Stereoselective syntheses and CNS activity of novel tricyclic amines.
The enantiomerically pure amines (+)-5, (-)-9, (+)-11 and (+)-12 are stereoselectively prepared by reductive amination of the ketone (-)-4 [-->(+)-5], LiAlH4 reduction of the oxime (-)-7 followed by reductive methylation [-->(-)-9], SN2-substitution of the benzenesulfonate 10 [-->(+)-11] and reductive methylation of (+)-11 [-->(+)-12]. In the same way the racemic amines (+/-)-5, (+/-)-9, (+/-)-11 and (+/-)-12 are accessible starting from the racemic ketone (+/-)-4. Kinetic resolution of the racemic ketone (+/-)-4 with baker's yeast leads to the dextrorotatory ketone (+)-4 (86% ec), which is transformed via the methanesulfonate 16 into the tricyclic amines (-)-11 and (+)-17. Weak sedative effects are observed after application of the amines (+)-5, (+/-)-5, 0-9, (+/-)-9(+)-12, and (+/-)-12 to mice. Strong sedation is caused by (+/-)-11 with the dextrorotatory enantiomer (+/-)-11 being more effective than the levorotatory enantiomer (-)-11.
Wünsch
B
B
Institut für Pharmazie und Lebensmittelchemie, Ludwig-Maximilians-Universität München, Germany.
Diekmann
H
H
Höfner
G
G
D000588:Amines / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D002491:Central Nervous System Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000138:chemical synthesis / Q000494:pharmacology; D051379:Mice; D013237:Stereoisomerism
D000588:Amines; D002491:Central Nervous System Agents; D006993:Hypnotics and Sedatives