2. Academic Validation
  3. Protecting-Group-Mediated Diastereoselective Synthesis of C4'-Methylated Uridine Analogs and Their Activity against the Human Respiratory Syncytial Virus

Protecting-Group-Mediated Diastereoselective Synthesis of C4'-Methylated Uridine Analogs and Their Activity against the Human Respiratory Syncytial Virus

  • J Org Chem. 2020 Mar 20;85(6):4267-4278. doi: 10.1021/acs.joc.9b03425.
Christoph Köllmann 1,  Svenja M Sake 2,  Peter G Jones 3,  Thomas Pietschmann 2,  Daniel B Werz 1
Affiliations

Affiliations

  • 1 Technische Universität Braunschweig, Institute for Organic Chemistry, Hagenring 30, 38106 Braunschweig, Germany.
  • 2 Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Feodor-Lynen-Str. 7, 30625 Hannover, Germany.
  • 3 Technische Universität Braunschweig, Institute for Inorganic and Analytical Chemistry, Hagenring 30, 38106 Braunschweig, Germany.
PMID: 32036652 DOI: 10.1021/acs.joc.9b03425
Abstract

Adjusting the protecting group strategy, from an alkyl ether to a bidentate ketal at the carbohydrate backbone of uridine, facilitates a switchable diastereoselective α- or β-C4'/C5'-spirocyclopropanation. Using these spirocyclopropanated nucleosides as key intermediates, we synthesized a variety of C4'-methylated d-ribose and l-lyxose-configured uridine derivatives by a base-mediated ring-opening of the spirocyclopropanol moiety. Investigations of Antiviral activity against the human respiratory syncytial virus were carried out for selected derivatives, showing moderate activity.

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    Product Name
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  • HY-12993
    99.92%, RSV Replication Inhibitor
    RSV