Arnaud Martel

Carte de visite

Arnaud Martel

1:I.U.T LE MANS - Département Chimie, 2:U.F.R SCIENCES et TECHNIQUES - IMMM-Institut des Molécules et Matériaux du Mans

Adresse : Av. Olivier Messiaen,72085 LE MANS CEDEX 9
France

Site web :https://orcid.org/0000-0002-0126-1654

Description

FORMATION ET EXPERIENCES PROFESSIONNELLES

Depuis Sep 2013 : Professeur des Universités, IUT Le Mans

Sep 2004-Sep 2013 Maître de conférences, IUT du Mans.

Dec 2010 Habilitation à diriger les recherches, Chimie, Université du Maine, Le Mans.

Avril 2003-Septembre 2004 Université d’Uppsala (Suède), Chercheur post-doctorant dans l’équipe du Dr. Henrik Ottosson. Bourse Marie Curie.

Etude théorique assistée d’outils de modélisation moléculaire, puis synthèse de 2-silenolates chiraux.

Mars 2002-Mars 2003 ICOA (Institut de chimie organique et analytique) Université d’Orléans, Chercheur Post-doctorant. Financement industriel.

Recherche sur un projet industriel au sein de l’équipe du Pr. Guillaumet. Synthèse de méthylènemalonates.

Sep 2001 Doctorat Chimie Fine, Chimie Organique (mention très honorable), Université du Maine, Le Mans.

Titre : Hétérocycloaddition stéréocontrôlées d’éthers d’énols de cétones cycliques - Accès aux 9-décanolides.

1997 D.E.A Chimie Fine : Élaboration de biomolécules et matériaux organiques (Modules optionnels : Matériaux organiques, Théorie orbitalaire et mécanismes réactionnels ; mention bien), Université du Maine cohabilité avec l’Université de Nantes.

1996 Maîtrise de Chimie (Module optionnel : Physicochimie des polymères, mention assez-bien), Université du Maine, Le Mans.

1994 D.U.T Chimie, IUT Le Mans, Université du Maine.

 

ENSEIGNEMENTS

IUT Chimie Le Mans.

Disciplines enseignées : Chimie Analytique, Génie Chimique, Informatique, Modélisation Moléculaire.

Faculté des Sciences.

Master 1 – Module liaisons.

 

RESPONSABILITES ET MANDATS

- Responsable de la licence professionnelle Analyse chimique et contrôle des matériaux

- élu au conseil d'administration de l'université

- élu au conseil d'unité de l'IMMM

Activité

Synthèse totale convergente de la kidamycine

 

Membres intervenants:  Gilles Dujardin, Christine Saluzzo, Stéphane Guillarme, Arnaud Martel

 

Collaboration : Sylvain Collet (Porteur), Jacques Lebreton, Monique Mathé-Alainmat (CEISAM, Nantes); Bertrand Carboni, François Carreaux (Institut des sciences chimiques de Rennes).

 

Le projet ANR KidamySyn, proposé sur la base d’une collaboration entre 3 équipes de 3 laboratoires distincts (Nantes, Rennes et Le Mans) consiste à effectuer la première synthèse totale d’un membre de la famille des pluramycines : la kidamycine.

 

L’objectif principal du projet porte sur la synthèse de la kidamycine et nécessitera la synthèse d’un diénophile porteur de deux fonctions C-glycosides afin de l’engager dans une réaction clé de cycloaddition avec les diènes développés précédemment. Les approches synthétiques rapportées dans la littérature récente mentionnent les difficultés rencontrées dans l’installation stéréosélective des deux motifs glycosidiques par glycosylation directe, plus particulièrement pour celle de la L-vancosamine. Nous proposons quant à nous une stratégie basée sur la C-glycosylation directe avec la D-angolosamine, suivie de l’introduction du glycal de la vancosamine. La configuration alpha requise sur la L-vancosamine sera contrôlée lors de l’étape clé précédant la cycloaddition [4+2] qui permet le couplage des partenaires diènes et diénophiles développés précédemment. Un nombre limité d’étapes d’aménagements fonctionnels doit permettre d’accéder à la molécule finale.

