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

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...

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Bibliographic Details
Published in:Journal of organic chemistry 2020-03, Vol.85 (6), p.4267-4278
Main Authors: Köllmann, Christoph, Sake, Svenja M, Jones, Peter G, Pietschmann, Thomas, Werz, Daniel B
Format: Article
Language:English
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Summary: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.
ISSN:0022-3263
1520-6904
DOI:10.1021/acs.joc.9b03425