Diketopiperazine

A diketopiperazine (DKP), also known as a dioxopiperazine or piperazinedione, is a class of organic molecules in which the two nitrogen atoms of a piperazine 6-membered ring are part of amide linkages. There are three regioisomers possible, differing in the locations of the two carbonyl groups around the ring. While these isomers share a piperazine core, optimal strategies for their synthesis differ.^[1] The 2,3-diketopiperazines may be viewed as oxamides obtained from ethylenediamine. 2,5-Diketopiperazines are cyclodipeptides obtained via condensation of two α-amino acids. 2,6-Diketopiperazines may be viewed as cyclized imide derivatives derived from iminodiacetic acids.

DPKs can be visualized as α-amino amides where the nitrogen atoms are constrained into a six membered ring:

The diketopiperazines:2,3-, 2,5, and 2,6-isomers.

As a result of the structural similarities of DKPs to peptides,.^[2] their appearance in biologically active natural products has inspired medicinal chemists to use DKPs to circumvent the poor physical and metabolic properties of peptides in the course of drug discovery.

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