BRIDGEHEAD NITROGEN COMPOUNDS AS POTENTIAL ANALGETICS

Some bridgehead nitrogen analogs of pethidine (Ia) and its reversed ester (Ib) were synthesized in order to obtain data on the importance of N-dealkylation and stereochemistry in the production of analgesia. The isomeric 7-acetoxy-7-phenylindolizidines (VIIa, VIIb) were prepared from the corresponding indolizidinol (VIa, VIb) and 2-acetoxy-2-phenylquinolizidine (XVb) from the quinolizidinol XlVb. Ethyl 2-phenylquinolizidine-2-carboxylate (XXIII) was synthesized from XVIII via XIX-XXIII; one isomer was isolated. Moderate to weak analgetic activity was shown by most compounds, the ester XXIII being the most potent, having about half the activity of pethidine. © 1969, American Chemical Society. All rights reserved.