Victorins, a family of peptide toxins, produced by the fungal pathogen Cochliobolus victoriae and responsible for disease of some oat varieties, contain a β-chlorodehydroalanine residue, ΔAla(βCl). To determine the conformational properties of this unique dehydroamino acid, a series of model compounds was studied using X-ray, NMR, and FT-IR methods, supported by theoretical calculations. The ΔAla(βCl) geometrical isomers differ in conformational profile. The isomer Z prefers the helical conformation α (φ, ψ = -61°, -24°), PPII type conformation β (φ, ψ = -47°, 136°), and semiextended conformation β2 (φ, ψ = -116°, 9°) in weakly and more polar solutions. The isomer E prefers mainly the extended conformation C5 (φ, ψ = -177°, 160°), but with an increase of the environment polarity also conformations β (φ, ψ = -44°, 132°) and α (φ, ψ = -53°, -39°). In the most stable conformations the N-H···Cl hydrogen bond (5γ) occurs, created between the chlorine atom of the side chain and the N-H donor of the flanking amide group. The method of synthesis of the β-chlorodehydroalanine residue is proposed, by chlorination of dehydroalanine and then the photoisomerization from the isomer Z to E. The presented results indicate that the assignment of the geometrical isomer of the ΔAla(βCl) residue in naturally occurring victorins still remains an open question, despite being crucial for biological activity.
Keywords: N−H···Cl hydrogen bond; Ramachandran diagrams; amino acid synthesis; conformational analysis; dehydroamino acids; photoisomerization.