Abstract

The ubiquity of piperazine-2,5-dione core (2,5-diketopiperazine, DKP) in biologically active natural products and the preponderance of its heterocyclic framework in many drugs, has encouraged the development of methods for the selective functionalisation of readily available piperazine-2,5-dione precursors. C-functionalisation using DKPs as electrophilic glycine templates is generally mediated by N-acyliminium ions. These intermediates show highly versatile reaction characteristics, which are reflected in an impressive number of synthetic applications. However, even in some very comprehensive reviews dealing with N-acyliminium ions, references to these species derived from piperazine-2,5-diones are scarce. This review is devoted to fill this gap, placing emphasis upon the most suitable precursors of endocyclic and exocyclic acyliminium ions derived from piperazine-diones and their synthetic applications. Other more complex structures that include this framework or a related portion, such as pyrazino[1,2-b]isoquinoline-1,4-diones or the pyrazino[2,1-b]quinazoline-3,6-dione system, are also overviewed.

Keywords: Piperazine-2,5-dione, 2,5-diketopiperazine, DKP, N-acyliminium ions, pyrazino[1,2-b]isoquinoline-1, 4-diones, pyrazino[2,1- b]quinazoline-3, 6-diones, 1,5-imino-3-benzazocins, N-acetylardeemin