 

Cette approche convergente pourra par la suite être appliquée à la synthèse d’autres membres de la famille pluramycine et d’analogues en vue d’établir un profil structure-activité et orienter de futures recherches vers la synthèse molécules plus actives.

Synthèse énantiosélective d’oxaprolines et d’amino acides disubstitués via CD-1,3 asymétrique de cétonitrones polyfonctionnelles.

 

Membres intervenants : Khalid B. Selim, Xiaofei Zhang, Kawther Ben Ayed, Mathieu Laurent, Arnaud Martel, Gilles Dujardin

Une nouvelle impulsion à notre thématique « Hétérocycloadditions » a été donnée en développant un nouveau type de cétonitrones polyfonctionnelles dans des réactions CD-1,3 asymétriques vis à vis d’éthers vinyliques (1) ou d’énals (3) et créatrices de centres quaternaires à haute densité fonctionnelle.

Ces hétérocycles permettent un accès à des dérivés inédits de b3,b3-aminoacides (2) (aspartiques notamment) en vue d’appli-cations en synthèse de composés peptidomimétiques ou pour l’accès à des oxaprolines à forte contrainte stérique pour des applications en organocatalyse.

Ce travail financé par l’ANR (ANR « Oxaprol ») vise également à rationaliser les diastéréo- et énantiosélectivités observées et à étudier les mécanismes des CD-1,3 sous catalyse asymétrique avec l’aide de modélisation DFT.

 

 

Publications

  • Enantioselective 1,3-DC reactions of C-Carboxy Ketonitrones and Enals with MacMillan catalyst: Evidence of a non-concerted mechanism (Arnaud Martel - Ben Ayed - K.; Laurent - M. Y.; Martel - A.; Selim - K. B.; Abid - S.; Dujardin - G., European Journal of Organic Chemistry, ASAP)

    Highly diastereo- and enantioselective 1,3-dipolar cycloadditions between functional ketonitrones and β-substituted enals are promoted by organocatalysis with the imidazolidinium catalyst of MacMillan. Study of the scope of the reaction shows that high selectivities are conserved by varying the N-protecting group or the ester function. However it is sensitive to sterical interaction with the C-substituent of the nitrone. Reaction proceeds in all cases with a high exo selectivity. In most cases, a third diastereomer, not compatible with a concerted mechanism, was observed, although in minute amount. DFT calculations evidence that the cycloaddition proceeds in a non-concerted fashion by a first oxa Michael-type addition of the nitrone to the double bond followed by a cyclization. This mechanism explains the formation of the observed minor diastereomers. In addition, the diastereo- and enantioselectivities of the reaction were shown to be intermediately thermodynamically controlled and the diastereomeric ratio is modulated by the kinetics of iminium hydrolysis.

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  • Regio-, and Stereoselective Synthesis of Polysubstituted Oxazolo[3,2-d][1,4]oxazepin-5(3H)ones via a Domino oxa-Michael/aza-Michael/Williamson Cycloetherification Sequence.

    Regio-, and Stereoselective Synthesis of Polysubstituted Oxazolo[3,2-d][1,4]oxazepin-5(3H)ones via a Domino oxa-Michael/aza-Michael/Williamson Cycloetherification Sequence. (Arnaud Martel - El Bouakher - A.; Tasserie - J.; Le Goff - R.; Lhoste - J.; Martel - A.; Comesse - S., J. Org. Chem. 2017, 82 (11), 5798-5809.)

    The access to new oxazolo[3,2-d][1,4]oxazepin-5(3H)-ones starting from α-bromoamido alcohols and Michael acceptors under mild conditions is presented. This domino process proved to be chemo-, regio-, and stereoselective and allows the formation of a large diversity of highly functional 7-membered rings in good yields up to 95%. The complete shift of the regioselectivity of the intermediate enolate from a C–C to a C–O bond formation, contrary to the already known alkylations of such ambident nucleophiles, is mostly triggered by steric effects. The last step of the sequence was modeled by DFT giving some important insights for this C–C vs C–O bond shift.

