A short route to enantiomerically pure benzophenanthridinone skeleton: synthesis of lactone analogues of narciclasine and lycoricidine.
Condensation of functionalized o-toluamide anions on a carbohydrate-derived lactone, followed by intramolecular aldol cyclization, provides enantiomerically pure 2-arylcyclohexenones. Different approaches for the stereoselective transformation of the carbonyl group of these key intermediates into an amino group were unsuccessful. However 1,4-addition of thiolate and concomitant ring closure to isocoumarine provided a useful method for the transformation of the tertiary amide function. Opening of the isocoumarin with ammonia provided the corresponding amide and recovery of the enone system. Subsequent reductive amination of this cyclohexenone was found to depend on the nature of the protecting groups and led to the protected form of 4-epi- and -iso-narciclasine. Oxo analogues of narciclasine and epi-narciclasine and lycoricidine were also obtained after reduction of the enone and subsequent lactonization. They showed no biological activity as antitumor agents.
Ibn-Ahmed
Said
S
Groupe SUCRES, UMR 7565 CNRS-Université Henri Poincaré Nancy 1, BP 239, F-54506 Nancy-Vandoeuvre, France.
Khaldi
Mustapha
M
Chrétien
Françoise
F
Chapleur
Yves
Y
D047151:Amaryllidaceae Alkaloids / Q000138:chemical synthesis*; D000970:Antineoplastic Agents / Q000138:chemical synthesis; D008956:Models, Chemical; D015394:Molecular Structure; D010617:Phenanthridines / Q000138:chemical synthesis*; D013237:Stereoisomerism
D047151:Amaryllidaceae Alkaloids; D000970:Antineoplastic Agents; D010617:Phenanthridines; C500283:lycoricidine; C010753:narciclasine