4.8 Article

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

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JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 136, 期 16, 页码 5900-5903

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AMER CHEMICAL SOC
DOI: 10.1021/ja502205q

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  1. NIHGMS [R01 GM103558-01]

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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.

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