Dioxopiperazines unsaturated

Sammes and cowoikers devised a promising solution to the synthesis of substituted P-silyl sulfones, which has been exploited in a new approach to the antibiotic bicyclomycin (Scheme 44). In their approach the P-silyl sulfone (125) was prepared by conjugate addition of the lithium enolate of the mono-imino ether derivative (123) of a dioxopiperazine to the unsaturated P-silyl sulfone (124). After oxidative cyclization to the bicyclic system (126), the latent alkene functionality was unleashed in 89% yield on treatment with TBAF in THF at room temperature to give the basic skeleton of bicyclomycin. 

Further, hydantoin,967 thiohydantoin, dioxopiperazine, and rhodanine have all been used in similar condensation, yielding the derived <%,/ -unsaturated compounds. 

Cyclization of esters of type (304) is sometimes accompanied by elimination and leads to cyclic derivatives of dehydro-N-hydroxyamino acids, as happens in the case (304) itself which results in formation of l,4-dihydroxy-3,6-diisobutylidene-2,5-dioxopiperazine (305) (140) (Scheme 59). Shin and coworkers (207) obtained unsaturated N-hy-droxydiketopiperazines (307) from a,p-dehydro-halogenoacylamino acids (306) by cycUzation with hydroxylamine in ethanol in the presence of sodium alcoholate (Scheme 60). 

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). 

The double bond in unsaturated dioxopiperazines is more inert than that of acylenamino acids towards addends. The acid catalysed addition of mercaptans and thiolacetic acid to various dehydrodioxopiperazines has been described by Machin and Sammes 242). The kinetically controlled reaction leads to the formation of the a-product, admittedly in very moderate yield in the case of addition of thiolacetic acid. 

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