PhD offer – CIFRE funding superacid group IC2MP UMR 7285-Université de Poitiers / @rtMolecule society « Superelectrophilic activation in superacid: A new route to labelled metabolites» Context: Reactions under superacid conditions1 which allow to develop unprecedented organic processes for direct and original modification of organic compounds, from fine chemicals to polyfunctionalized bioactive molecules, are now widespread reactions in synthetic chemistry. 2 The exploitation of the superacid properties (ability to generate long-lived intermediates, (poly)protonation of substrates and generation of superlectrophiles, 3 CH functionalization, …) led us to develop original synthetic methodologies to deliver in a straightforward way (fluorinated) nitrogen containing compounds coming from high valued synthetic building blocks to bioactive compounds. 4 Since 2005, the group is also engaged in a fruitful collaboration with the society @rtMolecule. @rtMolecule specializes in the custom synthesis of milligram to gram quantities of stable isotope labelled materials (D, 13C, 15N, 18O), metabolites and reference standards (API, impurities, by products,...). Project: Biomimetic reactions have recently become methodologies of choice in the search for new chemical processes. For example, the search for innovative methods to mimic the enzymatic reactions is deeply growing. 5 Many transformations taking place within the enzyme sites can be described as acid-catalyzed reactions. Because of the unique geometry of enzyme active sites and high ionic concentration within them, these reactions are highly dependent on multiple interactions (chelation / protonation). As mentioned by Pr. Olah in his autobiography6 or reported by Thauer and Murphy, 7 these phenomena can be reasonably related to the interactions that take place during the superelectrophilic activation (polyprotonation) of substrates in superacid medium. One of the objectives of the thesis is by using superacid chemistry to develop new methods that mimic the metabolic transformations (and especially hydroxylation). These new biomimetic transformations applied to elaborated bioactive compounds should allow to deliver in a straightforward way, metabolites and key rare analytical standards, making this method a new tool for pharmaceutical industry. Synthetic and efficient routes to the targeted labeled metabolites will also be explored. Applications should include a curriculum vitae with covering letter explaining interest in and suitability for this post. Candidates should also provide names of at least two referees letters for whom they have carried out practical organic chemistry. The closing date for this post is 31 January 2015. Applications should be sent to: [email protected] and [email protected] 1 G. A. Olah, G. K. S. Prakash, A. Molnar, J. Sommer, Superacids (2nd ed), WILEY, New-York, 2009. R. R. Naredla, D. Klumpp, Chem. Rev. 2013, 113, 6905-6948. 3 G. A. Olah, D. Klumpp, Superelectrophiles and their chemistry, John Wiley and Sons, Inc. New-York, 2009. 4 références récentes : (a) B. Métayer, A. Mingot, D. Vullo, C. T. Supuran,* S. Thibaudeau* Chem. Commun. 2013, 49, 6015-6017. (b) G. Compain, A. Martin-Mingot, G. Frapper, C. Bachmann, M-P. Jouannetaud, S. Thibaudeau* Chem. Commun 2012, 48, 5877-5879. (c) G. Compain, K. Jouvin, A. Martin-Mingot, G. Evano*, J. Marrot, S. Thibaudeau * Chem. Commun 2012, 48, 5196-5198. 5 “Biomimetic based applications“, Ed A. George, Intech publisher, 2011. 6 G. A. Olah in A life of magic chemistry: Autobiographical reflexions of a Nobel Prize winner; John Wiley and Sons; New York, 2001. 7 a) A. Berkessel, R. K. Thauer, Angew. Chem. Int. Ed. 1995, 2247-2251. b) M. J. Corr, M. D. Roydhouse, K. F. Gibson, S-Z. Zhou, A. R. Kennedy, A. J. Murphy, J. Am. Chem. Soc. 2009, 17980-17985. 2 Sébastien Thibaudeau / [email protected] IC2MP - UMR 7285 - Université de Poitiers / superacid group – team organic synthesis Bât. B28 - 4 rue Michel Brunet – TSA 51106 - 86073 POITIERS Cedex 09 - FRANCE Tel : +33 (0) 5 49 45 45 88 - http://ic2mp.labo.univ-poitiers.fr/