SYNTHESIS OF EACH STEREOISOMER OF [3-H-2(1)]PHENYLALANINE AND EVALUATION OF THE STEREOCHEMICAL COURSE OF THE REACTION OF (R)-PHENYLALANINE WITH (S)-PHENYLALANINE AMMONIA-LYASE

The four stereoisomers of [3-H-2(1)] phenylalanine have been prepared. each as a single enantiomer in ca. 98% diastereoisomeric excess and with ca. 99% deuterium incorporation, by Side-chain bromination of phenylalanine derivatives, followed by deuteriolysis of each of the diastereoisomeric product bromides with deuterium over 5% palladium-on-carbon. The latter reactions, proceeded with retention of : configuration. (2R,3S)-[3-H-2(1)] Phenylalanine reacted with (S)-phenylalanine ammonia-lyase to give [3-H-2(1)] -trans-cinnamic acid, with 92% deuterium incorporation; while the (2R,3R) -stereoisomer of the deuteriated phenylalanine gave [3-H-2(1)] -trans-cinnamic acid with 27% deuterium incorporation. These results indicate that reaction of (R)-phenylalanine with the enzyme involves mainly loss of the 3-pro-R hydrogen and ammonia, in an antiperiplanar elimination process analogous to that previously reported for (S)-phenylalanine,while a minor pathway for reaction of :(R)-phenylalanine is either isomerization to (S)-phenylalanine; before elimination, or synperiplanar elimination.