Applications of Piperazine-2,5-diones

The secondary structure of the polypeptide chain in hydrolytic enzymes ensures the spatial proximity of the necessary functional groups, which are responsible for the observed catalytic effect. In synthetic enzyme mimics, it is possible to bring the requisite functionalities into close juxtaposition only if there is a rigid framework to which these groups are attached. It was thus logical to examine cyclic peptides, especially cyclodipeptides, which bear the necessary functional groups for their catalytic activity in ester hydrolysis. 

The efficiency of the catalysis would also depend on the binding of the substrate to the piperazine-2,5-dione by means of weak forces. Imanishi and his group (85BCJ497) have sought to achieve this by means of hydrophobic interactions. They have chosen as substrates p-nitrophenyl esters of long-chain fatty acids the hydrocarbon chain would enter into 

The catalytic effect of these cyclodipeptides on substrates having other charged functionalities, in addition to the p-nitrophenyl ester, has been studied (83MI2). The authors were unable to detect any specific catalysis of the hydrolysis of such substrates. 

Chiral Induction in Piperazine-2,5-dione-Catalyzed Reactions 

Addition of HCN to various aldehydes was carried out by using 2 mol% of the cyclic dipeptide as catalyst and 2 eq of HCN. The reaction was preferably carried out in toluene at -20°C. Under these conditions, benz-aldehyde gave (/ )-mandelonitrile in 97% yield with an enantiomeric excess (ee) of 97%. The use of cyclo[(/ )-Phe-(/ )-His] gave (S)-mandelonitrile with ee of 93%. The presence of electron-withdrawing groups on the phenyl ring of benzaldehyde led to poor ee values. 

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