Diastereoselective Synthesis of 2′-Dihalopyrimidine Ribonucleoside Inhibitors of Hepatitis C Virus Replication

[Image: see text] We present a newly developed synthetic route to 2-bromo-2-fluoro ribolactone based on our published 2-chloro-2-fluoro ribolactone synthesis. Stereoselective fluorination is key to controlling the 2-diastereoselectivity. We also report a substantially improved glycosylation reaction...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhou, Longhu, Zhang, Hongwang, Li, Chengwei, De Schutter, Coralie, Sari, Ozkan, Mengshetti, Seema, Zhou, Shaoman, Kasthuri, Mahesh, Coats, Steven J., Schinazi, Raymond F., Amblard, Franck
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8756791/
https://www.ncbi.nlm.nih.gov/pubmed/35036807
http://dx.doi.org/10.1021/acsomega.1c06174
Descripción
Sumario:[Image: see text] We present a newly developed synthetic route to 2-bromo-2-fluoro ribolactone based on our published 2-chloro-2-fluoro ribolactone synthesis. Stereoselective fluorination is key to controlling the 2-diastereoselectivity. We also report a substantially improved glycosylation reaction with both the 2-bromo-2-fluoro and 2-chloro-2-fluoro sugars. These improvements allowed us to prepare 2′-dihalo nucleosides 13 and 14 in an overall 15–20% yield.

Ejemplares similares