Piperazinediones oxidation

An extremely interesting and novel method has been described (91TL133). The principle involved is the intramolecular Diels-Alder addition of a 2,4-dienoic acid amide with an azodicarbonyl moiety. /V-Sorbyl-proline (27) was condensed with an acylhydrazine to form (28). Oxidation of this with lead tetraacetate (LTA) in boiling benzene resulted in the piperazinedione (30). This must have come about via (29), which could undergo an intramolecular Diels-Alder reaction. The structure and stereochemistry of (30) were confirmed by X-ray crystallography. The two new chiral centers have the R configuration as shown in (Scheme 9). 

Oxidative cyclizations of cyclodipeptides incorporating tryptophan have also been reported (81TL5323). Thus, irradiation of the piperazinedione (39) in formic acid in the presence of a sensitizer such as proflavine or chloranil gave the hydroxypyrroloindole (40). Oxidation with thallium (III) trifluoroacetate gave the dimer (41) in 3% yield. 

Other Reactions The alkylthio group attached to the 3 (or 6) position of the piperazinedione can be eliminated or oxidized to the sulfone (73CB165), or displaced by a peroxide group. Some of the transformations are shown in Scheme 47. 

A number of structurally interesting natural alkaloids have been isolated from various fungi that contain the unique bicycio [2.2.2] ring system constituted mainly from tryptophan, proline, and substituted proline derivatives where the olefinic unit of the isoprene moiety has been formally oxidatively cycUzed across the a-carbon atoms of a cycUc dipeptide (a piperazinedione or diketopi-... 

B. Direct Oxidation of Amino Acid Derivatives and Piperazinediones.285... 

K) A final route which cannot a priori be excluded as a possible biosynthetic pathway is the direct a-oxidation of amino acid derivatives to a-hydroxy-a-amino acid derivatives followed by elimination of water. In vitro oxidation of piperazinediones to a-hydroperoxides occurs very readily (cf. Section V.). The isolation of numerous dehydropiperazine-diones and corresponding mercaptopiperazinediones containing proline (or benzoproline , i. e. dihydroindole) units 341) necessitates the consideration of this route as a possible biosynthetic pathway. The hydroperoxypiperazinediones can readily be converted into dehydro-and mercaptopiperazinediones. 

P. G. Sammes has dehydrogenated the iminoethers of piperazine-diones with 2,3-dichloro-5,6-dicyanobenzoquinone 243). Cyclo-L-Pro-L-Pro can be oxidized with this reagent directly to pyrocoll 243). The use of sulfur as oxidizing agent has been successful only with N-acetylated piperazinediones 242). 

With regard to the biosynthesis of the epidithiopiperazinediones, U. Schmidt and J. Hausler studied the photochemical oxidation of piperazinediones in some detail (168, 349), a reaction which takes place with exceptional ease in many cases. Piperazinediones which are not kept sealed in an oxygen-free atmosphere contain, if exposed to light, considerable amounts of hydroperoxides within a few weeks. Photochemical oxidation of piperazinediones in the presence of catalytic quantities of benzophenone yields mono- and bis-hydroperoxides in which the configuration of the original compounds is largely retained. As an example, the main product of photochemical oxidation of L-prolyl-L-proline... 

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