Journées de Chimie Moléculaire 2011 by panniuniu

VIEWS: 63 PAGES: 42

									 




                                                            
                                                     
              Journées de Chimie Moléculaire 2011 
                                
 
Lundi 23 Mai 2011                                 Amphi Herpin, Bâtiment Esclangon   
 
9h00–9h15         Présentation de la nouvelle équipe de direction de l’ED406 
                  Introduction des Journées de Chimie Moléculaire  
                  Pr.  Anna  PROUST,  directrice  de  l’ED406  et  Pr.  Matthieu  SOLLOGOUB,  directeur 
                  adjoint 
 
Modérateur : Pr. Gérard JAOUEN 
 
9h15–10h15        Conférence du Professeur Stephen J. LIPPARD 
                  Massachusetts Institute of Technology, Cambridge, USA 
                  Inorganic Chemistry in Cancer Diagnosis and Treatment 
 
Modérateur : Pr. Anna PROUST 
 
10h15–10h30       Aurelie DAMAS 
                  Octahedral  Assemblies  Based  on  Quinonoïd  Organometallic  Linkers:  Design, 
                  Structure and Luminescent Properties 
 
10h30–10h45       Ségolène ADAM DE BEAUMAIS 
                  Synthesis of Dimers and Duplexes Based on Cyclodextrins 
 
10h45–11h00       Benoît RIFLADE 
                  New Functionalized Hybrid of the Dawson‐Type POM [P2V3W15O62]9‐ 
 
11h00–11h20                               PAUSE 
 
Modérateur : Dr. Corinne AUBERT 
 
11h20–11h35       Guillaume DURIEUX 
                  New Cobalt (II) Complexes for the Ring‐Opening Polymerization of Lactones 
 
11h35–11h50       Hajer ABDELKAFI 
                  Towards the Asymmetric Total Synthesis of the Norditerpene (+)‐Harringtonolide 
 
11h50–12h05       Alexandre PRADAL 
                  Electrophilic Activation of Enynes : Cycloisomerization Reactions in the Presence of 
                  Gold, Platinum Complexes or Iodonium Ions. 
 
12h05–12h20       Moslem ALAAEDDINE 
                  New Molecules of Pyrannylidenes for Photovoltaic Conversion 
 
12h20–12h35       Ljubica SVILAR 
                  Study of Nitrogenized Azaphilones from Fungi Hypoxylon Fragiforme by 
                  Electrospray and H/D Exchange Mass Spectrometry 
 
12h35–14h15                                 DEJEUNER 
 
Modérateur : Dr. Franck FERREIRA 
 
14h15–14h30        Benoît DE CARNE‐CARNAVALET 
                   Copper‐Free Sonogashira Coupling of Cyclopropyl Iodides with Terminal Alkynes 
 
14h30–14h45        Mylène AUGE 
                   Development of New Metalated‐Arene‐Phosphino Ligands and Application to Gold 
                   Chemistry 
 
14h45–15h00        Dénia MELLAL 
                   Synthesis of Analogues of Aminoacyl‐tRNAs for the Study and the Inhibition of 
                   FemX Transferase  
 
15h00–15h15        Bixue XU 
                   Synthesis of Monofluoro‐Carbasugars and gem‐Difluoro‐Carbasugars 
 
15h15–15h30        Céline HUBERT 
                   Detection of Explosives on Solid Samples by High Resolution Mass Spectrometry 
 
15h30–15h45        Viet Hung NGUYEN 
                   Concomitant EDD and EID of DNA Evidenced by MSn and Double Resonance 
                   Experiments 
 
15h45–16h05                                 PAUSE 
 
 
Modérateur : Dr. Virginie MANSUY 
 
16h05–16h20       Carine ROBERT 
                  Supported  Neodymium  Catalysts  for  Isoprene  Polymerization:  Modulation  of 
                  Reactivity by Controlled Grafting 
 
16h20–16h35       Benjamin MONTAIGNAC 
                  Combined Metal‐ and Amine‐Catalyzed Intramolecular Addition of  α‐Disubstituted 
                  Aldehydes onto Unactivated Alkynes 
 
16h35–16h50       Thomas COCHET 
                  (E)‐Dimethyl 2‐Oxopent‐3‐Enylphosphonate: An Excellent Substrate for Cross‐
                  Metathesis. An access to Functionalized Heterocycles 
 
16h50–17h05       Benjamin MATT 
                  Hybrid Polyoxometalates for Solar Energy Conversion 
 
Modérateur : Pr. Matthieu SOLLOGOUB 
 
17h05–18h05       Conférence du Professeur Jeffrey W. BODE 
                  ETH‐Zürich, Switzerland 
                  Molecular Barbapapas 
                   
Mardi 24 Mai 2011                                 Amphi Herpin, Bâtiment Esclangon   
 
9h00–9h15         Intervention du Dr. Peter REINHARDT 
                  2011 : Année Internationale de la Chimie       
 
Modérateur : Dr. Emmanuel LACÔTE 
 
9h15–10h15        Conférence du Professeur Klaus MÜLLEN 
                  Max‐Planck‐Institute for Polymer Research, Mainz, Germany 
                  From  Conjugated  Polymers  to  Graphenes  –  a  Discovery  Journey  to  Electronic 
                  Materials 
 
10h15–10h30       Carole SAUER 
                  Green and Non‐Toxic Functionalization of Metal Oxide Surfaces: Application to ITO 
 
10h30–10h45       Meihui ZHENG 
                  Design and Development of a Cathode Modified by Laccases 
 
10h45–11h00       Gilles Alex PAKORA 
                  Purification and Characterization of Secondary Metabolites of Cocoa Endophytic 
                  Fungi. Study of their Activity and their Biotransformations 
 
11h00–11h20                                PAUSE 
 
Modérateur : Dr. Sandrine SAGAN 
 
 
11h20–11h35       Aude COLON 
                  DNA‐Based Asymmetric Catalysis 
 
11h35–11h50       Florence MAUGER 
                  Development of a DNA Sequencing Method using Cleavage of RNA/DNA Chimeras 
                  and MALDI‐TOF Mass Spectrometry 
 
11h50–12h05       Ludovic HALBY 
                  Synthesis of New DNMT Inhibitors: Rapid Synthesis and In‐vitro Activity of 
                  Procainamide Derivatives 
 
12h05–12h20       Huanhuan QU 
                  Synthesis and Anticancer Activities Study of Glycosphingolipids 
 
12h20–12h35       Baiyi XUE 
                  Structural Characterization of Antibody Drug Conjugates in Animal Plasma by High 
                  Resolution Mass Spectrometry 
 
12h35–14h15                                DEJEUNER 
 
Modérateur : Dr. Julie OBLE 
 
14h15–14h30        Florent LE BOUCHER D’HEROUVILLE 
                   Strategies for the Synthesis of Atropoisomeric Diphosphines 
 
14h30–14h45        Bruno ANXIONNAT 
                   Monoalkylation of Acetonitrile Using Primary Alcohols 
 
14h45–15h00        Chérine BECHARA 
                   Role  of  Plasma  Membrane  Components  in  the  Internalization  of  Cell‐Penetrating 
                   Peptides 
 
15h00–15h15        Hugo LENORMAND 
                   Detection and Destruction of Organophosphorous Compounds by Hypervalent 
                   Stable Silylated Molecules 
 
15h15–15h30        Charlélie BENSOUSSAN 
                   Efforts Towards the Synthesis of the Fragment C30‐C52 of Amphidinol 3 
 
 
15h30–15h50                                  PAUSE 
 
Modérateur : Dr. Sylvain DARSES 
 
15h50–16h05        Mathieu CYKLINSKY 
                   Rearrangement of Acetylenic Epoxides and Aziridines 
 
16h05–16h20        Guillaume LEFEVRE 
                   First Evidence of Oxidative Addition of Fe0(N,N)2 to Aryl Halides. This Precondition 
                   is not a Guarantee of Efficient Fe‐Catalyzed C‐N Cross‐Couplings 
 
16h20–16h35        Idrissa NDOYE 
                   Isolation and Chemical Transformation of Metabolites from Paraconiothyrium 
                   Variabile, an Endophytic Fungus of Cephalotaxus Harringtonia 
 
16h35–16h50        Steven GIBOULOT 
                   Carbonylation/Carroll Rearrangement Domino Sequence Catalyzed by Palladium 
 
Modérateur : Dr. Christophe MEYER 
 
16h50–17h50        Conférence du Professeur Tomislav ROVIS 
                   Colorado State University, Fort Collins, USA 
                   Design and Utility of Chiral Carbenes for Asymmetric Umpolung 

                                               CLOTURE 
Journées de Chimie Moléculaire 2011 
23 et 24 mai 2011 
 
 
              From Conjugated Polymers to Graphenes – a Discovery Journey to 
                                                               Electronic Materials 
                                                 Klaus Müllen 
                                                        
                      Max‐Planck‐Institute for Polymer Research, Mainz, 55128, Germany 
                                                        muellen@mpip‐mainz.mpg.de 
 
 
       Research into energy technologies and electronic devices is strongly governed by the 
available  materials  which  highlights  the  role  of  synthesis.  More  recently,  carbon‐rich 
molecules  of  different  dimensionality  have  played  an  increasingly  important  role  as 
conductors,  semiconductors  and  catalysts  and  are  attractive  alternatives  to  established 
organic  and  inorganic  materials.  The  unique  physical  and  chemical  properties  of  the  two‐
dimensional  (2D)  π‐electron  system  graphene  ask  for  its  chemical  synthesis,  but  also  the 
synthesis of new conjugated polymer chains continues to define great challenges. 
        We  introduce  new  donor‐acceptor  polymers  and  we  design  a  synthetic  route  to 
graphenes which is based upon the cyclodehydrogenation (“graphitization”) of well‐defined 
dendritic  (3D)  polyphenylene  precursors.  This  approach  is  superior  to  physical  methods  of 
graphene formation. A further exciting option is the synthesis of graphene nanoribbons with 
atomic precision after immobilization of monomers on substrate surfaces. In‐situ monitoring 
of  the  reactions  by  scanning  tunneling  microscopy  holds  promise  for  a  “programmed 
polymer synthesis”. 
       Lamellar  and  columnar  superstructures  assembled  from  conjugated  polymers  (1D) 
and nanographene discs (2D), respectively, serve as charge transport channels in electronic 
devices.  Field‐effect  transistors  (FETs)  and  sensors  are  described  as  examples  and  their 
exemplary  performance  is  discussed  in  terms  of  supramolecular  order  and  optimized 
processing techniques. Exciting applications of unprecedented carbon‐rich materials are also 
shown for batteries, supercapacitors and fuel cells. 
 
 
 
Wu, J.S., Pisula, W., Müllen K., Chem. Rev. 2007, 107, (3), 717. Müllen, K., Rabe, J.R., Acc. Chem. Res. 2008, 41, (4), 511. Wang, X., Zhi, L., 
Müllen, K. Nano. Lett. 2008, 8, 323. Feng, X.; Marcon, V.; Pisula, W.; Hansen, M. R.; Kirkpatrick, J.; Andrienko, D.; Kremer, K.; Müllen, K., 
Nature Mater. 2009, 8, 421. Liu, R., Wu, D., Feng, X., Müllen, K., Angew. Chem. Int. Ed. 2010, 49, 2565. Käfer, D., Bashir, A., Dou, X., Witte, 
G., Müllen, K., Wöll, C., Adv. Mater. 2010, 22, 384. Diez‐Perez, I., Li, Z., Hihath, J., Li, J., Zhang, C., ang, X., Zang, L., Dai, Y., Heng, X., Müllen, 
K., Tao, N. Nature Commun. 2010, DOI: 10.1038. Liang, Y.; Schwab, M. G.; Zhi, L. J.; Mugnaioli, E.; Kolb, U.; Feng, X. L.; Müllen, K. J. Am. 
Chem. Soc. 2010, 132, 15030. Yang, S.; Feng, X.; Ivanovic, S.; Müllen, K. Angew. Chem. Int. Ed. 2010, 49, 8408. Yang, S.; Feng, X.; Wang, L.; 
Tang,  K.;  Maier,  J.;  Müllen,  K.  Angew.  Chem.  Int.  Ed.  2010,  49,  4795.  Cai,  J.,  Ruffieux,  P.,  Jaafar,  R.,  Bieri,  M.,  Braun,  T.,  Blankenburg,  S., 
Muoth, M., Seitsonen, A. P., Saleh, M., Feng, X., Müllen, K., Fasel, R. Nature 2010, 466, 470. Treier, M.; Pignedoli, C. A.; Laino, T.; Rieger, R.; 
Müllen, K., Passerone, D.; Fasel, R. Nature Chem. 2011, 3, 61‐67. Dietz‐Perez, I., Hihath, J., Hines, T., Wang, Z.S. Zhou, G., Müllen, K., Tao, 
N.J., Nature Nanotechnology 2011, 6, 226‐231. Tsao, H.N., Cho, D.M., Park, I., Hansen, M.R., Mavrinsky, A., Yoon, D.Y., Graf, R., Pisula, W., 
Spiess, H.W., Müllen, K., J. Am. Chem. Soc. 2011, 133, 8, 2605‐2612. 
Journées de Chimie Moléculaire 2011 
23 et 24 mai 2011 
 
 
          Design and Utility of Chiral Carbenes for Asymmetric Umpolung 
                                         Tomislav ROVIS 
                                                   
                          Colorado State University, Fort Collins, USA 
                                   rovis@lamar.colostate.edu 
 
 
       We  have  been  engaged  in  the  design  of  chiral  N‐heterocyclic  carbene  scaffolds  for 
mediating  asymmetric  organic  transformations.  In  particular,  carbenes  are  noted  for 
inverting the normal mode of reactivity of aldehydes from electrophiles into nucleophiles, a 
process termed umpolung. Early work has focused on rendering asymmetric the conjugate 
addition  of  aldehydes  into  Michael  acceptors,  the  Stetter  reaction.   Recent  work  has 
involved  developing  the  intermolecular  version  of  this  reaction  as  well  as  extending  the 
reactivity  of  these  carbenes.  Catalyst  design,  reaction  development,  mechanistic 
investigations and applications to synthesis will be discussed. 
Journées de Chimie Moléculaire 2011                                                        Ségolène ADAM de BEAUMAIS
23 et 24 mai 2011


                                 Synthesis of dimers and duplexes based on cyclodextrins
                                                      Prof. Matthieu Sollogoub, Dr. Mickaël Ménand
                                      UPMC Université Paris 6, Institut Parisien de Chimie Moléculaire, UMR CNRS 7201
                                                 Glycochimie Organique Biologique et Supramoléculaire,
                                             Bat. F, 2ème étage – 4 place Jussieu, C. 181, 75005 Paris, France
                                                          e-mail : sego.de.beaumais@hotmail.fr


Keywords: cyclodextrin, dimer, duplex, supramolecular polymer

                                                       1
           Since the ‘80s, Breslow et al. have developed dimers and duplexes based on cyclodextrins (CD). They
have shown that these structures have high association constants mimicking biological receptors. However, the
low efficiency of the synthesis of such compounds has slowed down their exploitation.
                                                                                                                                        2
           Our group has designed some flexible duplexes involved in the reticulation of biogels. These
                                                                                                                                                  3
compounds are easily available by in-house methodology allowing access to regioselective precursors.
However, the flexibility of the linker might be responsible for the random complexation behavior.
Hence, to tackle this problem, we anticipated that more rigid dimers and duplexes should rule out the self-
inclusion of the linker affording free cavities. Therefore, we developed an efficient synthetic pathway to these
architectures through an original multi-click macrocyclisation process.
               directionnality




           These compounds are part of projects in order to develop some polyrotaxanes, supramolecular
polymers, Alzheimer’s disease applications and encapsulation of lipids.


