Origin of the selectivity in the ring-closing metathesis step of the synthesis of (−)-callyspongiolide: Formation of fourteen-versus eight-membered rings

In previous work we reported the formal synthesis of the marine macrolide (−)-callyspongiolide through a synthetic approach in which the generation of the key macrocyclic core relies on a ruthenium-catalyzed ring-closing metathesis reaction. However, besides the predicted macrolactone intermediate,...

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Detalles Bibliográficos
Autores: Díaz-Ruiz, Marina, Urbina Teixidor, Aina, Llor Brunés, Núria, Bosch Cartes, Joan, Amat Tusón, Mercedes, Maseras Cuní, Feliu
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2022
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/193700
Acceso en línea:https://hdl.handle.net/2445/193700
Access Level:acceso abierto
Palabra clave:Metàtesi (Química)
Compostos bioactius
Síntesi orgànica
Alcaloides
Metathesis (Chemistry)
Bioactive compounds
Organic synthesis
Alkaloids
Descripción
Sumario:In previous work we reported the formal synthesis of the marine macrolide (−)-callyspongiolide through a synthetic approach in which the generation of the key macrocyclic core relies on a ruthenium-catalyzed ring-closing metathesis reaction. However, besides the predicted macrolactone intermediate, an undesired cyclooctene was observed. We investigate here the mechanism of this critical step through density functional theory calculations. The results indicate that the chemoselectivity is not under kinetic control but ruled by thermodynamics. This conclusion is further confirmed by additional experimental studies.