[Synthesis of enantiomerically pure 6,10-epoxybenzocycloocten-7-amines with CNS activity].
In an oxa-Pictet-Spengler reaction the methyl (S)-phenyllactate 6 and methyl levulinate (7a) are condensed to the 2-benzopyrans cis-8a and trans-8a, which react with CH3I to yield the dimethyl ethers cis-9a and trans-9a. Cis-9a and trans-9a can be separated by medium pressure liquid chromatography. In the subsequent Dieckmann-Cyclisation cis-9a is transformed to the laevorotatory beta-ketoester (-)-10a, while the dextrorotatory enantiomer (+)-10a is obtained from trans-9a after C-3-epimerisation. With Eu(hfc)3 the ketone (-)-11, prepared by saponification and decarboxylation of (-)-10a, proves to be enantiomerically pure. By reductive amination, ketone (-)-11 is transformed to the amines (-)-12a and (-)-12b. Symptoms typical for central damping are caused after i.p. application of (-)-12a and (-)-12b to mice. In the mouse writhing-test (-)-12a HCl affords an ED50-value of 7.0 mg/kg, comparable with the ED50-value of tramadol.
Wünsch
B
B
Institut für Pharmazie und Lebensmittelchemie, Universität München.
Zott
M
M
Höfner
G
G
D000818:Animals; D002490:Central Nervous System / Q000187:drug effects*; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D011083:Polycyclic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D011083:Polycyclic Compounds; D009270:Naloxone
Synthese enantiomerenreiner 6,10-Epoxybenzocycloocten-7-amine mit ZNS-Aktivität.