Acknowledgments/Financial assistance: Ministère de la Recherche et des Technologies

1
  Tabushi, I. ; Kuroda, Y. ; Shimokawa, K. ; J.Am.Chem.Soc. 1979, 101, 1614-1615; Breslow, R.; Halfon, S.; Zhang, B. Tetrahedron 1995, 51,
377-388; Sasaki, K.; Nagasaka, N.; Kuroda, Y. Chem.Commun. 2001, 2630-2631.
2
  Bistri, O. ; Mazeau, K., Auzély-Velty, R. ; Sollogoub, M. Chem.Eur.J. 2007, 13, 8847-8857.
3
  Pearce, A. J. ; Sinaÿ, P. Angew.Chem.Int.Ed.Engl. 2000, 39, 3610-3612 ; Lecourt, T. ; Hérault, A. ; Pearce, A. J. ; Sollogoub, M. ; Sinaÿ, P.
Chem.Eur.J. 2004, 10, 2960-2971.
Journées de Chimie Moléculaire 2011                                                                            Benoît RIFLADE
23 et 24 mai 2011



           New functionalized hybrid of the Dawson-type POM [P2V3W15O62]9-
                                                 Pr. B. Hasenknopf, Dr. E. Lacôte, Pr. S. Thorimbert
                                                                   Pr. M. Malacria
                              Institut Parisien de Chimie Moléculaire (UMR7201), Université Pierre et Marie Curie
                                                  Bât F, 2ème étage, case 229, Paris cedex 75252
                                                          e-mail : benoit.riflade@upmc.fr

Keywords: polyoxometalates, organic-inorganic hybrid composites, vanadates


Polyoxometalates (POMs) are a large family of metal-oxygen clusters of early transition metals in high oxidation
states with great catalytic applications. Functionalization of their basic structures grafting organic molecules is
                                                                                                                                         1
a way to increase the diversity of these inorganic clusters, as well as to possibly tune the catalytic activity.
We will present the grafting of diol-amides, carbamates, thiocarbamates and ureas to the Dawson
                                                  2
tungstovanadate TBA5H4[P2V3W15O62]. These transformations produce an original family of functionalized
POMs featuring an electronic communication between the ligand and the POM allowing fine-tuning of the
entire hybrid redox properties.
Moreover, using a specific pyridine ligand, we successfully synthesized a new type of late transition metal
containing POM where an indirect connection between the metal and the POM takes place through the ligand.
We will focus on the synthesis and applications of such hybrids.




Acknowledgments/Financial assistance: Université Pierre et Marie Curie, Centre National de la Recherche
Scientifique, Ministère de l'Enseignement Supérieur et de la Recherche




1
    Long D-L., Tsunashima R., Cronin L., Angew. Chem., Int. Ed. 2010, 49, 1736-1758.
2
    Li J., Huth I., Chamoreau L.–M., Hasenknopf B., Lacôte E., Thorimbert S., Malacria M., Angew. Chem., Int. Ed. 2009, 48, 2035-2038.
Journées de Chimie Moléculaire 2011                                                                            Guillaume Durieux
23 et 24 mai 2011



    New Cobalt (II) complexes for the ring-opening polymerization of lactones
                                                            Pr. Christophe THOMAS
                                                   Laboratoire Charles Friedel, UMR 7223
                                          Chimie Paristech, 11 rue Pierre et Marie Curie, 75005 Paris
                                               e-mail : guillaume-durieux@chimie-paristech.fr

Keywords: Cobalt (II) complexes, Ring-opening polymerization, biodegradable polymers


           Today, more than 99.9% of the polymer production is coming from non renewable resources like oil,
                                                                      1
leading to environmental issues when disposed. An attractive alternative is the use of biodegradable
polymers. Among these polymers, the poly-(hydroxyalkanoate)s, like poly(3-hydroxybutyrate), are a class of
          2
interest. One synthetic pathway is the ring-opening polymerization of the corresponding lactone via a
                                              3
coordination-insertion mechanism. Zinc and magnesium complexes modified by ancillary ligands have been
used with great success for the controlled polymerization of polar monomers. In particular, mononuclear Zn(II)
complexes supported by tetradentate phenoxyamine ligands have been shown to be of great utility for the
                                                                  4
ring-opening polymerization (ROP) of cyclic esters. A notable variable that has been shown to influence cyclic
ester polymerization reactivity is the nature of the metal ion in the catalytic complex. For example, studies of
the relative reactivity of mononuclear complexes with identical supporting ligands but divergent metal ions
                         2+                                               2+                              2+              2+
have shown that Co polymerizes lactide faster than Zn . Replacement of the Zn ions by Co was inspired by
                                                                                                                                5
analogous replacements performed in structure/function studies of the dizinc hydrolytic enzymes.
           The synthesis of original Co(II) complexes has been performed along with characterization
experiments. Non-routine 1H NMR experiments allowed us to understand the paramagnetic signature of our
Co (II) complexes. Different complexes have been then characterized. Preliminary investigations of the
reactivity of some of the prepared complexes toward -butyrolactone are also reported.




Acknowledgments/Financial assistance: DGA

1
  Bewa, H. Matériaux polymères biodégradables et applications, ADEME, 2006.
2
  Mecking, S. Angew. Chem. Int. Ed. 2004, 43, 1078-1085
3
  Thomas, C. M., Chem. Soc. Rev. 2010, 39, 165-173
4
  Zheng, Z. ; Zhao, G. ; Fablet, R. ; Bouyahyi, M.; Thomas, C. M.; Roisnel, T.; Casagrande Jr, O.; Carpentier, J.-F. New J. Chem. 2008, 32, 2279-
2291
5
  Breyfogle, L. E. ; Williams, C. K. ; Young Jr., V. G.; Hillmyer, M. A.; Tolman, W. B. Dalton Trans. 2006, 928-936
Journées de Chimie Moléculaire 2011                                                                                         Hajer Abdelkafi
23 et 24 mai 2011



                                   Towards the asymmetric total synthesis of
                                           the norditerpene (+)-harringtonolide
                                                    Encadrant : Dr. Bastien Nay
                                   Molécules de Communication et Adaptation des Micro-organismes
                       UMR 7245 CNRS-MNHN, Muséum National d’Histoire Naturelle, 57 rue Cuvier (CP 54), 75005 Paris
                                                      e-mail: bnay@mnhn.fr

Keywords: natural product, total synthesis, asymmetry


             Harringtonolide (6), also called hainanolide, is a complex polycyclic norditerpene first isolated in 1978
                                                                           1
from the Asian plum yew Cephalotaxus harringtonii . In addition to its biological activities (plant growth
inhibition, antiviral and antitumor activities), we were particularly attracted by its original structure. Our
strategy for this asymmetric synthesis, starting from the chiral pool (D-glucose), relies on several key steps
leading to the formation of each of the four rings (A, B, C and D) and the oxygenated ring system.


                                                                                                     Cascade
                                          CH3 Methodologies                                    CH3 cyclization             CO2Et
                         O                                                                                             H
                                    B          in progress                                         in progr ess
                              A    O        O                                  Br O             O
                                       D                   O                               D                       C       D
                                  C                                    R
                                          O                                                    O
                                     H                                                 H
                           H3C                                                                                    HO H          O
                            Harringtonolide                                                                                 4
                                   6                                               5
                                                                                                                           metathesis

                                   OH                                      O           CO2Et                               CO2Et
                                                                                H                                      H
                                           CHO
                                                                       O
                                                                           H           D                                    D
                               O       O
                                                  Diels-Alder                                         functional
                                                                                H                                  HO H
                                                                   O       O                            group
                             from D-glucose                                                        interconversion
                                   1                                           2                                       3



                                                                                                                                         2
So far, cycle D was successfully synthesised through a stereoselective intramolecular Diels-Alder reaction and
cycle C was obtained from the metathesis reaction of diene 3. After selective epoxidation and inversion of the
configuration of the allylic alcohol, attempts of cyclization are undertaken on compound 4. The final cyclization
step is also being investigated on a model compound.
Acknowledgments/Financial assistance:
The ANR is gratefully acknowledged for funding this project (ANR call « Jeunes Chercheurs et Jeunes
Chercheuses 2009 »)


1
    Buta, J.G., Flippen, J.L., Lusby, W.R. J. Org. Chem. 1978, 43, 1002-1003
2
    Abdelkafi, H., Evanno, L., Deville, A., Dubost, L., Chiaroni, L., Nay, B. Eur. J. Org. Chem. 2011 DOI : 10.1002/ejoc.201001678
Journées de Chimie Moléculaire 2011                                                                                                    Alexandre PRADAL
23 et 24 mai 2011



    Electrophilic activation of enynes : cycloisomerization reactions in the presence of
                                      gold-, platinum complexes or iodonium ions.
                                                       Dr. Véronique MICHELET et Dr. Patrick TOULLEC
                                                                   Dr. Anne Vessières-Jaouen
                               Laboratoire Charles Friedel, ENSCP Chimie ParisTech, 11 rue Pierre et Marie Curie, 75005, Paris
                                                        e-mail : alexandre.pradal@chimie-paristech.fr

Keywords: Enyne cycloisomerization, Gold and Platinum catalysis, iododonium ions.
                                                         1
         Enyne cycloisomerization reactions give easy access to complex molecular structures from simple precursors.
                                                                                                                 2                                3         4
These atom-economical reactions can be catalyzed by carbophilic Lewis acid complexes like gold and platinum
                                                                                                                                              5
catalysts or conducted in the presence of another type of electrophiles such as halonium ions. It has been recently
demonstrated in recent theoretical investigations that carbophilic Lewis acid catalysts and halonium ions could react
                           6
in the same manner.
         Our interest was focused on these two types of alkyne activation. On one hand, we investigated the
                                                                                                                                                            7
organometallic activation of 1,6-enynes for stereoselective cycloisomerization reactions in the presence of chiral gold
                 8
and platinum complexes. On the other hand, we studied the iodonium-mediated electrophilic carbocyclisation of 1,5-
                                                                                          9
enynes for the obtention of polysubstituted iodocyclopentenes.
         The latest results concerning these two types of enyne activation will be presented.
                                                                                                         R1 Nu                     H
                                                                                                     H                                  R2
                                          R1                                                                   R2                        R1
                                                                             [E+]   = [Pt, Au]   X                    or
                                                                        R1                                                     X
                                               R2                                                              R3                      R3

                                                                        R2                                            R1
                                              R3
                                                             [E]   R3                                    R'O
                                       [E+]                                    [E+] = I+                                  R3
                                                                                                     R
                                                                                                                     R3
                                                                                                          I


Acknowledgments/Financial assistance:
National Research Agency (ANR-09-JCJC-0078).

