Synthesis of chiral non-racemic 3-(dioxopiperazin-2-yl)propionic acid derivatives

Starting with the proteinogenic amino acid (S)-glutamate () a facile, high yielding synthesis of the chiral non-racemic 3-(dioxopiperazin-2-yl)propionates , , and is presented. Key intermediates in the synthesis of N1-benzyl substituted (dioxopiperazin-2-yl)propionates and are the N-monobenzylglutamate and the chloroacetamide , which allow introduction of various substituents in position 4 of the piperazine ring. In receptor binding studies with radioligands the 3-(piperazin-2-yl)propanol was found to have promising affinity for σ1-receptors (Ki=66.1 nM).