Design and synthesis of propeller-shaped dispiroisoxazolinopiperidinochromanones.
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-1-carboxylate and various derivatives of 1-(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 (approximately 10 mg of each with > or =90% purity) for pilot-scale biomedical studies with bioassay data available at the National Center for Biotechnology Information PubChem database.
Carpenter
Richard D
RD
Department of Chemistry, University of California, One Shields Avenue, Davis, California 95616, USA.
DeBerdt
Patrick B
PB
Holden
Jason B
JB
Milinkevich
Kristin A
KA
Min
Taewoo
T
Willenbring
Dan
D
Fettinger
James C
JC
Tantillo
Dean J
DJ
Kurth
Mark J
MJ
D018360:Crystallography, X-Ray; D015195:Drug Design; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry*
D010880:Piperidines