Mastering chiral substituted 2-oxopiperazines

The piperazine moiety is an important pharmacophore which is found in a large number of biologically active molecules. Although the syntheses of piperazine derivatives have been known for almost a century, chiral syntheses of 2-oxopiperazines have been rarely reported and still remain a daunting challenge to organic chemists. Therefore, the search of efficient routes towards these compounds with substitution at different ring positions are of crucial and particular significance in view of the profound importance of substituted piperazine ring systems in medicinal chemistry and drug discovery. This review provides a comprehensive survey of the methods available for the preparation of chiral 2-oxopiperazines.