Cyclo-(L-asparagyl-L-asparagyl)[(3S,6S)-3,6-bis(carbamoylmethyl)-piperazine-2,5-dione]: preparation and crystal structure

Abstract

Two methods are described for the preparation of optically pure cyclo-(L-asparagyl-L-asparagyl)[(3S,6S)-bis(carbamoylmethyl)piperazine-2,5-dione]: (i) by self-condensation of (S)-3-aminopyrrolidine-2,5-dione in refluxing acetonitrile, and (ii) by self-condensation of L-asparagine methyl ester at room temperature; the latter method is more efficient. The identity of this previously uncharacterised piperazinedione was confirmed by analytical and spectroscopic data, and by a crystal structure determination, which showed the conformation of the piperazinedione ring to be a bowsprit boat (i.e. quasiequatorial carbamoylmethyl substituents). The angle between the amide units of the piperazinedione ring is 18°. Intramolecular hydrogen bonds are absent from the crystal structure, the packing of which is dominated by intermolecular hydrogen bonds from each piperazinedione CO to the carbamoyl NH₂(each NH of which is engaged in hydrogen bonding to a different molecule of piperazinedione).