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Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
Published on: February 7, 2019
A Lactone-Enabled Approach to Metronidazole-Based Scaffolds
Xiaotan Yu1, Gisela A González-Montiel1, Pradip Shit1
1Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States.
None:
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.
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