Poststatin, a new inhibitor of prolyl endopeptidase .3. Optical resolution of 3-amino-2-hydroxyvaleric acid and absolute configuration of poststatin

3-Amino-2-hydroxyvaleric acid was prepared, and separated into its diastereomers. The relative stereochemistry was determined by H-1 NMR in their oxazolidone derivatives. The threo-isomer was resolved by (S)-1-(1-naphthyl)ethylamine in the N-(p-methoxybenzyloxycarbonyl) derivative. The absolute configuration of (-)-threo-3-(p-methoxybenzyloxycarbonyl)amino-2-hydroxyvaleric acid was confirmed to be 2R,3S. The absolute configuration of 3-amino-2-oxovaleric acid in poststatin was confirmed to be S by comparison of the four stereoisomers of methyl N,O-bis(3,5-dinitrobenzoyl)-3-amino-2-hydroxyvalerate derived from 3-amino-2-hydroxyvaleric acid and that derived from 3-amino-2-oxovaleryl moiety of poststatin by means of HPLC with chiral column.