1
  Michelet, V.; Toullec, P. Y.; Genêt, J.-P. Angew. Chem. Int. Ed. 2008, 47, 4268. Pradal, A.; Toullec, P. Y.; Michelet V. Chemistry Today 2011, 29, in
press. Zhang, L.; Sun, J.; Kozmin, S. A. Adv. Synth. Catal. 2006, 348, 2271. Buisine, O.; Aubert, C.; Malacria, M. Chem. Rev. 2002, 102, 813. Jiménez-
Nùñez, E.; Echavarren A. M. Chem. Rev. 2008, 108, 3326.
2
  Belmont, P.; Parker, E. Eur. J. Org. Chem. 2009, 35, 6075. Toullec, P. Y.; Michelet, V. Top. Curr. Chem. 2011, in press.
3
  Reviews: Shapiro, N. D.; Toste, F. D. Synlett 2010, 675. Hashmi, A. S. K. Angew. Chem. Int. Ed. 2010, 49, 5232. Nevado, C. Chimia 2010, 64, 247.
4
  Chianese, A. R.; Lee, S. R.; Gagné, M. R. Angew. Chem. Int. Ed. 2007, 46, 4042. Fürstner, A.; Davies, P. W. Angew. Chem. Int. Ed. 2007, 46, 3410.
Fürstner, A. Chem. Soc. Rev. 2009, 38, 3208.
5
  Barluenga, J.; González, J. M.; Campos, J. M.; Asensio, G. Angew. Chem. Int. Ed. 1988, 27, 1546. Barluenga, J.; Palomas, D.; Rubio, E.; González, J. M.
Org. Lett. 2007, 9, 2823. Lim, C.; Rao, S.; Shin, S. Synlett 2010, 368. Crone, B.; Kirsch, S. F.; Umland, K.-D. Angew. Chem. Int. Ed. 2010, 49, 4661.
Harschneck, T.; Kirsch S. F.; Wegener, M. Synlett 2011, 1151.
6
  Yamamoto, Y.; Gridnev, I. D.; Patil, N. T.; Jin, T. Chem. Commun. 2009, 5075.
7
  Chao, C.-M.; Vitale, M. R.; Toullec, P. Y.; Genêt, J.-P.; Michelet, V. Chem. Eur. J., 2009, 15, 1319. Chao, C.-M.; Beltrami, D.; Toullec, P. Y.; Michelet,
V. Chem. Commun. 2009, 6988. Pradal, A.; Toullec, P. Y.; Michelet, V. Synthesis, 2011, 1501. Pradal, A.; Chao, C.-M.; Vitale, M. R.; Toullec, P. Y.;
Michelet, V. Tetrahedron, 2011, doi:10.1016/j.tet.2011.03.071
8
  Toullec, P. Y.; Chao, C.-M.; Chen, Q.; Gladiali, S.; Genêt, J.-P.; Michelet, V. Adv. Synth. Catal., 2008, 350, 2401. Toullec, P. Y.; Michelet, V. Curr. Org.
Chem., 2010, 14, 1245.
9
  Pradal, A.; Nasr, A.; Toullec, P. Y.; Michelet, V. Org. Lett. 2010, 12, 5222.
Journées de Chimie Moléculaire 2011                                                                 Moslem ALAAEDDINE

23 et 24 mai 2011




              New molecules of pyrannylidenes for photovoltaic conversion

                                                               Ludovic Tortech


                                                                Denis Fichou


                CEA-Saclay, Organic Nanostructures and Semiconductors Group, SPCSI/IRAMIS, 91191 Gif-sur-Yvette, France


                                     UPMC, IPCM, UMR CNRS 7201, 4 place Jussieu, 75005 Paris, France


                                                     E-mail : moslem.alaaeddine@cea.fr


Keywords: organic solar cells (OSCs), photovoltaic devices, interfacial layer (IFL), atomic force microscopy (AFM).




           OSCs have attracted attention due to their ease of fabrication and low-cost manufacturing. Nowadays
the research is focusing on the optimization of efficient photovoltaic systems through the using of new
materials and/or device structures.
           In our laboratory, we developed an original series of organic semi-conductors molecules 4, 4′-bis
(diaryl-2, 6-thiapyrannylidenes or pyrannylidenes) (DITPY-Ar4 and DIPY-Ar4).These molecules are planar quinoid
compounds, isoelectronic of tetrathiafulvalène and behave as strong π-donors. Because of their electronic and
structural properties, we developed solar cells having this material as active layer. Furthermore, their high hole
mobility allows to use them as efficient hole-transporting/electron-blocking layers in OSCs [1]. In order to
enhance the collection of charge at IFL, we used DIPY-Ar4 and DITPY-Ar4 with tetracyanoquinodimethane (n-
type) to synthesis a new paramagnetic compounds (conducting charge transfer).
           The Molecules were synthesized with different aromatic substituents, with respect of the molecular
design rules to increase the absorption, solubility and electronic properties.
           Electronic devices are elaborated by superposing thin organic layers (h<100nm).The layers are first
characterized by AFM and then inserted in a device structure (sandwich like); the component are finally studied
on an optical bench installed in a glove-box.




1-Dithiapyrannylidenes as Efficient Hole Collection Interfacial Layers in Organic Solar Cells, ACS Appl.
Mater. Interfaces, 2010, 2 (11), pp 3059–3068.
Journées de Chimie Moléculaire 2011                                                                 Ljubica SVILAR
23 et 24 mai 2011



 Study of nitrogenized azaphilones from fungi Hypoxylon Fragiforme by
           electrospray and H/D exchange mass spectrometry
                            Denis LESAGE, Sandra ALVES, Héloise SOLDI-LOSE, Vesna STANKOV-JOVANOVIC
                            Jean-Claude Tabet (Laboratoire de Chimie Structurale Organique et Biologique)
                               Bâtiment F72, 7ème Etage, Boite 45, 4 place Jussieu 75252 Paris Cedex 05
                                                  e-mail : ljubicasvilar@yahoo.com

Keywords: azaphilones, derivates, desolvation, H/D exchange.
        Azaphilones present a wide class of fungal metabolites with diverse biological activities, such as antimicrobial,
                                    (1)
antifungal, cytotoxic, nematicidal … Many of these reactivities can be explained by their potential to promote
nucleophilic attack to amino group, coming from amino acids, proteins and nucleic acids. It results in the formation of
the vinylogous -pyridones due to the exchange of pyran-oxygen by nitrogen during a complex pathway. Because of
their property to react with amino group, they were named azaphilones.
        In the earlier works, the azaphilones were mostly examined by HPLC/UV, by this way, they are isolated and
         (2)
analyzed . Reaction of azaphilones with amino group was detected by the LC/MS experiments of Hypoxylon
Fragiforme crude extract under unconventional electrospray conditions. For all detected azaphilones at different
retention times were noticed ions differing for one Th unit, while the abundance of new derivatives was not high as
already existing azaphilones in the fungal extract. Probably, due to these reasons, peaks of these derivatives in UV or
DAD chromatogram were not obvious, and these compounds were not detected. By ITMS, m/z values of protonated
derivated azaphilones were detected. FTMS gave accurate elemental compositions consisted with the presence of
nitrogen derivatives of existing azaphilones.
        Sampling has been done on the conventional way. Methanol extracts were purified by SPE, and as that, crude
extracts were analyzed by LC/ESI/MS, LC/ESI/FTMS and LC/ESI MSMS and LC/ESI/HDX/MS. MSMS experiments were
used for confirmation of both the azaphilone and their derivative structures. By applying different conditions in
electrospray ionisation, from soft to hard desolvation conditions, we have tried in this work to show the dependence
of naturally occurring nitrogen-containing azaphilone detection from the electrospray conditions. H/D exchange
experiment served to show the difference between the natural and nitrogenized azaphilones, and to confirm the
                                          (3)
existence of these azaphilone derivates .


    (1) N. Osmanova; W. Schultze; N. Ayoub. Phytochem Rev 2010, 9:315–342
    (2) M. Stadler; H. Wollweber Mycotaxon 2001, 77: 379-429
    (3) S. Campbell; M. T. Rodgers; E. M. Marzluff; J. L. Beauchamp, J. Am. Chem. Soc. 1994, 116: 9765.


Acknowledgments/Financial assistance: Thanks to French Government for supporting my thesis
Journées de Chimie Moléculaire 2011                                                 Benoît de CARNÉ‐CARNAVALET 
23 et 24 mai 2011 
 
 
                   Copper‐Free Sonogashira Coupling of Cyclopropyl Iodides  
                                                  with Terminal Alkynes 
                                                          Dr. Christophe MEYER 
                                                             Pr. Janine COSSY 
                     Laboratoire de Chimie Organique, ESPCI ParisTech, CNRS, 10 rue Vauquelin, 75231 Paris Cedex 05 
                                              e‐mail : benoit.de‐carne‐carnavalet@espci.fr 
 
Keywords: Sonogashira coupling, cyclopropyl iodide, alkynyl cyclopropane. 
 
        Substituted cyclopropanes are encountered in several synthetic and natural products displaying a broad 
spectrum of biological activities.1 To date, many efficient methods have been developed for the stereoselective 
preparation of cyclopropanes.2 Chemoselective palladium‐catalyzed cross‐coupling reactions, which allow the 
functionalization  of  the  three‐membered  ring  by  carbon‐carbon  bond  formation,  have  also  emerged  as  a 
particularly  useful  strategy.3  However,  despite  the  sp2  character  of  cyclopropanes,  only  a  few  examples  of 
cross‐coupling reactions involving cyclopropyl halides have been described.4,5 
        We have developed the first examples of Sonogashira coupling involving cyclopropyl iodides, allowing a 
straightforward access to a wide variety of functionalized alkynyl cyclopropanes in good yields.6 The reaction 
also tolerates many functional groups such as ethers, alcohols, amides or esters. 
         
         

                                                                PdCl2(MeCN)2 (3 mol %)
                                            R3     H               X-Phos (9 mol %)                             R3     H
                                           H           R2         Cs2CO3 (2.5 equiv)                           H           R2
                 R           H      +
                                           I           R1                                                                  R1
                                                             THF, 60 °C or toluene, 100 °C
                                                                                                        R
                                                                 4498% (31 examples)


                                                        R1 = CH2OH, CH2OPMB, CONHR4R5, CO2R6
                                                                        


        The optimization of the reaction conditions and the scope of this coupling will be presented. 
 
Acknowledgments/Financial  assistance:  Diverchim,  in  particular  Jean‐Louis  Brayer,  Benoît  Folléas  and 
Jean‐Pierre Demoute (Les Marches de l’Oise, 100 rue Louis Blanc, 60765 Montataire Cedex). 

1
  (a) Donaldson, W. A. Tetrahedron 2001, 57, 8589–8627.  (b) Reissig, H.‐U.; Zimmer, R. Chem. Rev. 2003, 103, 1151–1196. (c) Brackmann, 
   F.; de Meijere, A. Chem. Rev. 2007, 107, 4493–4537. 
2
  Lebel, H.; Marcoux, J.‐F.; Molinaro, C.; Charette, A. B. Chem. Rev. 2003, 103, 977–1050. (d) Pellissier, H. Tetrahedron 2008, 64, 7041–
   7095. 
3
  Gagnon, A.; Duplessis, M.; Fader, L. Org. Prep. Proc. Intl. 2010, 42, 1–69. 
4
  Charette, A. D.; De Freitas‐Gil, R. P. Tetrahedron Lett. 1997, 38, 2809–2812. 
5
  Cai, S.; Dimitroff, M.; McKennon, T.; Reider, M.; Robarge, L.; Ryckman, D.; Shang, X.; Therrien, J. Org. Proc. Res. Dev. 2004, 8, 353–359. 
6
  de Carné‐Carnavalet, B.; Archambeau, A.; Meyer, C.; Cossy, J.; Folléas, B.; Brayer, J.‐L.; Demoute, J.‐P. Org. Lett. 2011, 13, 956‐959.
:                                      D                                                                                D




                                                  E        D                                    W                  >
                                                                              '          
                                                                           W ,
                                            K      W s   '              W >    &                   W D    D
                      /              W                  D               hDZ      hWD              &              
                                                         W :                   W    


<


       E                                                                                                        /




d                              Z

                                                    [OTf]                                                                     [OTf]

                                    P                                                                               P Au Cl
                          Ru                        +                           CH2Cl2, rt
                                                             S Au Cl                                       Ru




                                                                                     WW         



                                                                                     [OTf]

                                                                       PPh2AuCl
                                                             Ru
                                                                             AgSbF6
                           HO                     OMe                                                                   OMe
                                                                             (2 mol%)
                                                                                                       O
                                        •                       CH2Cl2, rt, 15 min

                                                                       75%




       d


                      &                                     EZ         > E             ^  KZ



      D Z                 D                  D              D              : K                     &                 > '         s D   D
        > D              , K
    :     E                                D         Z
    '    : d     & E
    D      s d       Wz '                   : W             /     
Journées de Chimie Moléculaire 2011                                                                              Dénia MELLAL
23 et 24 mai 2011



                                  Synthesis of Analogues of Aminoacyl-tRNAs
                         for the study and the inhibition of FemX transferase
                                             Dr Mélanie Ethève-Quelquejeu & Pr Matthieu Sollogoub
                                                 UPMC – Institut Parisien de Chimie Moléculaire
                                          Equipe Glycochimie Organique Biologique et Supramoléculaire
                                             UMR CNRS 7201, 4 place Jussieu 75252 Paris Cedex 05
                                                              denia.mellal@upmc.fr

Keywords: FemX transferase, peptidoglycan, aminoacyl-tRNA.


             The tRNA-dependent aminoacyl Fem transferases catalyze an essential step of peptidoglycan synthesis
in bacteria and are considered as attractive target for the development of novel antibiotics. FemXwv, the
model enzyme of this family, transfers L-Ala from Ala-tRNA to the ε-amino group of L-Lys in the peptidoglycan
                                                                              (1), (2)
precursor UDP-MurNAc-pentapeptide, UM5K, (Scheme A).




Scheme A: Supposed Mecanism of bacterial FemX transferase                                 Scheme B: Analogue of Aminoacyl-tRNA bi-substrate


                                                                                                                     (3)
             Currently, we develop the semi-synthesis of highly modified aminoacyl-tRNAs                                   and bi-substrates
analogues to explore the catalytic mechanism of FemX. First, the synthesis of aminoacyl-tRNA analogues
containing an amide bond instead of the ester bond and the biological results will be presented. Secondly, our
preliminary results concerning the synthesis of bi-substrate analogues will be exposed (Scheme B).


Acknowledgments/Financial assistance:

(1)
      M. Fonvielle, M. Chemama, R.Villet, M. Lecerf, A. Bouhss, J-M. Valéry, M. Ethève-Quelquejeu, M. Arthur, Nucleic Acids Res., 2009, Vol.

                         (2)
37, No. 5, 1589-1601 ;         M. Fonvielle, M. Chemama, M. Lecerf, R. Villet, P. Busca, A. Bouhss, M. Etheve-Quelquejeu, M. Arthur Angew.

