Project description
Novel catalysts support highly specific reactions and streamlined screening for potential drugs
Nature never ceases to amaze us with its extremely efficient and highly effective processing that minimises errors. The fact that organisms have only one form of two nearly identical molecules (chiral molecules or enantiomers) is one example. Synthetic chemists are often challenged to replicate this specificity. This causes headaches for drug discovery as one form of a molecule may be inactive or have undesirable activity, so small differences matter in a big way. The EU-funded PHOTO-ITU project will combine novel catalysts and photochemistry to rapidly generate in a single step complex chiral natural-like compounds containing biologically relevant scaffolds to assemble libraries of enantiopure chiral molecules.
Objective
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.
Fields of science
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugs
- natural sciencesbiological sciencesbiochemistrybiomolecules
- natural scienceschemical sciencesphysical chemistryphotochemistry
- natural scienceschemical sciencesorganic chemistryheterocyclic compounds
- natural scienceschemical sciencescatalysis
Keywords
Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
43007 Tarragona
Spain