1′-Cyano Intermediate Enables Rapid and Stereoretentive Access to 1′-Modified Remdesivir Nucleosides

Tej Poudel, Subhankar Panda, Moyosore Orimoloye, Pooja V Hegde, Courtney C. Aldrich

Research output: Contribution to journalArticlepeer-review

Abstract

While biochemical, structural, and computational studies have shown the importance of remdesivir's C1′-substituent in its perturbation of SARS-CoV-2 RdRp action, we recognized the paucity of methods to stereoselectively install substituents at this position as an obstacle to rigorous explorations of SAR and mechanism. We report the utilization of an anomerically pure 1′-cyano intermediate as an entry point to a chemically diverse set of substitutions, allowing for 1′diversification while obviating the need for the tedious separation of anomeric mixtures.

Original languageEnglish (US)
Pages (from-to)14452-14462
Number of pages11
JournalJournal of Organic Chemistry
Volume87
Issue number21
DOIs
StatePublished - Nov 4 2022

Bibliographical note

Funding Information:
This research was supported by a grant from the NIH (AI136445) to C.C.A. The authors would like to thank Dr. Victor G. Young, Jr., from the Department of Chemistry, University of Minnesota, for X-ray crystallographic analysis.

Publisher Copyright:
© 2022 American Chemical Society. All rights reserved.

PubMed: MeSH publication types

  • Journal Article

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