A library of novel, propeller-shaped dispirotriheterocyclic isoxazolinopiperidinochromanones is reported. Each rigid dispirotriheterocycle was prepared in five linear steps from commercially available tert-butyl 4-oxopiperidine-l-carboxylate and various derivatives of l-(2-hydroxyphenyl) ethanone, benzaldehyde oxime, and carboxylic acids. Computational chemistry was employed to analyze the three-dimensional geometries of these dispirotriheterocycles, as well as to generate chemoinformatic bioavailability data. X-ray crystallographic structure determination verified the regioselectivity of the nitrile oxide 1,3-dipolar cycloaddition reaction. The resulting library of compounds has been added to the National Institutes of Health repository (∼10 mg of each with ≥90% purity) for pilot-scale biomedical studies with bioassay data available at the National Center for Biotechnology Information PubChem database.
ASJC Scopus subject areas
- Drug Discovery
- Organic Chemistry
- Discrete Mathematics and Combinatorics