Description du projet
Cyclisation des terpènes de la tête à la queue: de nouveaux catalyseurs contrôlent la conformation du substrat
Les terpènes constituent une famille de composés bioactifs naturels, qui a joué un rôle déterminant dans la mise au point de médicaments susceptibles de sauver des vies. Il s’agit pour la plupart de terpènes cycliques, formés dans la nature par cyclisation des terpènes avec liaison tête-queue à l’aide d’enzymes. Toutefois, la mise au point de catalyseurs à cet effet représente un défi de taille. Le projet TERPENECAT, financé par le CER, entend bien le relever. Il vise à développer une nouvelle classe de catalyseurs auto-assemblés dont les sites actifs peuvent être modifiés et qui sont capables de contrôler la conformation du substrat pour assurer la sélectivité du processus de cyclisation. En utilisant ces catalyseurs, le projet espère débloquer la synthèse d’autres terpènes à usage médicamenteux qui sont actuellement inaccessibles.
Objectif
Nature is a rich source of biologically active molecules, among which the largest and most diverse group of natural products are terpenes. Essential drugs like the cancer medication taxol/paclitaxel or the malaria drug artemisinin belong to the terpene family. They are efficiently formed in nature through a so-called tail-to-head terpene cyclization. Chemists are not able to mimic this process with man-made catalysts. This proposal aims at closing this significant research gap by utilizing supramolecular chemistry. Learning how to design such complex catalysts will not only enable us to mimic natural enzymes, but to enter uncharted territory of terpene chemistry.
The main objective is the development of selective catalysts for terpene cyclizations. This certainly poses the greatest challenge within this proposal. Therefore, two independent work packages were devised to tackle this challenge. A novel class of self-assembled catalysts will be developed which are able to control the conformation of the substrate, thereby allowing for selectivity in the cyclization process. The active site of these catalysts can be modified to selectively produce the desired terpene product. Additionally, dynamic covalent chemistry will be employed to construct covalent catalyst structures.
As the second objective, this proposal aims to greatly expand the natural variety of terpenes by utilizing unnatural terpene cyclization precursors. Utilizing the catalysts developed from objective 1, unprecedented artemisinin drug derivatives, which are not accessible via other routes, will be synthesized.
This project will provide catalysts which are able to predictably constrain the conformation of the substrate. Such control is not possible with state-of-the-art catalyst systems. Therefore, I anticipate that this project will open up new horizons in the fields of catalysis and organic synthesis.
Champ scientifique
- medical and health scienceshealth sciencesinfectious diseasesmalaria
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugs
- medical and health sciencesclinical medicineoncology
- natural scienceschemical sciencescatalysis
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
Programme(s)
Thème(s)
Régime de financement
ERC-STG - Starting GrantInstitution d’accueil
4051 Basel
Suisse