title: A general and enantioselective approach to pentoses: a rapid synthesis of PSI-6130, the nucleoside core of sofosbuvir.
abstract: An efficient route towards biologically relevant pentose derivatives is described. The de novo synthetic strategy features an enantioselective α-oxidation reaction enabled by a chiral amine in conjunction with copper(II) catalysis. A subsequent Mukaiyama aldol coupling allows for the incorporation of a wide array of modular two-carbon fragments. Lactone intermediates accessed via this route provide a useful platform for elaboration, as demonstrated by the preparation of a variety of C-nucleosides and fluorinated pentoses. Finally, this work has facilitated expedient syntheses of pharmaceutically active compounds currently in clinical use.
authors.affiliation: Merck Center for Catalysis at Princeton University , Princeton, New Jersey 08544, United States.
authors.forename: Manuel
authors.initials: M
authors.lastname: Peifer
authors.forename: Raphaëlle
authors.initials: R
authors.lastname: Berger
authors.forename: Valerie W
authors.initials: VW
authors.lastname: Shurtleff
authors.forename: Jay C
authors.initials: JC
authors.lastname: Conrad
authors.forename: David W C
authors.initials: DW
authors.lastname: MacMillan
mesh_terms: D060326:Chemistry Techniques, Synthetic; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D007700:Kinetics; D010429:Pentoses / Q000138:chemical synthesis* / Q000737:chemistry*; D000069474:Sofosbuvir; D013237:Stereoisomerism; D013379:Substrate Specificity; D014542:Uridine Monophosphate / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D010429:Pentoses; C504520:2'-deoxy-2'-fluoro-2'-C-methylcytidine; D003841:Deoxycytidine; D014542:Uridine Monophosphate; D000069474:Sofosbuvir