The conformation cis of N-acetyl-N-methyl-α,β-dehydroalanine N′-methylamide and saturated analogues

Abstract

A series of three homologous amino acids derivatives: N-acetyl-N-methyl-α,β–dehydroalanine N′-methylamide (1), N-acetyl-N-methyl-L-alanine N′-methylamide (2), and N-acetyl-N-methyl-DL-alanine N′-methylamide have been synthesised. The racemic species undergoes spontaneous separation into L and D-enantiomers. From these two chiral forms, the structure of L-enantiomer (3) was analysed. The molecules of 1 – 3 adopt the cis arrangement of the N-terminal amide bond. The molecular conformations are similar for 1 (φ, ψ = 94.6(1)°, −1.7(1)°) and 3 (φ, ψ = 111.5(1)°, −23.8(1)°), and also 2 (φ, ψ = −114.8(2)°, 29.5(2)°), if inversion through the chiral C2 carbon is considered. They are stabilised by intramolecular N—H…N hydrogen bond. In the case of 1, the π—electron conjugation resulting from the planar arrangement of the C2—C21 double bond and C-terminal amide group is another stabilising force of this conformation. Thus, the N-methyldehydroalanine residue should promotes trans-cis isomerisation to a greater extend than the saturated analogue. The compounds 1 – 3 reveal similar associative pattern and form centrosymmetric dimers linked by the intermolecular N—H…O hydrogen bonds.