title: Investigation of conjugate addition/intramolecular nitrone dipolar cycloadditions and their use in the synthesis of dendrobatid alkaloid precursors.
abstract: The sequential intramolecular conjugate addition of the oxime 13 followed by intramolecular dipolar cycloaddition of the intermediate nitrone 14 affords a mixture of the isoxazolidines 15, 16 and 17. The tricyclic 6,5,5-adduct 15 is believed to be the product of kinetic control and can be equilibrated with the epimeric tricyclic 6,5,5-isoxazolidine 17 through a beta-elimination/conjugate addition process. Conditions have been developed for the two-step conversion of the ketone 12 under thermodynamic control into the racemic tricyclic 6,6,5-adduct 16 which is the core precursor of all the known histrionicotoxin alkaloids.
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UK CB2 1EW.
authors.forename: Helen T
authors.initials: HT
authors.lastname: Horsley
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Holmes
authors.forename: John E
authors.initials: JE
authors.lastname: Davies
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Goodman
authors.forename: María A
authors.initials: MA
authors.lastname: Silva
authors.forename: Sofia I
authors.initials: SI
authors.lastname: Pascu
authors.forename: Ian
authors.initials: I
authors.lastname: Collins
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003500:Cyclization; D007212:Indolizines / Q000737:chemistry; D007555:Isoxazoles / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry; D007700:Kinetics; D009589:Nitrogen Oxides / Q000737:chemistry*; D010091:Oximes / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D000470:Alkaloids; D007212:Indolizines; D007555:Isoxazoles; D007659:Ketones; D009589:Nitrogen Oxides; D010091:Oximes; C015388:nitrones