                                        (3)
Chem. Int .Ed. 2010, 49, 5115-5119 ;          M. Chemama, M. Fonvielle, M. Lecerf, D. Mellal, H. Fief, M. Arthur, M. Ethève-Quelquejeu, Current

Protocols in Nucleic Acid Chemistry, 2011, chapt. 4, Unit 4.44.
Journées de Chimie Moléculaire 2011                                                                       Bixue XU
23 et 24 mai 2011

         Synthesis of Monofluoro-Carbasugars and gem-Difluoro-Carbasugars
                       Supervisors: Prof. Matthieu SOLLOGOUB, Dr. Yongmin ZHANG, Dr. Melanie ETHEVE-QUELQUEJEU
                                                Directeur du Laboratoire: Prof. Max MALACRIA
                 Institut Parisien de Chimie Moléculaire, UMR 7201, Glycochimie Organique Biologique et Supramoléculaire
                                      Bâtiment F, 2ème étage, 4 place Jussieu, C. 181, 75005 Paris, France
                                                        e-mail : bixue_xu@hotmail.com

Keywords: Carbasugars; Fluorine; Mimics.
       Carbasugars are strictly defined as sugar analogues in which the endocyclic oxygen atom has been replaced
by a methylene group. Such replacement has the inherent disadvantage to suppress any possible hydrogen bond
formation that involved this electronegative atom.1 One way to circumvent this problem is replacement of the
endocyclic CH2 group by a CFH or CF2 moiety in a carbasugar. We have first synthesized gem-difluoro-
carbaglucose,2 gem-difluoro-carbamannopyranose and gem-difluoro-carbagalactopyranose.3 In this work, we
present the synthesis of methyl gem-difluoro-carba-α-D-glucopyranoside and methyl monofluoro-carba-α-D-
glucopyranoside with the retrosynthetic plan illustrated in Scheme 1. Our strategy is based on a Lewis acid,
triisobutylaluminum (TIBAL)4 or Cl3TiOiPr,5 induced rearrangement of an enolether possessing an electron-
donating group as illustrated in Scheme 2.6




Acknowledgments/Financial assistance:
    We thank the China Scholarship Council for a Ph.D. fellowship to Bixue XU.


1
  Montero, E.; Garcia-Herrero, A.; Asensio, J. L.; Hirai, K.; Ogawa, S.; Santoyo-Gonzalez, F.; Canada, F. J.; Jimenez-Barbero, J. Eur. J.
  Org. Chem. 2000, 1945-1952;
2
  Deleuze, A.; Menozzi, C.; Sollogoub, M.; Sinaÿ, P. Angew. Chem., Int. Ed. 2004, 43, 6680-6683;
3
  Sardinha, J; Guieu, S; Deleuze, A; Fernández-Alonso, M. C.; Rauter, A. P.; Sinaÿ, P.; Marrot, J.; Jiménez-Barbero, J.; Sollogoub, M. J.
  Carbohydr. Res., 2007, 342, 1689 - 1703;
4
  Das, S. K.; Mallet, J.-M.; Sinaÿ, P. Angew. Chem. 1997, 109, 51 3 - 516; Angew. Chem. Int. Ed. Engl. 1997, 36, 493 – 496;
5
  Sollogoub, M.; Mallet, J.-M.; Sinaÿ, P. Tetrahedron Lett. 1998, 39, 3471- 3472;
6
  Sollogoub, M.; Mallet, J.-M.; Sinaÿ, P. Angew. Chem. 2000, 112, 370-372; Angew. Chem. Int. Ed. 2000, 39, 362-364.
Journées de Chimie Moléculaire 2011                                                                                         Cécile HUBERT
23 et 24 Mai



     Detection of explosives on solid samples by high resolution mass spectrometry
                                                                   Jean-Claude TABETa
                                                             Xavier MACHURON-MANDARDb
     a
       Equipe de Spectrométrie de masse, Institut Parisien de Chimie Moléculaire, CNRS-UMR 7201, Université Pierre et Marie Curie-Paris VI, 4 place
                                           Jussieu, Bat F, 7ème étage, Boite 45, 75252 Paris Cedex 05, France
                                                        b
                                                          CEA, DAM, DIF, F- 91297 Arpajon, France
                                                                  cecile.hubert@cea.fr

Keywords: explosives; mass spectrometry; high resolution; ambient ionization sources.


          Explosives are widely used in military field and for civil purposes such as civil engineering, airbags or fireworks.
Their analysis is necessary for both the environmental monitoring of industrial sites and the forensic investigation of
explosions. Most of the time, explosives are present in samples at traces levels. Therefore, devices for their detection,
identification and quantitative analysis have to be sensitive, reliable and robust. Among the analytical instruments, the
mass spectrometer has become a method of choice.
          Mass spectrometry has evolved incredibly fast over the past 10 years. Very high resolution instruments giving
access to exact mass measurement are now commercially available. The Orbitrap spectrometer from Thermo Fisher is
                  1
one of them. Furthermore, recent and rapid advances in ionization sources have made it possible to ionize solid or
                                                                                                              2
liquid samples, directly under ambient conditions and without any sample preparation.




                                                         3D view of the Orbitrap mass analyzer



          Taking advantage of these improvements in the mass spectrometry field, an analytical protocol allowing
identification and quantification of several explosives from solid samples will be developed. The final aim of this work
is to draw a parallel between this direct ionization method coupled with high resolution mass spectrometry (HRMS)
and an extraction of the solid sample followed by a hyphenated liquid chromatography – mass spectrometry
technique. Preliminary results clearly demonstrate the huge potential of HRMS. Specific mass spectra of explosives
were obtained by the Orbitrap mass spectrometer, giving a better understanding of fragmentation mechanisms.
Moreover, wrong elemental composition assignments have been found in literature and corrected thanks to
unequivocal measurement of exact mass.




1
    Makarov, A. Anal. Chem. 2000, 72, 1156-1162.
2
    Venter, A.; Nefliu, M.; Cooks, R.G. Trends Anal. Chem. 2008, 27, 284-290.
Journées de Chimie Moléculaire 2011                                                          Viet Hung NGUYEN 
23 et 24 mai 2011 
              Concomitant EDD and EID of DNA evidenced by MSn and double 
                                resonance experiments 
                                            
                                                     Encadrant : Carlos AFONSO 
                                           Sous direction de professeur Jean Claude TABET 
                                                    ème 
                                             Bat F 7 étage, 4 place Jussieu 75005 Paris 
                                                                    
Keywords: EDD, FT/ICR, SORI‐CID 
 
Introduction  
            Under collisional activation conditions (CID), it is well known that dissociations of multideprotonated 
oligonucleotides  involve  an  initial  loss  of  nucleic  base  (formation  of  [M−nH‐Bi]n−)  yielding  consecutively  the 
                                                                                              B




complementary  (ai‐B)  and  wj  product  ions.  The  fragmentation  by  CID  depends  on  the  proton  affinity  of  the 
nucleobase,  so  that  the  loss  of  thymine  is  thermodynamically  unfavored  owing  to  its  low  proton  affinity. 
Recently,  EDD  (electron  detachment  dissociation)  activation  was  developed  by  Zubarev  et  al,  this  method 
produced fragment ions different from CID. In fact, under EDD 1  precursor ion lost one electron and it become 
radical ion; the electron remained (radical) is the factor which drives the fragmentation. 
 Results 
            The  SORI  CID  spectra  of  [M−2H]2−  ion  (m/z  884)  of  d(T2AT3)  display  direct  loss  of  AH.  However,  the 
complementary [a3‐A]−/w3− ions (m/z 705) emerge with similar abundances. Among the low‐abundant product 
ions, the complete wj− series is detected either as singly charged (w1−, w2− and w3−) or as doubly charged (w42− 
and  w52−)  ions.  It  should  be  noted  that  the  singly  charged  w4−  and  w5−  ions  were  not  detected.  EDD‐EID 
spectrum of [M−2H]2− ions (m/z 884) of d(T2AT3) displayed a complete series of singly charged wj− ions allowing 
a  simple  sequence  determination.  It  is  noteworthy  that  the  relative  abundance  ratio  between  w3−  (m/z  929) 
and  w52−  (m/z  760)  in  the  EDD–EID  spectrum  are  similar  to  that  displayed  in  the  SORI‐CID  spectrum. 
Furthermore,  the  w4−  (m/z  1218)  and  w5−  (m/z  1522)  singly  charged  ions  which  were  absent  in  the  SORI‐CID 
spectrum, appeared in the EDD–EID spectrum and the abundances of wj− ion series increased with the size of 
the product ions except for w3− which is enhanced due to the location of adenine. Interestingly some double 
charged  fragment  ions  were  also  detected.  MS3  and  double  resonance  experiment  were  investigated  to  find 
out  the  origin  of  these  fragment  ions,  it  turns  out  that  they  are  produced  through  direct  dissociation  from 
precursor ion without loss of electron, this process is called EID (electron induced dissociation). 
Conclusion 
EDD dissociation of DNA shows abundant loss of thymine. It is favored by a radical process whereas it is very 
difficult to achieve with conventional dissociation processes due to its lower proton affinity. The combination 
of  double  resonance  and  EDD/SORI‐CID  allows  decoupling  of  these  two  processes  which  distinguishes  the 
fragment ions that were produced from EID and those produced from “pure” EDD.   

1
    Viet Hung Nguyen, Carlos Afonso, Jean‐Claude Tabet; Int. Journal of Mass Spectro 301 (2011) 224–233 
Journées de Chimie Moléculaire 2011                                                                                         Carine ROBERT
23 et 24 mai 2011



                    Supported Neodymium Catalysts for Isoprene Polymerization:
                                 Modulation of Reactivity by Controlled Grafting
                                       Prof. Christophe Thomas1, Dr. Fréderic de Montigny1, Dr. Régis M. Gauvin2
                                                                 1
                                                                  ENSCP, UMR CNRS 7223,
                                                     11 rue Pierre et marie Curie 75231 Paris, France
                                                2
                                                 Université Lille Nord de France ENSCL, UMR CNRS 8181,
                                          Cité Scientifique, BP 90108, 59652 Villeneuve d’Ascq, Cedex, France
                                                        e-mail : carine-robert@chimie-paristech.fr

Keywords: catalysis; polymer ; controlled grafting
          A series of hybrid materials, bearing neodymium silylamide Nd[N(SiMe3)2]3 initiating groups, have been shown
to mediate isoprene polymerization when combined with alkyl aluminum activators [MAO, AlEt2Cl, Al(iBu)3]. The
surface species nature and relative distribution were correlated with isoprene polymerisation activity and selectivity.
Also, this approach to stereocontrol modulation has been extended to rac-β-butyrolactone (BBL) isoselective ring
opening polymerization. Therefore, simple silica grafting of molecular initiators affords materials bearing active sites
able to achieve high levels of stereocontrol in ROP of BBL. The most notable feature of grafted borohydride initiators,
and in particular of the neodymium complex, is to give significantly improved selectivities compared to homogeneous
catalysts. Indeed the neodymium-decorated silica converts the BBL monomer into highly isotactic poly(β-
                                                                                                                                  1
hydroxybutyrate). Under similar conditions, the molecular precursor gives rise to an atactic polymer.
                                                                                                                                  O

                                                                                                                              O
                                                                           R2N
                                                                                         NR2
                                                                                 Nd
                                                                      O     O
                                                                    SiSi
                                                                  O O O O Si O
                                                                  O
                                                                       O O
                                                                       SiO2                                            isospecif ic
                  regiospecif ic                                                                                         catalyst
                                             + MAO
                    catalyst



                                                                                                                        O
                                              n                                                                             O
                                                                                                                                n

                                                                                                              isotactic
                        cis-1,4-polyisoprene                                                          poly( -hydroxybutyrate)
Acknowledgments/Financial assistance:
This research was in part financially supported by the Région Ile-de-France, the ENSCP, the CNRS, and the French
Ministry of Research and Higher Education.


1
    Terrier, M.; Brulé, E.; Vitorino, M. J.; Ajellal, N.; Robert, C.; Gauvin, R. M. ; Thomas, C. M. Macromol. Rapid. Commun. 2011, 32, 215-219
Journées de Chimie Moléculaire 2011                                                                                  Benjamin MONTAIGNAC
23 et 24 mai 2011



          Combined Metal- and Amine-Catalyzed Intramolecular Addition of
               α-Disubstituted Aldehydes onto Unactivated Alkynes
                                       Directrices de these : Dr. Véronique Michelet, Dr. Virginie Vidal
                                                      Co-encadrant : Dr. Maxime Vitale
                 Laboratoire Charles Friedel UMR CNRS 7223 – Chimie ParisTech – 11, rue Pierre et Marie Curie 75005 Paris
                                                 benjamin-montaignac@chimie-paristech.fr

Keywords: metallo-organocatalysis / carbocyclization


           Over the past thirty years, transition-metal catalysis and then organocatalysis have grown
tremendously. Despite the broad range of reactions that has been rendered possible through the use of one of
these two types of catalysis, there still remain substrates that are unreactive or too sluggish in reactivity. In this
context, the concept of combining metal catalysis to organocatalysis has recently flourished and has led to the
                                                                                                                                    1
discovery of several new reactions that would not have been possible without the unusual association.
                                                                                 Cat 1
                                                                    A + B                      P
                                                                                 Cat 2


                                                          A*                                          B*


                                                 A                Metal                                          B
                                                                                 P*      Organocatalysis
                                                                 catalysis


                                                         Cat 1                                       Cat 2

                                                                                 P


           In this area, we discovered that the association of a catalytic quantity of a metal complex to the
catalytic use of either a secondary or primary amine allows the carbocyclization reaction of a wide range of α-
                                     2
disubstituted formyl alkynes. Highly functionalized carbo- and heterocycles bearing a quaternary stereogenic
                                                                             2
center were obtained in good to excellent yields. Different catalytic systems will be presented and the
influences of both the metal complex and the amine organocatalyst will be discussed.
                                             O                               Amine cat.                      O   R
                                                     R
                                         H                                   Metal cat .
                                                                                                           H
                                                     Z                                                               Z
                                    R = Me, Ph, n-Bu, Bn
                                 Z = C(CO2Me)2, C(SO2Ph)2
                                      C(CH 2OR')2 , NTs



Acknowledgments/Financial assistance: MESR/UPMC fellowship


1
  (a) Shao, Z.; Zhang, H. Chem. Soc. Rev. 2009, 38, 2745 (b) Zhou, J. Chem. Asian J. 2010, 5, 422 (c) Zhong, C. Shi, X. Eur. J. Org. Chem. 2010,
2099.
2
  (a) Montaignac, B.; Vitale, M. R.; Michelet, V.; Ratovelomanana-Vidal, V. Org. Lett. 2010, 12, 2582 (b) Montaignac, B.; Vitale, M. R.;
Ratovelomanana-Vidal, V.; Michelet, V. J. Org. Chem 2010, 75, 8322 (c) Montaignac, B.; Vitale, M. R.; Ratovelomanana-Vidal, V.; Michelet,
V. Eur. J. Org. Chem. 2011, accepted.
Journées de Chimie Moléculaire 2011                                                       Thomas COCHET
23 et 24 mai 2011



(E)-Dimethyl 2-oxopent-3-enylphosphonate: An Excellent Substrate
    for Cross-Metathesis. An access to Functionalized Heterocycles


                                                  Veronique BELLOSTA
                                                        Janine COSSY
             Laboratoire de Chimie Organique, ESPCI ParisTech, CNRS, 10 rue Vauquelin, 75231 Paris Cedex 05
                                              e-mail : thomas.cochet@espci.fr




Keywords: Metathesis, heterocycles, tandem reaction.


