Synthesis of a Nucleoside Phosphoramidate Prodrug Inhibitor of HCV NS5B Polymerase: Phenylboronate as a Transient Protecting Group

Autor:	Elodie Rosinovsky, Narayan Chaudhuri, Benjamin Alexander Mayes, Christophe Trochet, Steven Mathieu, G. Mark Latham, Alistair Stewart, Adel Moussa, Jie Li, Jeevanandam Arumugasamy, Alan Becker, Erkan Baloglu, F. Patrick McGarry, Jingyang Wang, David Bauer
Rok vydání:	2014
Předmět:	chemistry.chemical_classification Stereochemistry Hepatitis C virus Organic Chemistry Thio Phosphoramidate Prodrug medicine.disease_cause chemistry.chemical_compound chemistry medicine Nucleotide Physical and Theoretical Chemistry Phenylboronic acid Protecting group Nucleoside
Zdroj:	Organic Process Research & Development. 18:717-724
ISSN:	1520-586X 1083-6160
Popis:	A synthetic process for 2′-C-methylcytidine-5′-[2-[(3-hydroxy-2,2-dimethyl-1-oxopropyl)thio]ethyl-N-benzylphosphoramidate], a nucleotide prodrug inhibitor of hepatitis C virus NS5B polymerase, is described. The route developed was demonstrated on 100 g scale and featured the key application of phenylboronic acid as an effective transient means to protect the 2′,3′-hydroxyls of 2′-C-methylcytidine. This synthetic methodology resulted in a reduction in the number of isolations from five to two and an increase in the overall yield by 50% relative to the original unscalable discovery route. The synthesis and characterization of 2′-C-methylcytidine-2′,3′-O-phenylboronate is also provided.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::6560b20a8c693f5283f4af20fa03985c https://doi.org/10.1021/op500042u Zobrazit plný text záznamu