CIS-TRANS ISOMERISM OF THE AMIDE BOND IN ETO-AC-L-ALA-L-GLU

Evidence for the existence of cis-trans isomerism of Ac-Ala amide bond in EtO-Ac-L-Ala-L-Glu (1) is given by the NMR study of 1, EtO-Ac-Gly-L-Glu (2), and EtO-Ac-L-Ala-D-Glu (3). Energy profiles for the rotation about the Ac-Ala amide bond of 1, 2 and 3 were calculated by molecular mechanics using DISCOVER program and by semi-empirical molecular orbital method AM1. Molecular mechanics indicates that the cis and trans isomers of 1 have about the same energy. In contrast the trans isomers of 2 and 3 are energetically favoured. The semi-empirical AM1 method predicts the cis isomer of 1 and 2 to be more stable. For 3 cis and trans isomers of comparable energy resulted. The results are discussed and compared to experimental data.