Nowadays, metathesis is a powerful and atom economical reaction for the construction of di- and
                            1,2,3
tri-substituted olefins.            In addition, cascade reactions or one-pot processes can take place induced
                                                                                                                     4
by the catalyst itself, by modification of the catalyst in situ, or by different chemoselective catalysts.
One part of our work is dealing with the use of the γ,δ-unsaturated β-ketophosphonate 1 as the key
starting material for obtaining unsymmetrical divinyl ketones of type A or functionalized heterocycles of
type B. A and B are useful intermediates for the synthesis of natural products. A cross-metathesis
reaction was developed between 1 and different olefins for obtaining enones C and, depending on the
reaction conditions and the partners, an in situ 1,4-addition can occur to afford directly cyclized
compounds of type B in cascade reaction.


                                                                                                                         R''
           O O                          CM                                   CM / 1,4 addition
    MeO                                              MeO        O O                                  MeO       O O   X
       P                                                    P                                              P
    MeO                 R                                                                       XH
              C                                       MeO                                            MeO                 n
                                          R                      1                   n
                                                                                                                 B
                                                                                          R''
      R'CHO       HWE

              O                                                              X = O or X = NP
                                                                             n = 1 or 2
    R'                  R
             A
Unsymetrical divinyl ketones




Financial assistance: Edelris



1
  Nolan, S. P.; Clavier, H. Chem. Soc. Rev. 2010, 39, 3305-3316.
2
  Samojłowicz, C.; Bieniek, M.; Grela, K. Chem. Rev. 2009, 109, 3708-3742.
3
  Hoveyda, A. H.; Zhugralin, A. R. Nature 2007, 450, 243-251.
4
  Alcaide, B.; Almendros, P.; Luna, A. Chem. Rev. 2009, 109, 3817-3858.
Journées de Chimie Moléculaire 2011                                                                          Benjamin MATT
23 et 24 mai 2011



                      Hybrid polyoxometalates for solar energy conversion
                                                        Guillaume Izzet, Anna Proust
                                                       Equipe Polyoxométallates,
                                       Institut Parisien de Chimie Moléculaire UMR CNRS 7201,
                                 UPMC Université Paris 06, 4, place Jussieu, 75252 Paris Cedex 05, France.
                                         Benjamin.matt@upmc.fr, Guillaume.izzet@upmc.fr


Keywords: Polyoxometalates based hybrids, Chromophores, Electron transfer, Artificial photosynthesis


          Polyoxometalates (POMs), form a remarkable class of well-defined nanoclusters with an unmatched
                                               1
diversity of structures and properties. They currently receive considerable interest because of their wide range
                                                                                                                             2
of applications in many fields such as analytical chemistry, catalysis, materials science, and medicine. An
important property of most POMs is their ability to reversibly accept and release specific numbers of electrons
under minor structural rearrangement. Therefore, POMs are attractive candidates for the development of
photochemical devices aiming at photocumulative electron transfer. The Polyoxometalates group in Paris has a
                                                           3
long tradition in the functionalization of POMs. In this context, we are interested to prepare inorganic/organic
POM-based hybrid in which the POM would be covalently connected to a photoactive antenna for performing
solar energy conversion.




     We herein describe a new strategy of covalent attachment of organic and/or organometallic fragments to
                                                                              4,5
an organo-silyl POM-based hybrids via Sonogashira couplings.                        The electronic and photophysical properties of
these hybrids will be presented.


Acknowledgments/Financial assistance: MESR

                                                                     1



1
  Special issue devoted to polyoxometalates, ed. C. L. Hill, Chem. Rev., 1998, 98, 1–390.
2
  D.-L. Long, R. Tsunashima, and L. Cronin, Angew. Chem. Int. Ed. 2010, 49, 1736-1758.
3
  A. Proust, R. Thouvenot, and P. Gouzerh, Chem. Commun., 2008, 1837-1852.
4
  V. Duffort, R. Thouvenot, C. Afonso, G. Izzet, and A. Proust, Chem. Commun., 2009, 6062–6064.
5
  B. Matt, S. Renaudineau, L-M. Chamoreau, G ; C. Afonso, G. Izzet, A. Proust, J. Org. Chem., 2011, 3107-3112.
Journées de Chimie Moléculaire 2011                                                                   Carole SAUER
23 et 24 mai 2011


                 Green and non-toxic functionalization of metal oxide surfaces:
                                                         Application to ITO
                              Sauer Carolea,b, Michelet Véroniquea, Toullec Patricka, Hoang Antoineb, Marchand Gillesb
                                                                  Vinet Françoiseb
                a
                  Laboratoire Charles Friedel, ENSCP Chimie ParisTech, UMR7223, 11 rue Pierre et Marie Curie, 75231 Paris Cedex 05
          b
            Laboratoire Fonctionnalisation et Chimie pour les Microsystèmes, CEA Grenoble, 17 rue des Martyrs, 38054 Grenoble Cedex 9
                                                            e-mail : carole.sauer@cea.fr

Keywords: Microwave, Click Chemistry, Green, Functionalization


           Implantable microsystems monitoring the brain activity or some brain pathologies have recently attracted
                    1
growing interest. Indeed, microsystems have very small dimensions for insertion into the brain and can integrate
several different sensors on the same device. However, these medical implants have to be sterile, biocompatible and
non-toxic in vivo to avoid rejections and complications such as infection or inflammation.
Indium Tin Oxide (ITO) is a material of choice to be used in these medical devices due to its biocompatible and
conductive properties. Furthermore, ITO surface properties can be tailored by grafting organic molecules such as
phosphonates. To address the requirements concerning the in vivo non toxicity, both the phosphonates syntheses and
the functionalization of the ITO surface must be performed according to green and non-toxic processes. The well-
                                                                        2
known concept of Click Chemistry introduced by Sharpless is expected to fulfil mainly these requirements.
We have been interested in developing new green synthesis of functionalized phosphonates and novel ITO
functionalization to introduce various functional groups onto the surface.
                                                                                                                     3
           The photochemically-assisted reaction between an alkene and a range of thiols has been successfully
performed to make a click reaction thiol-ene starting from a commercially available alkenyl-based phosphonate. This
synthetic process allows the obtention of a class of functionalized phosphonates leading upon grafting on the surface
to an array of biotechnological applications.
                                                                            4
           Considering the recent work from Yousaf et al., we also envisaged to prepare carbonyl-functionalized
surface in a one-step reaction, which would be suitable to react with biological molecules like peptides. A microwave-
assisted green synthesis of keto-functionalized phosphonates has been developed: the reaction occurs through a
catalyzed synthesis in aqueous medium.
           In parallel, a protocol has been developed to graft phosphonic acids and phosphonates on ITO surfaces
under green conditions.
   The novel synthesis of functionalized phosphonates and their grafting on ITO surfaces will be discussed.


Acknowledgments/Financial assistance: CEA (Commissariat à l’Energie Atomique et aux Energies Alternatives)

   1
     Receveur, R. A. M.; Lindemans, F. W. and Rooij, N. F. d. J. Micromech. Microeng., 2007, 17, R50-R80.
   2
     Kolb, H. C.; Finn, M. G. and Sharpless, K. B. Angew. Chem. Int. Ed., 2001, 40, 2005-2021.
   3
     Weinrich, D.; Köhn, M.; Jonkheijm, P.; Westerlind, U.; Dehmelt, L.; Engelkamp, H.; Christianen, P. C. M.; Kuhlmann, J.; Maan, J. C.; Nüsse,
   D.; Schröder, H.; Wacker, R.; Voges, E.; Breinbauer, R.; Kunz, H.; Niemeyer, C. M. and Waldmann, H. ChemBioChem, 2010, 11, 235 – 247.
   4
     Pulsipher, A.; Westcott, N. P.; Luo, W. and Yousaf, M. N. Adv. Mater., 2009, 21, 3082-3086.
Journées de Chimie Moléculaire 2011                                                       Meihui ZHENG 
23 et 24 mai 2011 
 
 

                  Design and development of a cathode modified by laccases
                                                           Dr Claude Jolivalt 
                                                           Dr Anne Vessières 
                                         11, rue Pierre et Marie Curie, 75231 PARIS Cedex 05 
                                              E‐mail : meihui‐zheng@chimie‐paristech.fr 
 
Keywords: biofuel cell, laccase, direct electron transfer (DET) 
 
    In the perspective of the development of sustainable energy, a biofuel cell is presented as an alternative to the 
fossil energy. The biocatalyst whose biological function in vivo is the catalysis of the redox reaction, is used to resolve 
the problem of the limitation of the developed power.  
    Our team aims at developing a cathode for biofuel cell using the laccase which catalyses the reduction of the O 2  to 
H 2 O. A laccase of the T. versicolor produced in the laborary is selected because of its good stability and its high redox 
potential. The laccase is covalently bound to the electrode functionalized by plasma or by electrochemical methods. 
Its operational stability and the direct electron transfer (DET) in absence of redox mediators are then assayed. The 
enzymatic activity on the electrode is measured with ABTS as substrate, while the efficiency of the electrode modified 
by laccase is tested by electrochemical methods. 
    The effects of the different parameters on the DET are investigated for the optimization of the immobilization of 
the laccase. Subsequently, the quantity of the laccases immobilized should be increased for enhancing the power of 
the biopile. Furthermore, the orientation of the laccases should be controlled by the engineering of the enzyme for 
optimizing the DET. 
 




                                                                                                      
 
 
Acknowledgments/Financial assistance: Dr. Claude Jolivalt, Pr. Farzaneh Arefi‐Khonsari, Dr. Jérôme PULPYTEL , Dr. 
Malika ardhaoui, Dr. Sophie Griveau, Sudhir BHATT 
Journées de Chimie Moléculaire 2011                                                                 Gilles Alex Pakora

23 et 24 mai 2011

    PURIFICATION AND CHARACTERIZATION OF SECONDARY METABOLITES OF
           COCOA ENDOPHYTIC FUNGI. STUDY OF THEIR ACTIVITY AND THEIR
                                                    BIOTRANSFORMATION
                                                    1                                           2
                    Codirection: Didier BUISSON , Chargé de Recherches CNRS, Daouda KONE , Maître de Conférences
                               1
                                   UMR 7245, Molécules de Communication et Adaptation des Micro-organismes (MCAM),
                                           2
                                               Laboratoire de Physiologie Végétale Université de Cocody-Abidjan
                                                           Directrice UMR 7245 : Sylvie Rebuffat,
                                                                 63 rue Buffon 75005 Paris
                                                                 pakoragillesalex@yahoo.fr

Keywords: Trichoderma sp, Phytophthora, antagonism, biocontrol agents

          Cocoa black pod disease in Côte d ivoire, due to Phytophthora palmivora and Phytophthora
megakarya, can cause crop losses up to 30%. There are several control methods including biological control,
more environmentally friendly and better for the consumer food safety. To initiate this method, studies
conducted by the Centre National de Recherche Agronomique de Côte d'Ivoire has isolated 43 strains of
Trichoderma sp, four isolates were found to be very effective against P. palmivora in vitro and in vivo1.
However these four isolates did not effective against P. megakarya, assuming the ability of P. megakarya
inactivate Trichoderma secondary metabolites by biotransformation. Our study aims to determine the
molecular structure of Trichoderma secondary metabolites inhibiting the growth of P. palmivora and to study
their biotransformation by P. megakarya. We have isolated two sesquiterpene and a diketopiperazine.
                                                                                                                         2
We have isolated two diketopiperazines (1- Cyclo-(Tyrosine-Proline) 2- Cyclo-(Valine-Proline))                               and
sesquiterpene.




          1                                                              2

These 2 diketopiperazines have no antagonist activity against P. palmivora but may be precursors of active
molecules whose biosynthesis is being studied.

