
O
O
R1
!
R3
RuCl 3 · nH 2O 5 mol%
!
R3
1
R
no solvent
!
50 to 80 °C, 2-18 h
R3
R3
R2
R2
!
(2 eq.)
18 examples
up to 81% yield
!
!
!
! 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!
!
!
Acknowledgment:!F.!Y.!thanks!the!China!Scholarship!Council!(CSC).! !
!
1
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), WileyVCH, 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.!
!
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!!
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.!
!
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.!
!
H2"atmosphere
IZn
H"or"R'
R
O
R="Alkyl"or"Aryl
ZnI ,
ClRh(PPh3)3
Domino&Process
!
R
H"or"R'
up"to"86%
!
!
1!
2
!
"(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."
! (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.
!
!
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.!
!
!
!
!
!
!
!
Acknowledgment:!Omar!KHALED!for!HRMS,!Lise!Marie CHAMOREAU!for!XRD,!CSC!for!scholarship.!UPMC!&!
CNRS!for!financial!support.!
!
1
2
D. Basavaiah, B. S. Reddy, S. Badsara, Chem. Rev. 2010, 110, 5447.
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.
!
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!
OH
CF3
CF3
N
Bn 2'
N
Bn
CF3
2
N
Bn
(eq 1)
Nu
Nu
!
!
!
!
!
!
!
!
1
N
Bn
OH
CF3
2
N
Bn
CF3
2'
N
Bn
CF3
Nu
(eq-2)
Nu
!
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.
!
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!
!
R
NaH
Ts
N
H
H
N
1,2
N
(1 equiv)
DMF
NaH
Ts
TMS
O
N
(2 equiv)
-NR = amides, carbamates
NaH
(1 equiv)
I
O
R
1,2
Ts
TMS-EBX
R
H
N
N
1,2
TMS-EBX
R
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).!
!
Ts
N
OH
Ts
OH
R
N
FeCl3.6H2O (5 mol %)
CH2Cl2, 50 °C, 2 h
H
O
H
R
cis/trans = 90/10 to 99/1
Scheme 4!
!
!
!
!
1
!
E. Vitaku, D. T. Smith, J. T. Njardarson, J. Med. Chem. 2014, 57, 10257-10274.
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.
2
!
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.
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.
2
!
Benjamin!FLAMME!
Rational!design!of!5V!organic!electrolytes!
Benjamin.flamme@chimie,paristech.fr!
1
1
1
1,2
Mansour!HADDAD ,!Phannarath!PHANSAVATH ,!Virginie!VIDAL ,!Alexandre!CHAGNES !
1
Chimie)ParisTech,)PSL)Research)University,)CNRS,)Institut)de)Recherche)de)Chimie)Paris)(IRCP),)Ff75005)Paris,)France.)
2
Réseau)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.!
!
!
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,
Figure 1: Scheme of a long-range electron
target! solution! drop! itself! deposited! onto! a! 5! mm,diameter! gold!
transfer RNA biosensor with redox intercalator
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
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
2
!
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.!!
!
!
R1
!
!
N
N
!
NH R!! 2 HN
N
N
!
!
N
N
!
!
A:!Ru(bpy) ,!Ru(4,4’,Mebpy) !
2
2
!
B:!Co(phen) ,!Co(tpy)Cl,!Ru(bpy) ,!Ru(4,4’,Mebpy) !
2
2
2
!
t
R :!H,! Bu!
1
!
R :!H,!OH!
2
!
!
Aknowledgment:!
I!acknowledge!D.!Meyer!(DR,!ICSM)!for!providing!complexes,!and!Paris!Sciences!et!Lettres!(PSL)!Research!
University!for!financial!support.!
!
A
1
2
!
!X.!Wang,!M.!Fontecave,!et!al.,!Chem.)Soc.)Rev.!(submitted)!
!O.!Ishitani,!et!al.,!!Inorg.)Chem.,!2005,!44,!2326,2336!
B
!
Pascal!MATTON!
Glycolipid!functionalized!microdroplets!for!cells!vectorization!
[email protected]!
1
2
PhD!advisor(s):!Jean!Maurice!MALLET ,!Jacques!FATTACCIOLI !
