Racemic and optically active trans 2,6-dimethyl analogues of the reversed ester of pethidine

The preparation and stereochemical characterization of (+/-)-1,trans 2,6-trimethyl-4-phenyl-4-propionoxypiperidine hydrochloride and its (+)- and (-)-antipodes are described. The absolute configurations of the antipodes were established by X-ray analysis of the corresponding (-)-4-piperidinol hydrobromide. In antinociceptive tests on mice and rats, the (+)-2S,6S ester proved the more potent antipode by factors of at least 10 (rats) and 20 (mice), a result consistent with earlier proposals made about the probable uptake conformation of pethidine reversed esters at opioid receptors.