Acknowledgments/Financial assistance: Côte d Ivoire State




1-J Mpika, IB Kebe, Sciences &Nature, 2009, 6, 49-62.
2-Gamini S Jayatilake, Maureen P. Thornton, J. Nat. Prod, 1996, 59, 293-296.
Journées
de
Chimie
Moléculaire
2011
                                      
        
         
          Aude
COLON

23
et
24
mai
2011





                                     DNA‐Based
Asymmetric
Catalysis

                                                     Dr.
Stellios
ARSENIYADIS

                                                          Pr.
Janine
COSSY

                    Laboratoire
de
Chimie
Organique
de
l'ESPCI
ParisTech,
10,
rue
Vauquelin,
75231
PARIS
CEDEX
5

                                                    e‐mail
:
audecolon@free.fr



Keywords:
DNA,
biohybrid,
asymmetric
catalysis,
rhodium
catalysis.




        Due
to
its
characteristic
right‐handed
helix
structure
and
to
its
versatile
achitecture,
DNA
has
become

an
interesting
source
of
chirality
for
the
development
of
enantioselective
reactions.
During
the
last
five
years,

considerable
efforts
have
been
devoted
to
the
development
of
DNA‐based
asymmetric
catalysis
resulting
in
the

discovery
 of
 a
 few
 effective
 catalytic
 processes,
 such
 as
 Diels‐Alder,
 Friedel‐Craft
 reaction,
 Michael
 addition,

                                                     [1]
fluorination
 or
 kinetic
 resolution
 processes. 
 These
 catalysts
 incorporate
 a
 small
 molecule
 anchored
 in
 a

covalent
or
non‐covalent
fashion
to
DNA.


        For
our
part,
we
have
focused
our
studies
on
the
synthesis
of
new
non‐chiral
ligands
bearing
a
diene

motif
 linked
 to
 a
 DNA‐intercalating
 agent
 and
 their
 use
 in
 asymmetric
 catalysis,
 particularly
 in
 the
 field
 of

rhodium‐catalyzed
conjugate
addition
of
boronic
acids
on
enones.





                                                                   DNA intercalant                      Spacer

                                                                                                                    n

                                                               n                   n




                           [M]                             N

                                                  acridine type           anthracene type             pyrene type
           [M]-DNA hybrid                                                                                               

                                                                     



Acknowledgments/Financial
assistance:
MRT,
ANR





                                                                     

                                                                     





[1]
For
a
review,
see
:
A.
J.
Boersma,
R.
P.
Megens,
B.
L.
Feringa,

G.
Roelfes,
Chem.
Soc.
Rev.,
2010,
39,
2083‐
2092.

Journées de Chimie Moléculaire 2011                                                                     Florence MAUGER
23 et 24 mai 2011



                                  Development of a DNA sequencing method
                                       using cleavage of RNA/DNA chimeras
                                         and MALDI-TOF mass spectrometry
                                                    Pr. Jean-Claude Tabet et Dr. Ivo Gut
                                                             Dr. Mark Lathrop
                                       CEA/DSV/IG/CNG/LDTP 2 rue Gaston Crémieux 91057 EVRY CEDEX
                                                     e-mail : florence.mauger@cng.fr

Keywords: DNA sequencing, RNA/DNA chimeras and MALDI-TOF MS


                                                                                                1 2
             As the DNA sequence of the human genome is now completed                                 and available, interest is shifting to
the detection of human diseases at genetic level. Thus, rare, private and unknown polymorphisms on
candidate genes can be identified through developement of new methods of sequencing for each individual.
             We have developed a new method for DNA sequencing using RNA/DNA chimeras and MALDI-TOF
                                                                                                                                     3
mass spectrometry. The method takes advantage of a novel class of thermostable DNA polymerases that also
incorporate ribonucleotides. The RNA/DNA chimeras contain three deoxyribonucleotides and the fourth
                                                                                                                                            4 5
nucleotide in its ribonucleotide form. These products can be either a single-stranded linear extension                                        or a
double-stranded ribo-PCR. The RNA/DNA chimeras are cleaved by sodium hydroxyde after each ribonucleotide
base. All fragments contain only one ribonucleotide 3’ terminal base with a phosphate terminal group.
Fragments are desalted by the addition of cation exchange resin and masses are determined by MALDI-TOF
mass spectrometry. The mass fingerprint is used to identify deviations from the reference sequence. With the
high throughput capability of mass spectrometry, this facile method is well suited for screening DNA sequences
of limited regions of interest in a large number of individuals.
                                                                           4                                                         5
             Potential applications include: DNA genotyping , DNA micro-haplotyping, DNA sequencing and DNA
methylation analysis. In addition somatic mutations can be analyzed with this novel, rapid and accurate
concept.


Acknowledgments/Financial assistance: This work was supported by the French Ministry of Education
Research and the European Community’s Seventh Framework Program-READNA.

1
    Venter, J.C et al. Science. 2001, 291, 1304-1351
2
    Lander, E.S et al. Nature. 2001,409, 860-921
3
    Schönbrunner, N.; Fiss,, E.; Budker, O.; Stoffel, S.; Sigua, C.; Gelfand, D. and Myers, T. et al. Biochemistry. 2006, 45, 12786-12795
4
    Mauger, F.; Jaunay, O.; Chamblain, V.; Reichert, F.; Bauer, K.; Gut, I. and Gelfand, D. Nucleic Acids Research. 2006, 34,e18
5
    Mauger F.; Bauer, k.; Calloway, C.; Semhoun, J.; Nishimoto, T.; Myers, T.; Gelfand, D. and Gut, I. Nucleic Acids Research. 2007, 35,e62
Journées de Chimie Moléculaire 2011                                                                                 Ludovic Halby
23 et 24 mai 2011



      Synthesis of new DNMT inhibitors: Rapid synthesis and in-vitro activity of
                                                    procainamide derivatives
                                                        Paola Arimondo & Clotilde Ferroud
                                     USR3388 ETaC CNRS-PierreFabre 3 avenue Curien 31100 Toulouse, France
                                     ERL 3193 – CNRS, ESPCI ParisTech, CNAM, 2 rue Conté 75003 Paris France
                                         e-mail : paola.arimondo@dr14.cnrs.fr, clotilde.ferroud@cnam.fr

Keywords: procainamide derivative, DNA methyltansferase, DNMT inhibitor, epigenetic.


               Epigenetic modifications are known to control gene expression. In mammals, methylation of

deoxycytidines was shown to be a major factor of the epigenetic regulation and occurs at CpG sites, which are
                                                                                             1-3
enriched in so-called CpG islands often located in genes promoters                                . The addition of a methyl group on the
                                                                                                                        4-6
carbon-5 position of the cytosine is catalysed by the C5 DNA methyltransferases (DNMT)                                     . The impairment of

epigenetic information can compromise the normal development of an organism and is involved in various
                                    7, 8
diseases, such as cancer                . Cancerous cells often present two types of aberrant DNA methylation: a global

hypomethylation leading to genomic instability, and a specific hypermethylation of the promoters of certain

genes, such as tumor suppressor genes, which silences them. Interestingly, epigenetic modifications are

reversible and it has been shown that inhibitors of DNMTs are able to demethylate the promoters and
                                                 9-11
reactivate tumor suppressor genes                    . Therefore DNMT inhibitors are a great promise for the development of

new and more efficient anticancer strategies. Here we synthesized several conjugates of procainamide by

developing a new and rapid synthetic pathway. We found six potent inhibitors of the murine catalytic

DNMT3A/3L complex and of human DNMT1, at least 50-folds more active than the parent compounds. The

inhibitors showed selectivity for C5 DNA methyltransferases. The cytotoxicity of the inhibitors was validated on

two tumoral cell lines. The inhibition potency of procainamide conjugated to phtalimide through alkyl linkers

depended on the length of the linker, the dodecane linker being the best.

1                                                                2
    Illingworth, R. S.; Bird, A. P. FEBS Lett 2009, 583, 1713-20. Berger, S. L.; Kouzarides, T.; Shiekhattar, R.; Shilatifard, A. Genes Dev 2009, 23,
          3                                                                                                                              4
781-3. Weber, M.; Hellmann, I.; Stadler, M. B.; Ramos, L.; Paabo, S.; Rebhan, M.; Schubeler, D. Nat Genet 2007, 39, 457-66. Cheng, X.;
                                                        5                                                                     6
Blumenthal, R. M. Structure 2008, 16, 341-50. Goll, M. G.; Bestor, T. H. Annu Rev Biochem 2005, 74,481-514. Jeltsch, A. Curr Top
                                            7                                                      8
Microbiol Immunol 2006, 301, 203-25. Esteller, M. N Engl J Med 2008, 358, 1148-59. Sharma, S.; Kelly, T. K.; Jones, P. A. Epigenetics
                                    9                                                        10
Carcinogenesis 2010, 31, 27-36. Yu, N.; Wang, M. Curr Med Chem 2008, 15, 1350-75.              Mai, A.; Altucci, L. int J Biochem Cell Biol 2009, 41,
              11
199-213.       Szyf, M. Annu Rev Pharmacol Toxicol 2009, 49, 243-63.
Journées de Chimie Moléculaire 2011                                                                                  Huanhuan QU
23 et 24 mai 2011



                Synthesis and anticancer activities study of Glycosphingolipids
                                                            Supervisor: Yongmin Zhang
                                                    Directeur du Laboratoire: Max MALACRIA
                          Université Pierre et Marie Curie - Paris 6, Institut Parisien de Chimie Moléculaire (UMR 7201),
                                       batiment F74, 2er étage, C. 181, 4 place Jussieu,75005 Paris, France
                                                             e-mail : aiby116@163.com

Keywords: glycosphingolipids; synthesis; anticancer


            Glycosphingolipids (GSLs) are cell-surface antigens, it was suggested that changes in their composition
would result in changes in the ability to bind antibody and ability to induce immune response of the tumor cells
expressing them1. The idea of GSLs as tumor-associated antigens is the basis for attempts to utilize them for
anticancer vaccine development2. Recently, our research group focused on GM3 (Fig. 1) which was expressed
in melanoma and many other human and animal cancers3.




                                                  Fig. 1 GM3 glycosphingolipid antigen
            Based on the structure modification of GM3, we have successfully synthesized several analogues (Fig.
2) of this type of glycosphingolipid antigen.




                                                 Fig. 2 Target glycosphingolipid antigen
            Going a step further, these target glycosphingolipids obtained will be used for screening anticancer
agents.


Acknowledgments/Financial assistance: China Scholarship Council (CSC)

1
    Hakomori, S. J. Biol. Chem. 1990, 265,18713-18716.
2
    Tillack, T. W.; Allietta, M.; Moran, R. E.; Young, W. W. J. Biochim. Biophys. Acta. 1983, 733, 15-24.
3
    Zhang, Y. Iwabuchi, K. Nunomura, S. Hakomori, S. Biochemistry. 2000, 39, 2459-2468.
Journées de Chimie Moléculaire 2011                                                                    Baiyi XUE

23 et 24 mai 2011



Structural Characterization of Antibody Drug Conjugates in Animal Plasma by High

                                     Resolution Mass Spectrometry
                                    Sandra ALVES, Olivier PASQUIER and Patrick SOUBAYROL
                                                     Jean-Claude TABET
                                             4 place JUSSIEU, BAT F, 7ème étage
                                                  e-mail : b.xue@hotmail.fr



Keywords: antibody-drug-conjugates, affinity capture LC-MS



     The antibody drug conjugates (ADCs) concept is an emerging technology of targeted therapy for cancer.

Humanized monoclonal antibodies, linking with anticancer drugs (cytotoxics), are used as vehicle to achieve the

targeted anticancer drug delivery. Healthy cells are not or little damaged and meanwhile, cancer cells are killed with

more efficacy. However, premature release of the cytotoxic drugs during circulation can lead to undesired

non-targeted toxicity and reduce efficacy. Therefore, it is important to have a good understanding of the stability of

ADCs in plasma. In order to characterize ADCs, sensitive affinity capture LC-MS method has to be developed to

measure the various drug-to-antibody ratios (DARs) of the intact antibody. The challenge is due to complexity of the

background plasma and the difficulty on isolating ADCs from the other proteome present in the plasma. The highly

sensitive mass spectrometry, equipped with powerful mass reconstruction software, allows a ready characterization

of ADCs in plasma.
Journées de Chimie Moléculaire 2011                                               Florent Le Boucher d’Hérouville
23 et 24 mai 2011



                 Strategies for the synthesis of atropoisomeric diphosphines
                                                                   Dr. V. Michelet
                                  Laboratoire Charles Friedel, 11 rue Pierre et Marie Curie, 75231 Paris , Cedex 05
                                                e-mail :florent-le-boucher@etu.chimie-paristech.fr

Keywords: atropoisomeric diphosphine, phosphorylation, Grignard reagent, transition metal coupling.
                                                                                                                                  1
           Since the discovery of the atropoisomeric binaphtyl Binap                                                                  ligand, new
atropoisomeric ligands appeared in the literature and have been the essential chiral inducers
of important breakthrough on asymmetric catalysis.2 One common aspect of the synthesis of
atropoisomeric diphosphines and key step is a phosphorylation reaction, which is based on
two main general strategies: the first one implies a Grignard addition to phosphane
intermediates,3 whereas the second one involves a Pd- or Ni- coupling reaction.4
                                  X
                                                   Y
                              *         +
                                                Cl PR2
                                  X
                                                                           Y
                                                         Mg or Li          PR2     [Pd] or [Ni]       OTf
                                           or                                                                               Y
                                                                       *                          *             +
                                                                                                                          X PR2
                                  Y                                        PR2                        OTf
                                  P(GP)2                                   Y
                              *                 +   RX
                                  P(GP)2
                                  Y                                                                         X = H or Cl
                                                                            Y=O                             Y = O or
                                                                            reduction

                                  X = Hal
                                  Y = O or
                                  GP = Leaving Group                       PR2
                                                                       *
                                                                           PR2



The general strategies and seminal examples will be presented.
Acknowledgments/Financial assistance: CNRS/Hoffmann-La Roc

