Descripción del proyecto
Nuevos catalizadores permiten reacciones muy específicas y un cribado optimizado para descubrir posibles fármacos
La naturaleza no deja de sorprendernos con su tratamiento extremadamente eficiente y muy eficaz que minimiza la presencia de errores. El hecho de que los organismos solo tengan una forma de dos moléculas casi idénticas (las moléculas quirales o enantiómeros) es uno de estos ejemplos. Los especialistas en química sintética suelen enfrentarse al reto de reproducir dicha especificidad. Esto dificulta el descubrimiento de fármacos, ya que la forma de una molécula puede estar inactiva o tener una actividad inapropiada, por lo que las pequeñas diferencias acaban siendo muy importantes. El proyecto PHOTO-ITU, financiado con fondos europeos, combinará nuevos catalizadores y la fotoquímica para generar rápidamente, en un solo paso, complejos compuestos quirales naturales que contienen andamios pertinentes desde el punto de vista biológico para reunir bibliotecas de moléculas quirales enantiopuras.
Objetivo
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.
Ámbito científico
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugs
- natural sciencesbiological sciencesbiochemistrybiomolecules
- natural scienceschemical sciencesphysical chemistryphotochemistry
- natural scienceschemical sciencesorganic chemistryheterocyclic compounds
- natural scienceschemical sciencescatalysis
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Programa(s)
Régimen de financiación
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinador
43007 Tarragona
España