Laboratoires)des)biomolecules,)CNRS)UMR)7203,)Department)of)Chemistry,)ENS,)24)rue)Lhomond,)Paris)75005)
2
Laboratoire)P.A.S.T.E.U.R,)CNRS)UMR)8640,)UPMC,)Department)of)Chemistry,)ENS,)24)rue)Lhomond,)Paris)75005)
)
1
!
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).!
!
Fluorescent+lec,n+
Droplet++
Fluorescent+
glycolipid++
!
!
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.
!
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.
!
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!
!
!
!
!
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.
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.
2
!
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.!!
!
!
A Ca CaM:FKBP52
B
!
1:0
G113
Ca CaM:FKBP52
1:1
N-ter
!
V55
C-ter
!
M145
!
F19
M109
!
M71
!
!
A147
!
hydrophobic
pockets
A57
!
(1H) [ppm]
!
! D
C 0,9
!
0,8
Methionine methyl groups of Ca4CaM
!
0,7
0,6
!
Synthetic!FKBP52+derived!Calmodulin!binding!peptide!!
0,5
!
0,4
!
0,3
Aknowledgments:!LBM!team!1:!Yves!Jacquot,!Cillian!Byrne,!Caroline!Bushdid,!LBM!team!3:!!Ludovic!Carlier,!
0,2
Institut!Professeur!Baulieu:!E.E.!Baulieu,!Béatrice!Chambraud,!IBPS:!Gérard!Bolbach,!Emmanuelle!Sachon,!
0,1
Ca CaM:FKBP52
1:0
Gilles!Clodic,!Lucrèce!Matheron,!IBBMC:!Michel!Desmadril,!Magalie!Nicaise,!INSA:!Guy!Lippens!
0,0
Ca CaM:FKBP52
1:1
0 10 20 30 40 50 60 70 80 90 100 110 120 130 140
!
!
Residue number
(1H) [ppm]
4
{278-300}
{278-300}
(13C) [ppm]
amide CSP [ppm]
(15N) [ppm]
4
4
4
1
A.Kamah et al, J. Mol. Biol., 2016
J. Giustiniani et al., The FASEB Journal, 2015,29
3
O’Day, Journal of Alzheimer’s disease, 2015, 46, 553-569
2
{278-300}
{278-300}
!
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
2
B. Sumer, J. Gao, Nanomedicine, 2008, 3, 137-140
G. Béalle, R. Di Corato, J. Kolosnjaj-Tabi, V. Dupuis, O. Clément, F. Gazeau, C. Wihelm, C. Ménager, Langmuir,
2012, 28, 11834-11842.
!
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.!
!
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!
!
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.!
!
!
!
!
!
!
Aknowledgment:!Programme!Interface!pour!le!vivant,!UPMC!
!
!
!
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
R. Villanneau, A. Marzouk, Y. Wang, A. Ben Djamaa, G. Laugel, A. Proust, F. Launay, Inorg. Chem. 2013, 52, 29582965.
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.
2
!
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!{FeIILSRCNRCoIIILS}!
pairs!into!paramagnetic!{FeIIILSRCNRCoIIHS}!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.
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.!
2
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
Emilie!MATHIEU!
!
Antioxidant!manganese!complexes:!!
Investigation!of!their!activity!and!subRcellular!location.!
[email protected]!
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.!
+
+
!
O
O
!
N
N
N
Mn II
N
Mn II
N
N
N
!
N
N
NH
N
N
CPP or MPP
!
1
!
Figure*1.*Parent"complex"1,"and"cell"penetrating"peptides"(CPP)"or"mitochondria"penetrating"
!
peptides"(MPP)"derivatives"
!
"
!
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.
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
2
!
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.
!
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.!
!
!
!
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.
!
!
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!
!
!
!
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!
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, 539552
2
!
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.!!
!
!
MeO
OMe
Photocyclisation
reaction
1) [2+2+2] Cycloaddition
2) Aromatization
MeO
OMe
MeO
MeO
(±)
1
2
3
!
The!use!of!helical!gold!complex!4!in!enynes!cycloisomerization!reaction!will!also!be!disclosed.!
!
!
R1
X
4 (2 %mol)
AgSbF6 (5 %mol)
R2
R4
X
CH2Cl2
R3
Ph
Cl
Cl
Au
Au
Ph
R2
R1
R3
R4
!
Ph
P
O
P
O
Ph
4
!
!
(±)
!
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
!

16th Conference of the Doctoral School

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