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.
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.