Design and synthesis of propeller-shaped dispiroisoxazolinopiperidinochromanones

Richard D. Carpenter, Patrick B. DeBerdt, Jason B. Holden, Kristin A. Milinkevich, Taewoo Min, Dan Willenbring, James C. Fettinger, Dean J. Tantillo, Mark J. Kurth

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)225-229
Number of pages5
JournalJournal of Combinatorial Chemistry
Volume10
Issue number2
DOIs
StatePublished - Mar 2008

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Computational chemistry
Information Centers
Regioselectivity
Nitriles
Oximes
Cycloaddition
Bioassay
Cycloaddition Reaction
National Institutes of Health (U.S.)
Propellers
Biotechnology
Carboxylic Acids
Biological Assay
Oxides
Biological Availability
Libraries
X-Rays
Health
Databases
Synthesis

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Discrete Mathematics and Combinatorics

Cite this

Carpenter, R. D., DeBerdt, P. B., Holden, J. B., Milinkevich, K. A., Min, T., Willenbring, D., ... Kurth, M. J. (2008). Design and synthesis of propeller-shaped dispiroisoxazolinopiperidinochromanones. Journal of Combinatorial Chemistry, 10(2), 225-229. https://doi.org/10.1021/cc700173x

Design and synthesis of propeller-shaped dispiroisoxazolinopiperidinochromanones. / Carpenter, Richard D.; DeBerdt, Patrick B.; Holden, Jason B.; Milinkevich, Kristin A.; Min, Taewoo; Willenbring, Dan; Fettinger, James C.; Tantillo, Dean J.; Kurth, Mark J.

In: Journal of Combinatorial Chemistry, Vol. 10, No. 2, 03.2008, p. 225-229.

Research output: Contribution to journalArticle

Carpenter, RD, DeBerdt, PB, Holden, JB, Milinkevich, KA, Min, T, Willenbring, D, Fettinger, JC, Tantillo, DJ & Kurth, MJ 2008, 'Design and synthesis of propeller-shaped dispiroisoxazolinopiperidinochromanones', Journal of Combinatorial Chemistry, vol. 10, no. 2, pp. 225-229. https://doi.org/10.1021/cc700173x
Carpenter RD, DeBerdt PB, Holden JB, Milinkevich KA, Min T, Willenbring D et al. Design and synthesis of propeller-shaped dispiroisoxazolinopiperidinochromanones. Journal of Combinatorial Chemistry. 2008 Mar;10(2):225-229. https://doi.org/10.1021/cc700173x
Carpenter, Richard D. ; DeBerdt, Patrick B. ; Holden, Jason B. ; Milinkevich, Kristin A. ; Min, Taewoo ; Willenbring, Dan ; Fettinger, James C. ; Tantillo, Dean J. ; Kurth, Mark J. / Design and synthesis of propeller-shaped dispiroisoxazolinopiperidinochromanones. In: Journal of Combinatorial Chemistry. 2008 ; Vol. 10, No. 2. pp. 225-229.
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