Descrizione del progetto
Sbloccare l’accesso a nuove molecole bioattive
I chimici sintetici sono come i bambini che giocano con i mattoncini da costruzione, rimuovendo parti e aggiungendone altre per formare ogni sorta di architetture di interesse. Il gioco può diventare frustrante quando alcuni pezzi non si collegano correttamente a formare una struttura stabile per vari motivi, bloccando l’accesso per un chimico a nuove molecole che potrebbero nascere. Il progetto CRAFTMOL, finanziato dall’UE, prevede di espandere in modo significativo le potenzialità di una delle reazioni più importanti utilizzate per costruire molecole cicliche complesse e diverse da quelle acicliche. Supportato da metodi computazionali, l’obiettivo del gruppo di ricercatori è di modificare molecole naturali per la costruzione di prodotti naturali bioattivi.
Obiettivo
Polyene cyclizations belong to the most powerful and fascinating chemical transformations to rapidly assemble molecular architectures. However, the very limited substitution pattern of known substrates and nature’s inability to accommodate heteroatoms or substituents other than methyl restrict molecular diversity, complexity and functionality. CRAFTMOL addresses these limitations by investigating a set of novel heteroatom-substituted and tri/tetrasubstituted polyenes. The participation of these structural units in the cyclization will unlock previously inaccessible reaction pathways and enable efficient, selective and practicable routes to anticancer, anti-inflammatory and antiviral molecules. We will first investigate substrates containing trisubstituted double bonds and explore their behavior in cyclizations involving a transannular/cross-termination step. Realization of this concept will provide a highly modular synthetic platform for the rapid construction of more than 15 bioactive natural products. For the second part, we will explore tetrasubstituted double bonds to realize first-time synthesis of a structurally diverse family of natural products with unique biological activities. We will accomplish these goals by taking advantage of our expertise in total synthesis of complex natural products and modern chemical methodology. The experiments will be guided by computational methods and supported by our high-pressure platform. CRAFTMOL is ground-breaking as it 1) unveils innovative reaction pathways, 2) provides efficient synthetic access to structurally diverse molecular architectures, 3) enables deep-seated structural modifications of natural molecules that are currently inaccessible via fermentation or semi-synthesis. CRAFTMOL will lead to a better understanding of polyene cyclizations, will inspire scientists to develop novel methods for the construction of highly valuable molecules and will therefore advance the entire field of chemical synthesis.
Campo scientifico
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-COG - Consolidator GrantIstituzione ospitante
6020 Innsbruck
Austria