Descripción del proyecto
Desbloquear el acceso a nuevas moléculas bioactivas
Los especialistas en química sintética son como niños que juegan con bloques de construcción, quitando y añadiendo piezas para formar todo tipo de arquitecturas de interés. El juego puede resultar frustrante cuando ciertas piezas no se unen correctamente para formar una estructura estable por diversas razones, y en consecuencia, obstruyen el acceso del químico a moléculas novedosas que podrían existir. El proyecto CRAFTMOL, financiado con fondos europeos, pretende ampliar de forma significativa las capacidades de una de las reacciones más importantes utilizadas para crear moléculas cíclicas complejas y diversas a partir de las acíclicas. Con ayuda de métodos computacionales, el equipo se centra en las modificaciones de las moléculas naturales para construir productos naturales bioactivos.
Objetivo
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.
Ámbito científico
Programa(s)
Régimen de financiación
ERC-COG - Consolidator GrantInstitución de acogida
6020 Innsbruck
Austria