One-Flow, Multistep Synthesis of Nucleosides by Brønsted Acid-Catalyzed Glycosylation

Authors

  • Dr. Adam Sniady,

    1. Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA 02139 (USA), Fax: (+1) 617-324-0253
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  • Dr. Matthew W. Bedore,

    1. Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA 02139 (USA), Fax: (+1) 617-324-0253
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  • Prof. Dr. Timothy F. Jamison

    Corresponding author
    1. Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA 02139 (USA), Fax: (+1) 617-324-0253
    • Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA 02139 (USA), Fax: (+1) 617-324-0253
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  • This work was supported by the Novartis-MIT Center for Continuous Manufacturing. We would like to thank Dr. Damien Webb (MIT) and the members of the Novartis team for stimulating discussions, in particular Dr. Gerhard Penn, Dr. Berthold Schenkel, Dr. Thierry Schlama, Dr. Mike Girgis, and Dr. Oljan Repic.

Abstract

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Nucleosides in flow: A general, scalable method of Brønsted acid-catalyzed nucleoside formation is described. Because of the high reaction temperatures readily available to the flow reaction format, mild Brønsted acids, particularly pyridinium triflates, can be used. A one-flow multistep synthesis of unprotected nucleosides is also reported (see scheme).

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