Synthesis of individual glutamate-containing phosphonamidothionate stereoisomers

The acquisition of the individual stereoisomers of chiral phosphonothioic acids is anticipated to reveal the significance of phosphorus stereochemistry upon the inhibition of metallocarboxypeptidases as well as their utility as chiral and stereoselective inhibitory probes. Two methods for preparing individual glutamate-containing phosphonamidothioic acid diastereomers have been identified. One method achieves the resolution through fractional crystallization of the intermediate 9-fluorenemethoxy phosphonamidates while the second does so through chromatographic resolution of intermediate β-(acylmercapto)ethyl phosphonamidothiolates.