Synthesis of (S)- and (R)-5-oxo-piperazine-2-carboxylic acid and its application to peptidomimetics.

A straightforward synthesis of (S)- and (R)-N-Boc-5-oxo-piperazine-2-carboxylic acid is reported starting from l- or d-serine and ethyl glyoxylate. Those were evaluated as constituents in two tetrapeptides by studying their secondary structure by 1H NMR spectroscopy. In the case of Boc-Val-(S)-PCA-Gly-Leu-OMe, two readily interconverting conformations (in a 40%:60% ratio) were observed, differing for the cis−trans isomerizaton of the tertiary amide bond, while Boc-Val-(R)-PCA-Gly-Leu-OMe displayed an equilibrium between a γ-turn and a type II β-turn conformation.