Descrizione del progetto
Nuovi catalizzatori sostengono reazioni altamente specifiche e screening ottimizzati per farmaci potenziali
La natura non smette mai di sorprenderci con le sue trasformazioni estremamente efficienti e altamente efficaci che riducono al minimo gli errori. Un esempio è il fatto che gli organismi hanno solo una forma di due molecole quasi identiche (molecole chirali o enantiomeri). Spesso, i chimici sintetici devono affrontare il problema di replicare tale specificità. Ciò complica le cose per la scoperta di farmaci poiché una data forma di una molecola può essere inattiva o avere funzioni indesiderate; pertanto, anche le minime differenze sono importanti. Il progetto PHOTO-ITU, finanziato dall’UE, combinerà nuovi catalizzatori con la fotochimica per creare rapidamente in un singolo passaggio composti complessi analoghi a quelli chirali presenti in natura che contengono substrati rilevanti a livello biologico utili ad assemblare archivi di molecole chirali enantiopure.
Obiettivo
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.
Campo scientifico
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugs
- natural sciencesbiological sciencesbiochemistrybiomolecules
- natural scienceschemical sciencesphysical chemistryphotochemistry
- natural scienceschemical sciencesorganic chemistryheterocyclic compounds
- natural scienceschemical sciencescatalysis
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
43007 Tarragona
Spagna