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  • Enantioselective Access to Robinson Annulation Products and Michael Adducts as Precursors

    Enantioselective Access to Robinson Annulation Products and Michael Adducts as Precursors (Arnaud Martel - Gallier - F.; Martel - A.; Dujardin - G, Angew. Chem., Int. Ed. 2017, 56 (41), 12424-12458.)

    The Robinson annulation is a reaction that has been useful for numerous syntheses since its discovery in 1935, especially in the field of steroid synthesis. The products are usually obtained after three consecutive steps: the formation of an enolate (or derivative), a conjugate addition, and an aldol reaction. Over the years, several methodological improvements have been made for each individual step or alternative routes have been devised to access the Robinson annulation products. The first part of this Review outlines the most relevant developments towards the formation of monocarbonyl-derived Robinson annulation products (MRA products, MRAPs) and activated monocarbonyl-derived Robinson annulation products (AMRA products, AMRAPs). The following sections are then devoted to the diastereoselective and enantioselective synthesis of these products, while the last section describes the enantiomeric resolution of racemic mixtures.

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  • Oxa–diketopiperazines: Access and Conformational Analysis of Potential Turn Inducers (Arnaud Martel - Dr. Mathéo Berthet - Aurélien Lebrun - Prof. Arnaud Martel - Thomas Cheviet - Prof. Jean Martinez and Dr. Isabelle Parrot, ChemistrySelect 2017, 2 (21), 5824-5827.)

    An improvement of the 1,2,5-oxadiazine-3,6-diones (Oxd) synthesis and reactivity is described in this paper. The methodology has been successfully applied to produce a library of this poorly studied scaffold, which can be considered as an oxa-diketopiperazine (oxa-DKP). Significantly, the first crystal structures of oxa-DKP were obtained and compared to the diketopiperazine ring. Finally, a straightforward procedure concerning the coupling of various amino acids with oxa-DKP heterocycles to afford original peptidomimetics was reported. The conformational analysis realized on di- and tripeptide analogs revealed that the oxa-DKP skeleton exhibited remarkable β-turn inducer properties.

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  • Synthesis of Oxazolidin-4-ones: Domino O-Alkylation/Aza-Michael/Intramolecular Retro-Claisen Condensation

    Synthesis of Oxazolidin-4-ones: Domino O-Alkylation/Aza-Michael/Intramolecular Retro-Claisen Condensation (Arnaud Martel - Abderrahman El Bouakher - Ronan Le Goff - Jordan Tasserie - Jérôme Lhoste - Arnaud Martel - and Sébastien Comesse, 2016)

    An original and rapid domino reaction for access to oxazolidin-4-ones is presented. Simply by heating α-bromoamido alcohol in the presence of KNaCO3 and water with readily prepared Michael acceptors, an unprecedented molecular rearrangement is generated. This new methodology enables the hitherto unreported synthesis of functionalized oxazolidin-4-ones. The process was proved to be compatible with a wide variety of substrates, and high regioselectivities were achieved.

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  • Practical and Cost-​Effective Method for the Synthesis of Bicyclo[2.2.2]​octane-​1,​4-​dicarboxylic Acid (Arnaud Martel - Le Marquer Nicolas - Laurent Mathieu Yves, 2015)

    A short and efficient synthesis of bicyclo[2.2.2]​octane-​1,​4-​dicarboxylic acid involving the formation of a semicarbazone is developed, and a reproducible protocol for the redn. of this semicarbazone is described. The use of microwaves significantly shortens the duration of the sequence to the diacid compared to the previously described synthetic method. In addn., by shifting from the use of large amts. of Raney nickel to a solid-​phase process, both the safety and cost are improved notably.