1
  (a) Noyori, R. in Asymmetric Catalysis in Organic Synthesis, Wiley: New York, 1994. (b) Ojima, I.; Ed. in Catalytic Asymmetric Synthesis;
Wiley-VCH: New York, 2000.
2
  (a) Shimizu, H. ; Nagasaki, I.; Saito, T. Tetrahedron 2005, 61, 5405. (b) Berthod, M.; Mignani, G.; Woodward, G.; Lemaire, M. Chem, Rev.
2005, 105, 1801. (c) Tang, W.; Zhang, X. Chem, Rev. 2003, 103, 3029.
3
  (a) Takaya, H.; Mashima, K.; Koyano, K.; Yagi, M.; Kumobayashi, H.; Taketomi, T.; Akutagawa, S.; Noyori, R. J. Org. Chem. 1986, 51, 629. (b)
Mashima, K.; Kusano, K.; Sato, N.; Matsumura, Y.; Nozaki, K.; Kumobayashi, H.; Sayo, N.; Hori, Y.; Ishizaki, T.; Akutagawa, S.; Takaya, H. J.
Org. Chem. 1994, 59, 3064. (c) Casalnuovo, A.L.; Rajanbabu, T.V.; Ayers, T.A.; Warren, T.H. J. Am. Chem. Soc. 1994, 116, 9869. (d) Pai, C.-C.;
Lin, C.-W.; Lin, C.-C.; Chen, C.-C.; Chan, A. S. C.; Wong, W. T. J. Am. Chem. Soc. 2000, 122, 11513. (e) Qiu, L.; Kwong, F. Y.; Wu, J.; Lam, W. H.;
Chan, S.; Yu, W.-Y.; Li, Y.-M.; Guo, R.; Zhou, Z.; Chan, A. S. C. J. Am. Chem. Soc. 2006, 128, 5955. (f) Zhang, H.-W.; Meng, Q.-H.; Zhang, Z.-G.
Chin. J. Chem. 2008, 26, 2098. (g) Schmid, R.; Broger, E. A.; Cereghetti, M.; Crameri, Y.; Foricher, J.; Lalonde, M.; Muller, R. K.; Scalone, M.;
Schoettel, G.; Zutter, U. Pure Appl. Chem. 1996, 68, 131. (h) Duprat de Paule, S. ; Jeulin, S. ; Ratovelomanana-Vidal, V.; Genet, J.-P.;
Champion, N.; Dellis, P. P. Org. Process. Res. Dev. 2003, 7, 399. (i) Jeulin, S. ; Duprat de Paule, S. ; Ratovelomanana-Vidal, V.; Genet, J.-P.;
Champion, N.; Dellis, P. Angew. Chem. Int. Ed. 2004, 43, 320. (j) Berhal, F. ; Esseiva, O. ; Martin, C.-H. ; Tone, H. ; Genet, J.-P. ; Ayad, T. ;
Ratovelomanana-Vidal, V. Org. Lett. 2011, DOI: 10.1021/ol200495a.
4
  (a) Cai, D.; Payack, J.; Bender, D. R.; Hughes, D. L.; Verhoeven, T. R.; Reider, P. J. J. Org. Chem. 1994, 59, 7180. (b) Ager, D. J.; East, M. B.;
Eisenstadt, A.; Laneman, S. A. Chem. Commun. 1997, 2359. (c) Knöpfel, T. F.; Aschwanden, P.; Ichikawa, T.; Watanabe, T.; Carreira, E. M.
Angew. Chem. Int. Ed. 2004, 43, 5971. (d) Uozumi, Y.; Tanahashi, A.; Lee, S.; Hayashi, T. J. Org. Chem. 1993, 58, 1945. (e) Drießen-Holscher,
B.; Kralik, J.; Agel, F.; Steffens, C.; Hu, C. Adv. Synth. Catal. 2004, 346, 979.
Journées de Chimie Moléculaire 2011                                                         Bruno ANXIONNAT 
23 et 24 mai 2011 
 
 
                   Monoalkylation of acetonitrile using primary alcohols 
                                                   Dr. Domingo GOMEZ PARDO 
                                                         Pr. Janine COSSY 
                   Laboratoire de Chimie Organique de l’ESPCI ParisTech, 10, rue Vauquelin, 75231 PARIS CEDEX 5 
                                                 e‐mail : banxionnat@gmail.com 
 
Keywords: iridium catalysis, hydrogen transfer, ‐alkylation 
          
         Nitriles are useful compounds as they can be easily transformed to a diversity of functions like amides, 
amines, carboxylic acids, aldehydes, ketones, … In this context, the monoalkylation of acetonitrile, a very cheap 
starting material, represents a challenge to access complex nitriles, as the alkylation of acetonitrile is generally 
performed using a sub‐stoechiometric amount of strong base or a cyanomethylcopper affording a mixture of 
mono‐alkylated and bis‐alkylated product.1 
         The monoalkylation of activated nitriles or tert‐butyl esters by primary alcohols, catalyzed by iridium 
or ruthenium complexes, has been described in the literature.2 
         For  our  part,  we  focused  our  studies  on  the  monoalkylation  of  unactivated  nitriles,  and  more 
particularly  the  acetonitrile  using  primary  alcohols  in  presence  of  iridium  complexes.  The  alkylation  of 
acetonitrile  has  been  achieved  utilizing  aromatic  as  well  as  aliphatic  alcohols  under  micro‐wave  irradiation 
(Scheme 1).3 
 
                                                          Cs 2 CO 3, [IrcodCl] 2
                                  + CH3 CN                                                                CN
                  R      OH                                                                    R
                                                                     MW

                 R = Alk, Ar                                                             up to 26 examples
                                                           Scheme 1 
                                                                  
         The scope and limitations of the alkylation of acetonitrile will be presented and the mechanism of the 
reaction will be discussed. 
 
Acknowledgments/Financial assistance: Sanofi‐Aventis 


1
    For example : D.F. Taber, S. Kong, J. Org. Chem. 1997, 62, 8575 8576; E.J. Corey, I. Kuwajima, Tetrahedron 
Letters 1972, 6, 487489 
2
    For example : for alkylation of activated nitriles : C. Löfberg, R.Grigg, M.A. Whittaker, A. Keep, A. Derrick, J. 
Org. Chem. 2006, 71, 80238027; for alkylation of esters : Y. Iuchi, Y. Obora, Y. Ishii, J. Am. Chem. Soc. 2010, 
132, 25362537
3
   B. Anxionnat, D. Gomez Pardo, G. Ricci, J. Cossy, Angew. Chem. Int. Ed. 2011, submitted
Journées de Chimie Moléculaire 2011                                                                    Chérine BECHARA
23 et 24 mai 2011

             Role of plasma membrane components in the internalization of
                                                 cell-penetrating peptides
                                                     Encadrante : Dr. Sandrine SAGAN
                                             Directrice du Laboratoire : Pr. Solange LAVIELLE
        Laboratoire des Biomolécules, Université Pierre et Marie Curie, CNRS UMR 7203, ENS , 4 place Jussieu, 75252 Paris cedex 05
                                                         Cherine.bechara@upmc.fr

Keywords: cell-penetrating peptide, uptake mechanism, plasma membrane carbohydrates, MALDI-MS
          Cell-penetrating peptides are often short amphipathic sequences rich in basic amino acids. They are
                                                                        1
able to transport biologically active molecules (cargoes) inside cells via two major mechanisms: endocytosis (a
                                                                 2
process that depends on energy) and direct translocation (that results from a direct peptide/membrane
phospholipid interaction).
          The balance between both pathways depends on different parameters, notably the sequence of the
                                 3             4                                                                   5
vector, the nature of the cargo , the cell line and the bond between the peptide and the cargo in a conjugate .
Thus, the final cellular localization of the cargo cannot be predicted. Therefore, it is difficult to rationalize a
specific targeting of a particular intracellular biological activity. In this context, we are interested in studying
the parameters that influence the internalization mechanism and hence the cellular localization of the peptide
vector and/or the conjugate.
          The first molecules that a cell-penetrating peptide meets at the cell-surface are carbohydrates. These
carbohydrates could be partners for internalization through endocytosis or could be useful to concentrate
                                                                                6
locally the peptide and help it to find its way to the lipid membrane below that it can transiently destabilize to
enter. We have now studied the involvement of various cell-surface carbohydrates in the internalization
pathways of different cell-penetrating peptides. The internalization can be followed up and the peptide
                             7
quantified using MALDI-MS . The studied peptide bears a tag composed of four glycine residues together with a
biotin moiety for purification purposes. After incubation with the peptide and washing, a protease is added in
order to detach cells and to degrade the membrane-bound peptide. This avoids overestimating the quantity of
internalized peptide due to the presence of peptides attached to the outer leaflet of the membrane. The cells
are then lysed (0.3% Triton) and boiled, and the cell lysate is incubated with streptavidin-coated magnetic
beads to extract the peptide from the lysate. As mass spectrometry is not a quantitative method per se, an
internal standard is added to the lysis solution. The internal standard is a peptide that has the same sequence
                                                                             2                       1
as the one being quantified except that it bears a tag composed of four H-containing instead of H-containing
glycine residues. This allows the absolute quantification of internalized and membrane-bound peptide. The
peptides are eluted from the streptavidin-coated magnetic beads with a α-cyano-4-hydroxycinnamic acid
matrix and spotted on the MALDI plate. The samples are analyzed by MALDI-TOF MS (positive ion reflector
model).
          The internalization was studied both at 37°C (endocytosis and translocation) and 4°C (translocation), at
different extracellular peptide concentration. In addition, the affinity of these peptides for various
glycoconjugates was determined. The results obtained will be presented and discussed.


Acknowledgments/Financial assistance:
Support for this research is provided by the Ministère de l’Enseignement Supérieur et de la Recherche (PhD fellowship for CB), the
University Pierre and Marie Curie (UPMC- Univ Paris06), ANR (project ParaHP), the CNRS and ENS.


1
 Järver, P.; Mäger, I.; Langel, U. Trends Pharmacol. Sci. 2010, 31, 528-535
2
  Alves, I.D.; Jiao, C.Y.; Aubry, S.; Aussedat, B.; Burlina, F.; Chassaing, G.; Sagan, S. Biochim. Biophys. Acta. 2010, 1798, 2231-2239
3
  Maiolo, J.R.; Ferrer, M.; Ottinger, E.A. Biochim. Biophys. Acta. 2005, 1712, 161-172
4
  Aroui, S.; Brahim, S.; Waard, M.D.; Kenani, A. Biochem. Biophys. Res. Commun. 2010, 391, 419-425
5
  Aubry, S.; Burlina, F.; Dupont, E.; Delaroche, D.; Joliot, A.; Lavielle, S.; Chassaing, G.; Sagan, S. FASEB J. 2009, 23, 2956-2967
6
  Jiao, C.Y.; Delaroche, D.; Burlina, F.; Alves, I.D.; Chassaing, G.; Sagan. S. J. Biol. Chem. 2009, 284, 33957-33965
7 Burlina, F.; Sagan, S.; Bolbach, G.; Chassaing, G. Angew. Chem. Int. Ed. Engl. 2005, 44, 4244-4247
Journées de Chimie Moléculaire 2011                                                                          Hugo Lenormand
23 et 24 mai 2011


Detection and destruction of organophosphorous compounds by hypervalent
                                             stable silylated molecules
                                               Pr. Louis Fensterbank, Dr. Jean-Philippe Goddard
                                                                Pr. Max Malacria
                          Institut Parisien de Chimie Moléculaire (UMR 7201), UPMC, Bat F, 2ème étage, Case 229
                                                     4, Place Jussieu- 75252 Paris cedex 05
                                                      e-mail : hugo.lenormand@upmc.fr

Keywords: pentasilicate, fluoride sensor, organophosphorous, spirosilane

          During these last decades, the terrorist attack risk has increased. For this reason, it is very important
to have efficient methods to detect and destroy chemical warfare. We have taken an interest in
organophosphorous compounds because some of these compounds such as Sarin (1) or Soman (2) are
                                                     1
extremely toxic (DL50 of Sarin < 10 µg/Kg) and stable in water (t1/2 of Soman = 82,5 h at pH = 7). Moreover,
since 1991, these compounds have been considered as weapons of mass destruction by the UN.


                                             O                         O       F
                                                     F
                                                 P                         P
                                                 O                         O
                                                 1                    2
          Our project consists in using a silane, which can cleave the phosphorous-fluorine bond and trap the
fluoride ion generated by the water toxic organophosphorous compounds decomposition. When the silane
                                                                           2
traps the fluoride, a pentasilicate or a hexasilicate is created . The hypervalence modifies the geometry around
the silicon atom. It switches from a tetravalent structure to a trigonal bipyramide structure. We use this
modification to detect the organophosphorous compounds presence. Two reasons prompted us to look further
                                                                                                                   3
into the use in spirosilanes such as compounds 3 and 4 (Figure 1) to make our sensors. First, their
pentasilicalates are stable and have been isolated. Then, bearing an aromatic ring, these silanes give good
responses in UV and fluorescence spectroscopy. Currently, we work on the improvement of the detection limit
of ours sensors by functionalizing of the aromatic ring.

                                                                                      F3 C CF
                                                                                              3
                                                                                     O
                                                         Si
                                                                                    Si
                                                                     F3C           O
                                                                       F 3C


                                                     3                         4
                                 Figure 1 : Spirosilanes used as sensor
Acknowledgments/Financial assistance: D.G.A



1
  H. P. Benschop, L. P. A. De Jong Acc. Chem. Res. 1988, 21, 368-374
2
  C. Chuit, R. J. P. Corriu, C. Reye, J. C. Young, Chem. Rev.1993, 93, 1371–1448
3
  Martin, J. C. J. Am. Chem. Soc. 1985, 107, 6340-6352; Klumpp, G. W. J. Organomet. Chem. 1997, 548, 29-32
Journées de Chimie Moléculaire 2011                                                                               Charlélie BENSOUSSAN 
23 et 24 mai 2011 
 
 
          Efforts towards the synthesis of the fragment C30‐C52 of Amphidinol 3 
                                                                         Sébastien REYMOND 
                                                                             Janine COSSY 
                                                                      ESPCI ParisTech, UMR 7084 
                                                                10 rue Vauquelin, 75231 Paris Cedex 05 
                                                                  charlelie.bensoussan@bde.espci.fr 
 
 
 
Keywords: total synthesis, cross‐couplings, iron catalysis, amphidinol 3. 
 
