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Enantioselective synthesis of quaternary 3,4-dihydroisoquinolinones via Heck carbonylation reactions: development and application to the synthesis of Minalrestat analogues

Minalrestat and its analogues represent structurally novel aldose reductase inhibitors, and the asymmetric synthesis of such pharmaceutically privileged molecules has not been reported yet. We have developed a palladium-catalyzed enantioselective intramolecular carbonylative Heck reaction by using f...

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Detalles Bibliográficos
Autores principales: Cheng, Cang, Wan, Bin, Zhou, Bo, Gu, Yichao, Zhang, Yanghui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977551/
https://www.ncbi.nlm.nih.gov/pubmed/32015808
http://dx.doi.org/10.1039/c9sc03406d
Descripción
Sumario:Minalrestat and its analogues represent structurally novel aldose reductase inhibitors, and the asymmetric synthesis of such pharmaceutically privileged molecules has not been reported yet. We have developed a palladium-catalyzed enantioselective intramolecular carbonylative Heck reaction by using formate esters as the source of CO, which represents the first enantioselective synthesis of quaternary 3,4-dihydroisoquinolines. The reaction provides a facile and efficient method for the synthesis of enantiopure nitrogen-containing heterocyclic compounds bearing an all-carbon quaternary stereocenter. The reaction has been successfully applied to the first asymmetric synthesis of Minalrestat analogues.