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  • [3+2] Route to quaternary oxaprolinol derivatives as masked precursors of disubstituted β3,​β3-​amino aldehyde (Arnaud Martel - Shpak-Kraievskyi Pavlo - Mankou Makaya Amelle - Beauchard Anne - Laurent Mathieu Y. - Dujardin Gilles, 2015)

    Bicyclic isoxazolidines displaying one or two quaternary stereocenter(s) were formed starting from functional cyclic ketonitrones equipped with a Ph glycinol chiral auxiliary. The products were engaged in stereocontrolled 1,​3-​dipolar cycloaddn. reactions with a range of electron-​rich and electron-​poor dipolarophiles. A new reductive removal of the Ph glycinol chiral auxiliary was introduced and was shown to afford chemoselectively a quaternary isoxazolidine deriv. (of oxaprolinol-​type) without cleaving the N-​O isoxazolidine bond. Keeping the aldehyde function masked as a cyclic pseudo-​acetal, the liberated oxy-​amine function was shown to be available for a pseudo-​peptide coupling with various N-​protected amino acids. The isoxazolidine ring was opened by a reductive N-​O bond cleavage, giving a pseudo-​dipeptide that was C-​terminated with an aldehyde function.

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  • Simple Access to Highly Functional Bicyclic gamma- and delta-Lactams: Origins of Chirality Transfer to Contiguous Tertiary/Quaternary Stereocenters Assessed by DFT. (Arnaud Martel - Le Goff Ronan - Sanselme Morgane - Lawson Ata Martin - Daich Adam - Comesse Sebastien, 2015)

    This paper describes the synthesis of both polysubstituted oxazolo-​pyrrolidinones and -​piperidinones by a domino process. The methodol. is based on the reaction between hydroxyl halogenoamides and Michael acceptors, which leads efficiently to bicyclic lactams. The process is compatible with unsym. electron-​withdrawing groups on the Michael acceptor, which allows the formation of two contiguous and fully controlled tertiary and quaternary stereocenters. In the case of tetrasubstituted Michael acceptors, two adjacent quaternary stereocenters are formed in good yield. Starting from (R)​-​phenylglycinol derived amides results in the formation of enantio-​enriched bicyclic lactams in low to good yields and with high levels of stereoselectivity, thus greatly increasing the scope and interest of this strategy. The origins of chirality transfer and diastereoselectivity were studied by DFT calcns. and have been attributed to a kinetic control in one of the last two steps of the reaction sequence. This selectivity is dependent upon both the substituents on the Michael acceptor and the sodium cation chelation.

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  • Asymmetric access to α-​substituted functional aspartic acid derivatives by a [3+2] strategy employing a chiral dienophile (Arnaud Martel - Ben Ayed Kawther - Beauchard Anne - Poisson Jean-Francois - Py Sandrine - Laurent Mathieu Y. - Ammar Houcine - Abid Souhir - Dujardin Gilles, 2014)

    Enantiopure vinyl ethers of Stericol underwent diastereoselective thermal 1,​3 dipolar cycloaddns. with N-​benzyl, N-​benzhydryl, and N-​PMB aspartate ester nitrones. Chemoselective N-​debenzylation of the resulting cycloadducts afforded diastereomerically and enantiomerically pure cryst. NH-​isoxazolidine, the abs. configuration of which was established by X-​ray crystallog. N-​Protection and N-​O cleavage of this isoxazolidine gave enantioenriched quaternary aspartate derivs. bearing functionalized side chains.

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  • Asymmetric Synthesis of α,α-Disubstituted Amino Acids by Cycloaddition of (E)-Ketonitrones with Vinyl Ethers

    Asymmetric Synthesis of α,α-Disubstituted Amino Acids by Cycloaddition of (E)-Ketonitrones with Vinyl Ethers (Arnaud Martel - Xiaofei Zhang - Pascale Cividino - Jean-François Poisson - Pavlo Shpak-Kraievskyi - Mathieu Y. Laurent - Gilles Dujardin - and Sandrine Py, 2014)

    Original acyclic (E)-α,α-dialkylketonitrones bearing a chiral auxiliary on their nitrogen atom were synthesized and successfully employed for the asymmetric synthesis of α,α-disubstituted amino acids using regio- and stereocontrolled 1,3-dipolar cycloaddition reactions with vinyl ethers. N-Glycosyl chiral auxiliaries were found to provide excellent exo- and π-facial stereocontrol. The obtained enantiopure cycloadducts were selectively transformed into functional α,α-disubstituted amino acids and related β-peptides through the highly regioselective opening of an intermediate quaternary anhydride.

