Modified C-nucleosides have proven to be enormously successful as chemical probes to understand fundamental biological processes and as small-molecule drugs for cancer and infectious diseases. Historically, the modification of the glycosyl unit has focused on the 2′-, 3′-, and 4′-positions as well as the ribofuranosyl ring oxygen. By contrast, the 1′-position has rarely been studied due to the labile nature of the anomeric position. However, the improved chemical stability of C-nucleosides allows the modification of the 1′-position with substituents not found in conventional N-nucleosides. Herein, we disclose new chemistry for the installation of diverse substituents at the 1′-position of C-nucleosides, including alkyl, alkenyl, difluoromethyl, and fluoromethyl substituents, using the 4-amino-7-(1′-hydroxy-d-ribofuranosyl)pyrrolo[2,1-f][1,2,4]triazine scaffold as a representative purine nucleoside mimetic.
Bibliographical noteFunding Information:
This research was supported by a grant from the NIH (AI136445) to C.C.A. We would like to thank Dr. Victor G. Young, Jr. from the Department of Chemistry, University of Minnesota for X-ray crystallographic analysis. We would also like to thank collaborators from Waters Corporation (including Marguerite Arechederra, Matthew Lauber, and Erica Manandhar) for their donation of HPLC columns in support of this project.
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural