Biotransformation of hexapropymate in man. Part 2: Isolation and identification of metabolites

This paper deals with the isolation and identification of hexapropymate metabolites in man. This hypnotic drug is hydroxylated on different positions of the cyclohexane nucleus as was shown by IR, 1H-NMR and MS data of the isolated metabolites and their hydrolysis products. For the determination of the position and conformation of the metabolically introduced hydroxyl group, it was necessary to synthesize different reference compounds [12] and compare their physico-chemical data with those of the isolated metabolites. In this way the following phase-I-metabolites could be identified: 4a-hydroxy-1-(2'propynyl)cyclohexanol-1-carbamate (4a-hydroxyhexapropymate), 4e-hydroxy-1-(2'propynyl)cyclohexanol-1-carbamate (4e-hydroxyhexapropymate) and 3e-hydroxy-1-(2'propynyl)cyclohexanol-1-carbamate. The first two metabolites are also partially excreted in the form of glucuronides.