Unusual mechanism for an aminomutase rearrangement: retention of configuration at the migration termini.

The phenylalanine aminomutase from Taxus catalyzes the vicinal exchange of the amino group and the pro-3S hydrogen of (2S)-α-phenylalanine to make (3R)-β-phenylalanine. While the migration of the amino group from C2 of the substrate to C3 of the product is already known to proceed intramolecularly with retention of configuration, the stereochemistry of the hydrogen transfer remained unknown, until now. The chemical shifts of the prochiral hydrogens of authentic (3R)-β-phenylalanine were established by 1H NMR, and the configuration of each hydrogen was assigned by 2H NMR analysis of a racemic mixture of [2,3-2H2]-(2S,3R)- and (2R,3S)-β-phenylalanines synthesized via syn addition of deuterium gas with palladium catalyst to stereospecifically reduce the double bond of an N-acetyl enamine. After the aminomutase was incubated with [3,3-2H2]-(2S)-α-phenylalanine, the derived deuterium-labeled β-diastereoisomer product, derivatized as the N-acetyl methyl ester, was analyzed by 2H NMR, which revealed that the mut...