Stereochemical Studies on Medicinal Agents. 15. Absolute Configurations and Analgetic Potencies of Enantiomeric Diastereomers of 3-Allyl-1-methyl-4-phenyl-4-propionoxypipendine

Enantiomeric diastereomers of the title compound la, b were prepared and their absolute configurations determined by chemically relating them to (3R,4S)- and (3S,4R)-1,3-dimethyl-4-phenylpiperidin-4-ol. The analgetic potency of (3R,4S)-la (8a) is 40 times that of morphine and 260 times that of its enanti-omer 10a. Enantiomers of lb (8b and 10b) exhibited no stereoselectivity and possessed a relatively low order of potency (~ 1/12 that of morphine). The fact that this is in marked contrast to the reported high antipodal stereoselectivity for β-prodine suggests that the mode of interaction of lb with analgetic receptors differs from that of β-prodine. Possible reasons for the change of stereoselectivity are discussed.