Synthesis and NMDA-receptor affinity of 4-oxo-dexoxadrol derivatives

A synthesis of novel dexoxadrol analogues is described, which allows modifications of the piperidine substructure. The key step of the synthesis is a hetero Diels–Alder reaction of the imine 12 with Danishefsky’s diene 6. After separation of the diastereomeric piperidones 14a and 14b, the relative configuration of the unlike configured piperidone 15b was determined by X-ray crystal structure analysis. In receptor binding studies the like configured secondary amine 15a (racemate) showed considerable affinity toward the phencyclidine binding site of the NMDA receptor ( K i = 470 nM).