SYNTHESIS OF DEUTERIO-L-AMPHETAMINE D1 SULFATE

In order to investigate the isotope effect on the enzymatic deamination of amphetamine, deuterio‐l‐amphetamine, d1 sulfate was synthesized by the selective reduction of phenyl‐2‐propanone oxime with lithium aluminum deuteride, followed by resolution of the racemic product. The yield of racemic amphetamine was 46% when approximately equimolar quantities of the oxime and LiAlD4 were employed. The identity of the deuterated amphetamine base was confirmed by determination of the physical properties of the racemic mixture. From NMR data, deuterium was found exclusively in the methine hydrogen position at a purity of greater than 99 atom percent. The optical isomers of deuterio‐amphetamine were resolved through repeated fractional crystallization of the d‐amphetamine‐d‐bitartrate and l‐amphetamine‐l‐bitartrate diastereomers. The isomers were found to possess 97 to 99% optical purity, based on values for pure isomers of protio‐amphetamine. In vitro metabolism studies indicate that a significant deuterium isotope effect operates in the oxidative deamination of deuterio‐l‐amphetamine. Under specified conditions, the ratios of apparent rate constants (kH/kD) based on initial velocities, yield a value of 2.0 ± 0.3. Copyright © 1969 Wiley‐Liss, Inc., A Wiley Company