Stereochemical Studies on Medicinal Agents. IV.¹ Conformational Analysis of Ephedrine Isomers and Related Compounds

The conformational preference of ephedrine isomers has been deduced from nmr studies of these compounds and the corresponding 3-methyl-2-phenylmorpholine diastereomers. The nmr data suggest that, in a variety of solvents, the ephedrines are intramolecularly hydrogen bonded both as the free bases and salts. A possible explanation for the stereo structure-activity relationship of the ephedrines has been advanced. Arylethanol-amines such as epinephrine and other related physiologically active compounds have been suggested to exist primarily as internally hydrogen-bonded species.