A Lactone-Enabled Approach to Metronidazole-Based Scaffolds
A scaffold-divergent approach to metronidazole-based compounds was described. Attempts to prepare N1-hydroxyethyl nitroimidazole-2-carboxylic acid resulted in rapid decarboxylation. A lactone (compound 8) serves as a stable and practical surrogate, enabling access to both oxadiazole and amide derivatives. Density functional theory calculations revealed that the instability of N1-hydroxyethyl nitroimidazole-2-carboxylic acid arises from a low-barrier decarboxylation pathway.
Authors
- Shahriar Mobashery (ORCID: https://orcid.org/0000-0002-7695-7883)
- Xiaotan Yu (ORCID: https://orcid.org/0000-0002-4029-810X)
- Gisela A. González‐Montiel (ORCID: https://orcid.org/0000-0003-0665-5326)
- Mayland Chang (ORCID: https://orcid.org/0000-0002-4333-3775)
- Pradip Shit (ORCID: https://orcid.org/0000-0002-0716-5356)
- Olaf Wiest
Institutions
- University of Notre Dame (US)
Publication Details
- Journal
- The Journal of Organic Chemistry
- Published
- 2026-05-27
- DOI
- https://doi.org/10.1021/acs.joc.6c00559
- Primary Topic
- Chemical Reaction Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institute of General Medical Sciences