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Updated: Sep 14, 2026

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
Stereoselective syntheses and CNS activity of novel tricyclic amines
B Wünsch1, H Diekmann, G Höfner
1Institut für Pharmazie und Lebensmittelchemie, Ludwig-Maximilians-Universität München, Germany.
Abstract:
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.
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