Synthesis of Four Diastereoisomers of Histopine

Four isomers of histopine, N2-(1-carboxyethyl)histidine, were prepared to provide their physicochemical properties. A diastereomeric mixture, (RS),(S)-histopine (N2-[(RS)-1-carboxyethyl]-(S)-histidine), was synthesized from 2-oxopropionic acid and (S)-histidine by reduction with sodium cyanoborohydride. The mixture was separated into its components, (S),(S)-histopine and (R),(S)-histopine, by an ion-exchange column chromatography. In a similar manner (R),(R)-histopine and (S),(R)-histopine were prepared. Configurations of the four isomers obtained were assumed from their ORD data by comparison with those of the isomers of octopine (N2-(1-carboxyethyl)arginine) with a definite configuration.