Unsaturated Piperazinediones

Shin, C., M. Hayakawa, T. Suzuki, A. Ohtsuka, and J. Yoshimura a,p-Unsatur-ated Carboxylic Acid Derivatives. XIII. The Synthesis and Configuration of Alkyl 2-Acylamino-2-alkenoates and Their cyclized 2,5-Piperazinedione Derivatives. Bull. Chem. Soc. Japan 51, 550 (1978). 

The available data on piperazinediones have been the subject of a recent detailed survey by P. G. Sammes (341). Since then only few additional reports on naturally occurring unsaturated cyclodipeptides (91, 188, 189, 204, 248, 249), 3-hydroxy substituted cyclodipeptides (2) (124, 440) and epidithiocyclopeptides (27, 36, 135, 260, 399) have been published. 

Epidithiopiperazinediones (3) are cyclodipeptides of a-mercapto-a-amino acids in the form of their disulfides. All compounds of this structural type possess high cell toxicity and have antiviral properties by virtue of their inhibition of RNA synthesis. The isolation, together with the epidithiopiperazinediones, of the analogous unsaturated piperazinediones is a significant finding with a bearing on biosynthetic pathways. 

Piperazinedione condenses easily with benzaldehyde in the presence of acetic anhydride/sodium acetate to yield 3,6-dibenzylidene-2,5-piperazinedione (343, 344). Analogous preparations have been conducted with heterocyclic and unsaturated aliphatic aldehydes (19), but not with saturated aliphatic aldehydes. The synthesis of alkylidenepiperazine-diones can be realized by condensation of N,N -diacetylpiperazine-diones with aliphatic aldehydes in the presence of potassium t-butoxide (138, 140), conditions also applicable to the synthesis of monoarylidene-piperazinediones. A second condensation is however only possible with aromatic aldehydes. 

Table 2. Examples of Piperazinediones Yielding Unsaturated Derivatives by Elimination...

S2CI2 has been used to form a disulfide bridge by reaction with alkali 2,5-dioxopiperazine-3,6-dicarboxylates and by addition reaction to unsaturated piperazinediones respectively 345, 104). 

To the more inert double bond of unsaturated piperazinediones methane sulfenyl chloride or sulfur chloride was added, the p-thio compounds being formed in every case 444). 

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