Descripción del proyecto
Nuevos catalizadores permiten conseguir olefinas tetrasustituidas para el descubrimiento de fármacos
Las olefinas tetrasustituidas, hidrocarburos con dobles enlaces de carbono en los que se han sustituido cuatro hidrógenos por otro átomo o grupo, pueden permitir conseguir de forma directa tanto moléculas biológicas como intermediarios, por lo que son fundamentales en el descubrimiento de fármacos. La metátesis olefínica constituye una ruta eficaz y estereodivergente para obtener olefinas tetrasustituidas. Sin embargo, las reacciones y los catalizadores necesarios para lograr el repertorio deseado de productos plantean múltiples retos. El objetivo del proyecto HISUBMET, financiado por el Consejo Europeo de Investigación, es superar estos retos. Su equipo diseñará un nuevo tipo de catalizadores de molibdeno y tungsteno que se pueden utilizar para promover reacciones eficientes de metátesis de cierre de anillo y metátesis cruzada, que permitirán obtener una amplia variedad de olefinas tetrasustituidas fácilmente modificables. También se desarrollarán otros catalizadores.
Objetivo
Tetrasubstituted olefins are key to drug discovery, and the ability to such entities is a compelling goal. Pioneering studies have led to a number of noteworthy advances by significant shortcomings remain. For example, it is especially challenging to access tetrasubstituted alkenes that contain four sizeable substituents or a F atom and/or a CF3 unit. Most protocols can only afford one of the possible isomers.
Tetrasubstituted alkenes that contain multiple modifiable substituents are particularly attractive, because they can serve as diversification points that lead to a large assortment of desirable compounds. Olefin metathesis offers a strategically distinct, efficient, and stereodivergent route to such entities. Yet, there are only a few reported olefin metathesis reactions that generate a cyclic tetrasubstituted olefin that does not contain two methyl substituents at each carbon (i.e. no stereochemistry). A much smaller number (four cases) are RCM reactions that afford cyclic tetrasubstituted olefins with one modifiable C–Cl bond. All involve a Ru catalyst. However, olefin metathesis reactions that can generate poly-halogenated olefins cannot be effected with a Ru catalyst (rapid decomposition). Only a Mo or a W catalyst must be used, but such complexes do not exist.
We will design a new class of pivoting Mo and W catalysts that can be used to promote efficient RCM and cross-metathesis (CM) reactions that generate a wide range of readily modifiable tetrasubstituted olefins. We will accomplish this by designing catalysts wherein the rotation of the imido and aryloxide ligands is synchronized, so that a proper binding pocket is made available. The expected products, which can serve as versatile diversification points, will contain 2-3 easily modifiable units.
We will also design an entirely new class of cyclic Mo and W catalysts for CM between easily accessible trisubstituted alkenes and polyhalogenated alkenes. A unique feature of these catalysts is that intra
Ámbito científico
Programa(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régimen de financiación
HORIZON-AG - HORIZON Action Grant Budget-BasedInstitución de acogida
67000 Strasbourg
Francia