A General and Enantioselective Approach to Pentoses: A Rapid Synthesis of PSI-6130, the Nucleoside Core of Sofosbuvir

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.