Protecting Group Control of Hydroxyketone-Hemiketal Tautomeric Equilibrium Enables the Stereoselective Synthesis of a 1<i>′</i>-Azido <i>C</i>-Nucleoside
The synthesis of 1<i>'</i>-azido <i>C</i>-nucleosides is described to expand the set of azide-functionalized nucleosides for bioorthogonal applications and as potential antiviral drugs. Lewis acid-promoted azidation of a nucleoside hemiketal resulted in the formation of a tetrazole through a Schmidt reaction manifold. Conformational control to prevent ring-chain tautomerism enabled efficient 1<i>'</i>-azidation with complete β-diastereoselectivity. The unique reactivity and further derivation of the 1<i>'</i>-azido <i>C</i>-nucleosides are also reported.
Authors
- Steven De Jonghe (ORCID: https://orcid.org/0000-0002-3872-6558)
- Subhankar Panda (ORCID: https://orcid.org/0000-0003-3077-0690)
- Courtney C. Aldrich (ORCID: https://orcid.org/0000-0001-9261-594X)
- Tej Narayan Poudel (ORCID: https://orcid.org/0000-0002-0390-107X)
- Moyosore O. Orimoloye (ORCID: https://orcid.org/0000-0002-0330-008X)
- Dirk Jochmans (ORCID: https://orcid.org/0000-0002-9265-6028)
- Johan Neyts (ORCID: https://orcid.org/0000-0002-0033-7514)
Institutions
- University of Minnesota (US)
- KU Leuven (BE)
Publication Details
- Journal
- The Journal of Organic Chemistry
- Published
- 2024-11-19
- DOI
- https://doi.org/10.1021/acs.joc.4c01981
- Citations
- 1
- Primary Topic
- Click Chemistry and Applications
- Type
- article
- Field-Weighted Citation Impact
- 0.25
Funders
- National Institute of Allergy and Infectious Diseases