Investigation of conjugate addition/intramolecular nitrone dipolar cycloadditions and their use in the synthesis of dendrobatid alkaloid precursors.
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.
Horsley
Helen T
HT
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UK CB2 1EW.
Holmes
Andrew B
AB
Davies
John E
JE
Goodman
Jonathan M
JM
Silva
María A
MA
Pascu
Sofia I
SI
Collins
Ian
I
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
D000470:Alkaloids; D007212:Indolizines; D007555:Isoxazoles; D007659:Ketones; D009589:Nitrogen Oxides; D010091:Oximes; C015388:nitrones