              Amphidinols are a group of metabolites isolated from the marine dinoflagellates Amphidinium klebsii 
and  Amphidinium  carterae.1  Amphidinol  3  has  emerged  as  an  important  synthetic  target  because  of  its 
antifungal and hemolytic activities2 and its challenging structure composed by a skeleton of 67 carbon atoms 
with 25 stereogenic centers; the absolute stereochemistry has been proposed by Murata and co‐workers using 
J‐based  NMR  spectroscopic  technique,3  but  it  is  still  being  discussed.4    To  date,  no  total  synthesis  of   
amphidinol 3 has been reported in the literature but a number of groups, including our own,5 have published 
the synthesis of advanced fragments. 
              In this presentation, we will present our synthetic efforts towards the C30‐C52 fragment of amphidinol 3 
which contains two highly substituted tetrahydropyran rings and incorporates 15 of the 25 stereocenters. 
 
 
                                                                OH
                                                      HO
                                                     OH                  OH            OH
         67                                53                                43
                                                                                         H                                              O
                                                                                                      OH                        O
                                                                O                 42
                                                52          H       H                                                       O                    OTBS   OTBS
                                                          OH            OH                  O
                                                                                                       OH       TBSO                                                     O
                                                                                                     H                 52               O
                                                                                       HO                                           H       H           H
                                                                                                     OH                         O               OTBS        O
                                                                                                                                                                         O
                                                                                                31                                                          H
                                                           OH            OH OH 30                                                                       O
     1                                     17        19                                                                                                             O
HO
                                      16        18                                                                                                                  30
         OH      OH     OH       OH                       OH            OH
                                                                                                                                                                I


                                       Amphidinol 3                                                                                                                           
 
Acknowledgments/Financial assistance: ANR AMPHI 3 
 

1
  Murata, M.; Matsuoka, S.; Matsumori, N.; Paul, G.K.; Tachibana, K. J. Am. Chem. Soc. 1999, 121, 870.
2
  Houdai, T.; Norsy, N.; Matsumori, N.; Satake, M.; Murata, M. Tetrahedron 2005, 61, 2795.
3
  Matsumori, N.; Kaneno, D.; Murata, M.; Nakamura, H.; Tachibana, K. J. Org. Chem. 1999, 64, 866.
4
  (a) Oishi, T.; Kanemoto, M.; Swasono, R.; Matsumori, N.; Murata, M. Org. Lett. 2008, 10, 5203. (b) Swasono, R.; Kanemoto, M.;
Matsumori, N.; Oishi, T.; Murata, M. Heterocycles 2011, 82, 1359.
5
  (a) Cossy, J.; BouzBouz, S. Org. Lett. 2001, 3, 1451. (b) Cossy, J.; Ferrié, L.; Tsuchiya, T.; Reymond, S.; Kreuzer, T.; Colobert, F.; Serré,
K.; Marko, I. Synlett 2007, 14, 2286. (c) Colobert, F.; Kreuzer, T.; Cossy, J.; Reymond, S.; Tsuchiya, T.; Ferrié, L.; Marko, I.; Jourdain, P.
Synlett 2007, 15, 2351. (d) Cossy, J.; Tsuchiya, T.; Reymond, S.; Kreuzer, T.; Colobert, F.; Marko, I. Synlett 2009, 16, 2706.
Journées de Chimie Moléculaire 2011                                                                Mathieu CYKLINSKY
23 et 24 mai 2011


                            Rearrangement of Acetylenic Epoxides and Aziridines
                                                                    Fabrice CHEMLA
                                                        Franck FERREIRA, Alejandro PEREZ-LUNA
    UPMC-Univ Paris 06, Institut Parisien de Chimie Moléculaire (UMR CNRS 7201), Equipe Synthèse Sélective et Organométalliques, Bâtiment F, 2ème
                                                    étage C.183, 4 place Jussieu, 75252 Paris cedex 5
                                                           email : mathieu.cyklinsky@upmc.fr

Keywords: Silylzincate , 1,2-metalate rearrangement,


            Due to their high electrophilicity, epoxides and aziridines can undergo regio- and stereoselective ring opening
                                                1
with a wide variety of nucleophiles. Our group is more particularly interested in the ring opening of acetylenic
                              2
epoxides and aziridines through a 1,2-metalate rearrangement as follows :




            This rearrangement takes place on organozincates 3 generated by deprotonation of the acetylenic position of
                                                                    3
the corresponding epoxide (X = O) or aziridine (X = NR ) 1 followed by transmetallation of lithium intermediates 2 with
                                                                                2
dialkylzinc species. In this rearrangement, the migration of a R group occurs through a SN2’ mechanism and leads to
propargylzinc 4a which is in metallotropic equilibrium with allenylzinc 4b. The trapping of the mixture of 4a and 4b by
various electrophiles (H2O, aldehydes, ketones...) could lead to a wide variety of propargylic and/or allenic compounds
5a and/or 5b by controlling the stereoselectivity.
                                                                        2
            Our preliminary recent results in this field with R = SiMe2Ph will be presented and discussed.


Acknowledgments/Financial assistance: Ministère de l’enseignement supérieur et de la recherche

1
    Hu, X. E. Tetrahedron 2004, 60, 2701.
2
  (a) Chemla, F.; Bernard, N.; Ferreira, F.; Normant, J. F. Eur. J. Org. Chem. 2001, 17, 3295 (b) Ferreira, F.; Audouin, M.; Chemla, F.; Chem. Eur. J.
2005, 11, 5269 (c) Chemla, F.; Ferreira, F. J. Org. Chem. 2004, 69, 8244.
Journées de Chimie Moléculaire 2011                                                                                                           Guillaume LEFEVRE  
23 et 24 mai 2011 
 
 

        First Evidence of Oxidative Addition of Fe0(N,N)2 to Aryl Halides. This 
    Precondition is not a Guarantee of Efficient Fe‐Catalyzed C‐N Cross‐Couplings 

                                                                     Anny Jutand 
                                                      Dpt de Chimie, Ecole Normale Supérieure 
                                                       24 rue Lhomond – 75231 Paris cedex 5 
                                                              guillaume.lefevre@ens.fr 
                                                                            
Keywords: iron catalysis, C‐N cross‐coupling, cyclic voltammetry, DFT 

     Iron catalysts were introduced in the early 70’s by J. Kochi for promoting the creation of C‐C bonds.1 Latter 
on,  Bolm  shown  that  FeCl3  could  be  used  as  precursor  for  the  catalysis  of  C‐N  cross‐couplings,  until  he 
discovered with Buchwald2 (2009) that such reactions were not catalyzed by pure FeCl3 but by Cu(I) impurities.  

     Some questions arise on the lack of efficiency of iron: is FeCl3 inactive because it is not reduced in situ into 
active FeI, Fe0 or Fe‐II? Even if FeCl3 is reduced in situ, why are the resulting species not efficient catalysts?  

     We report herein electrochemical studies supporting by DFT calculations which establish why iron cannot be 
an efficient catalyst for C‐N cross‐coupling. Even if unprecedented evidence is obtained of oxidative addition of 
Fe0(N,N)2  (N,N = phen, dmeda) to aryl halides with formation of Ar‐Fe‐X(N,N)2, the latter does not lead to the 
expected cross‐coupling product.  Moreover, Fe(III) cannot be reduced in the presence of N‐nucleophiles and 
bases. 3  


                                             E (kcal.mol-1)                  5
                                                                                       4

                                                                                               3
                                                                          6
                                                                                           2
                                                                        Br         1
                                                                     N1       Fe           N4               Br
                                                                                                                       Fe
                                                                        N2
                                                                                  N3
                                                 1
                                                 Fe0(dmeda)2
                                                     PhBr               10.6
                                      0.0

                                                     ISC
                                                                -34.0                                                   Ph
                                                                                                                                       Fe   Br
                                                 3
                                                     Fe0(dmeda)2                                                             Br
                                                        PhBr                                                     N1    Fe    N4
                                                                                                   -103.6
                                                                                                                  N2
                                                                                                                        N3
                                                                N3
                                                           N1
                                                                   N4
                                                                  Fe
                                                                 N2                                              N      N    = dmeda


                                              square planar structure for 1Fe0(dmeda)2



1
  Fürstner, A. Acc. Chem. Res., 2008, 41, 1500-1511
2
  Bolm, C. ; Buchwald, S. Angew. Chem. Int. Ed., 2009, 48, 5586-5587
3
  Lefèvre, G. ; Taillefer, M. ; Adamo, C. ; Ciofini, I. ; Jutand, A. Eur. J. Org. Chem., 2011, in press
Journées de Chimie Moléculaire 2011                                                            Idrissa NDOYE
23 et 24 mai 2011


Isolation and chemical transformation of metabolites from Paraconiothyrium
        variabile, an endophytic fungus of Cephalotaxus harringtonia

                                                    Dr. Bastien Nay, Dr. Soizic Prado
                                                          Prof. Sylvie Rebuffat
 Muséum National d’Histoire Naturelle, Unité Molécules de Communication et Adaptation des Microorganismes (UMR 7245 CNRS-MNHN),
                                               57 rue Cuvier (CP 54), 75005 Paris, France


                                                          e-mail : bnay@mnhn.fr

Keywords: Endophytic fungi, Paraconiothyrium variabile, secondary metabolites, chemical hemisynthesis.


        One of the specific endophytic fungi isolated from the conifer Cephalotaxus harringtonia,
Paraconiothyrium variabile, displayed a significant antagonism against common plant pathogens. To
understand the chemical bases of this antagonism, we undertook the isolation and chemical characterization of
its secondary metabolites, which may be involved in the protection of the plant by the fungus. From the AcOEt
extract of the culture filtrate of P. variabile were isolated four main families of metabolites (scheme 1): α-
tetralones (1-3), isocoumarin (4), isobenzofuran (5) and a cyclodipeptide (6), using different culture conditions.




   Scheme 1: Structures of (1-6) assigned by detailed analysis (NMR spectroscopic and mass data)



        The chemical reactivity of the major metabolite 1 (regiolone) was studied towards biomimetic
transformations, either in oxidative or acidic media. Especially, spirobisnaphtalenes (e.g. 8) were constructed
under acidic conditions (scheme 2). We also hope to obtain regiolone by reductive processes from
commercially available juglone.




                                                                                                                     Natural dimers
                                Scheme 2: Chemical synthesis of selected compounds

Acknowledgments/Financial assistance: French Ambassy at Dakar, Senegal, and Cheikh Anta Diop University of
Dakar for financial support.

Talapatra S.K., Karmacharya, B., Shambhu C., Talapra, D.B. Phytochemistry.1988, 27, 3929-3932
Krohn K., Flörke U., John M., Root N., Ateingröver K., Aust H.J, Draeger S., Schulz B., Antus S., Simonyi M., Zsila F.
Tetrahedron. 57, 2001, 4343-4348
Journées de Chimie Moléculaire 2011                                                                                  Steven Giboulot  
23 et 24 mai 2011 
 
 
    Carbonylation / Carroll Rearrangement Domino Sequence Catalyzed by Palladium 
                                                               Fréderic Liron, Guillaume Prestat 
                                                                         Giovanni Poli  
                                          IPCM, UPMC, UMR CNRS 7201, 4 Place Jusieu, case 183, 75252 Paris Cedex 05 
                                                  e‐mail : Steven.giboulot@upmc.fr, Giovanni.poli@upmc.fr  
 
 
Keywords: Carbonylation, Carroll rearrangement, Palladium catalysis, Pseudo‐domino sequence. 

 
         The  selective  monoallylation  of  ketones  was  realized  via  a  type  I  pseudo‐domino1  sequence  entailing  a 
carbonylation2 step followed by a Carroll rearrangement3, both palladium‐catalyzed. This was achieved by treatment 
of an α‐chloroketone with catalytic amounts of a palladium complex under CO pressure and in the presence of allyl 
alcohol (Scheme 1). 
         We will present our optimization study, as well as the results of the scope and limitations of this process.  Some 
preliminary results of the theoretical study of the catalytic cycle (Scheme 2) will also be presented.  




                                                                                                                               
                                                                              Scheme 1 
                                   O
                                            Cl
                              Ph



                                                                                               CARROLL
                                                   CARBONYLATION                            REARRANGEMENT
                          O
                                          Cl                                  [Pd(0)]                            O    O
                                   [Pd]                                                                                           [Pd]
                     Ph
                                                                                                            Ph            O
                                            CO

                                                                    OH
                                               O    O                                                                     O
                                                               Cl
                                       Ph               [Pd]                  O    O                        CO2 + Ph

                                                                         Ph             O

                                                                              Scheme 2 
 
Acknowledgments/Financial assistance: ANR 
 
                                                                                     
                                                                                     


1
  Poli, G. ; Giambastiani, G. J. Org. Chem. 2002, 67, 9456‐9459. 
2
  Lapidus, A. L.; Eliseev, O. L.; Bondarenko, T. N.; Sizan, O. E.; Ostapenko, E. G.; Beletskaya, I. P. Kinetics and Catalysis 2004, 45, 234‐238.
3
  a) Carroll, M. F. J. Chem. Soc. 1940, 704‐706. b) Chattopadhyay, K.; Jana, R.; Day, V. W.; Douglas, J. T.; Tunge, J. A. Org. Lett. 2010, 12, 3042‐3045. 

								
To top