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

作者:Peifer Manuel; Berger Raphaelle; Shurtleff Valerie W; Conrad Jay C; MacMillan David W C*
来源:Journal of the American Chemical Society, 2014, 136(16): 5900-5903.
DOI:10.1021/ja502205q

摘要

An efficient route towards biologically relevant pentose derivatives is described. The de novo synthetic strategy features an enantioselective alpha-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.

  • 出版日期2014-4-23