Description du projet
De nouveaux catalyseurs pour soutenir des réactions très spécifiques et un criblage simplifié de potentiels médicaments
La nature ne cesse jamais de nous étonner avec son processus extrêmement efficient et très efficace qui minimise les erreurs. Le fait que des organismes ne disposent que d’une forme de deux molécules quasiment identiques (molécules chirales ou énantiomères) en est un exemple. Les chimistes synthétiques doivent souvent relever le défi de répliquer cette spécificité. Il s’agit d’un véritable casse-tête pour la découverte de médicaments étant donné qu’une forme d’une molécule peut être inactive ou avoir une action indésirable, de sorte que de petites différences peuvent s’avérer très importantes. Le projet PHOTO-ITU, financé par l’UE, associera de nouveaux catalyseurs à la photochimie afin de rapidement générer en une étape des composés chiraux complexes naturels contenant des échafaudages pertinents sur le plan biologique en vue de constituer des bibliothèques de molécules chirales énantiopures.
Objectif
The quest for successful lead candidates in drug discovery has challenged synthetic chemists to develop innovative strategies to rapidly generate screening collections of chiral molecules. In this context, cascade processes provide a powerful tool for rapidly increasing, in one step, structural and stereochemical complexity, while fulfilling the requirements for atom and step economy. The development of asymmetric variants has mainly relied so far on ionic reactivity. PHOTO-ITU seeks to expand the synthetic potential of asymmetric cascade reactions to include the radical reactivity domain. To achieve this goal, we will combine asymmetric organocatalysis and photochemistry, two powerful strategies of modern chemical research with an extraordinary potential for the sustainable preparation of novel molecules. Specifically, we will exploit the unexplored excited-state reactivity of isothiourea-based catalytic intermediates thus merging, for the first time, tertiary amine isothiourea catalysis with asymmetric photochemistry. The resulting photochemical asymmetric radical cascades will rapidly generate, in one single step, architecturally complex chiral natural-like compounds containing biologically relevant heterocyclic scaffolds.
The planned research combines perfectly the fellow’s experience in isothiourea catalysis and the host’s experience in photo-triggered asymmetric processes to develop otherwise unachievable catalytic asymmetric radical cascade reactions. The resulting strategies will be used as an ideal platform for assembling libraries comprising enantiopure chiral small molecules that, along with biological screening carried out in collaboration with an international pharma-company (Bayer AG), will increase the probability of success in identifying drug-candidate structures. The multi-cultural and intersectorial nature of this project will contribute to broaden the fellow’s competencies and will place him in a competitive position for the next career move.
Champ scientifique
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugs
- natural sciencesbiological sciencesbiochemistrybiomolecules
- natural scienceschemical sciencesphysical chemistryphotochemistry
- natural scienceschemical sciencesorganic chemistryheterocyclic compounds
- natural scienceschemical sciencescatalysis
Mots‑clés
Programme(s)
Régime de financement
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
43007 Tarragona
Espagne