Bis-lactim ethers of cyclic dipeptides. 1. Compounds derived from cyclo(Gly-L-Val)

We determined the crystal structures of four bis-lactim ethers which carry an isopropyl group and a second substituent opposite to it: (2R,5S)-2-[(1R) -1-naphth-1-yl-2-nitroethyl]-5-isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, C21H25N3O4, (I), (2R,5S)-2-[(1R)-1-(3,4-dimethoxyphenyl)-2-nitroethyl]-5-i sopropl-3,6-dimethoxy-2,5-dihydropyrazine, C19H27N3O6, (II), (IR,2S,3R)-1-[ (2R,5S)-5-isopropyl-3,6-dimethoxy-2,5 pyrazin-2-yl]-2-methyl-2,3-epoxybutan -1-ol, C14H24N2O4, (III), and (S)-alpha-[(2R,5S)-5-isopropyl-3,6-dimethoxy- 2,5- dihydropyrazin-2-yl]benzyl alcohol, C16H22N2O3, (IV) Crystal structure s of this type of dihydropyrazine have been published in a chemical but not in a structural context. Therefore, we present an overview of all known st ructures of this kind. The geometrical parameters of the dihydropyrazine ri ng are summarized and the preferred conformations of the substituents are a nalyzed. The characteristic features of the bis-lactim ethers are compared with those of dihydrooxazinones, a similar type of heterocycle containing o ne lactim ether moiety. Although the folded conformation, in which an aroma tic ring shields the heterocycle, should in principle be possible for three of the four structures, it is not observed at ail. However, the explanatio n given for the dihydrooxazinones can also be applied to bis-lactim ethers and shows that the preferred orientation of the tertiary C-H bonds determin es the conformation of the substituents.