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  • Enantioselective Ruthenium-Catalyzed 1,3-Dipolar Cycloadditions between C-Carboalkoxy Ketonitrones and Methacrolein: Solvent Effect on Reaction Selectivity and Its Rational

    Enantioselective Ruthenium-Catalyzed 1,3-Dipolar Cycloadditions between C-Carboalkoxy Ketonitrones and Methacrolein: Solvent Effect on Reaction Selectivity and Its Rational (Arnaud Martel - Khalid B. Selim - Mathieu Y. Laurent - Jérôme Lhoste - Sandrine Py - and Gilles Dujardin, 2014)

    A catalytic 1,3-dipolar cycloaddition between carboalkoxy ketonitrones and methacrolein under the effect of chiral ruthenium Lewis acid (R,R-1) was developed with high regio-, diastereo-, and enantiocontrol. The diastereochemical outcome of the cycloaddition reaction is marked by a significant solvent effect, and a divergent endo or exo control can be tuned by an appropriate choice of both the solvent and the N- and O-substituents of the ketonitrone. A rationale of the solvent effect, based on the computational study of the interactions between the methacrolein–Ru complex and its counteranion (SbF6–), is proposed to explain the selectivities obtained.

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  • Organocatalytic enantio- and diastereoselective 1,3-dipolar cycloaddition between alanine-derived ketonitrones and E-crotonaldehyde: efficiency and full stereochemical studies

    Organocatalytic enantio- and diastereoselective 1,3-dipolar cycloaddition between alanine-derived ketonitrones and E-crotonaldehyde: efficiency and full stereochemical studies (Arnaud Martel - Khalid B. Selim - Anne Beauchard - Jérôme Lhoste - Mathieu Y. Laurent - Gilles Dujardin, 2012)

    Highly enantio- and exo-selective 1,3-dipolar cycloadditions of alanine-derived ketonitrones to E-crotonaldehyde could be realized in a good yield by the use of a chiral imidazolidinone salt without the addition of water. The origin of the stereoselectivity in the reaction was discussed and the absolute configuration of the cycloadduct determined unambiguously.

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  • Domino Process Optimized via ab Initio Study for an Alternative Access to Bicyclic Lactams

    Domino Process Optimized via ab Initio Study for an Alternative Access to Bicyclic Lactams (Arnaud Martel - Sébastien Comesse - Adam Daïch, 2011)

    A totally new acid-free domino process to access highly functionalized bicyclic γ- and δ-lactams starting from commercially available and inexpensive ethoxymethylene derivatives is reported. Mechanisms elucidated by computational calculations led to new reaction conditions that boosted the yields up to 3.5 times higher.

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  • A Convergent Hetero-​Diels-​Alder Strategy for Asymmetric Access to a Lactone Containing Two Lipidic Chains (Arnaud Martel - Vu Cong S. - Guisot Nicolas - Guillarme Stephane - Dujardin Gilles - Pipelier Muriel - Dubreuil Didier - Saluzzo Christine, 2012)

    Eu(fod)​3-​catalyzed hetero-​cycloaddn. of chiral β-​alkyl-​N-​vinyl-​1,​3-​oxazolidin-​2-​ones with a hetero-​diene bearing a lipidic chain led to hetero-​cycloadducts in high yield with excellent endo and facial selectivities. An original lipidic lactone I, a potent precursor of a ceramide analog, was obtained in seven steps from the adduct in a convergent manner after appropriate functionalization.

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