Insight into the Structure of Antifungal Cyrmenins: Conformational Studies of Unique Dehydroamino Acid, O-Methyldehydroserine.

Abstract

O-Methyldehydroserine, ΔSer(Me), is a non-standard α,β-dehydroamino acid, which occurs naturally in Cyrmenins with potential pharmaceutical application. The C-terminal part and the side chain of the ΔSer(Me) residue constitute the β-methoxyacrylate unit, responsible for antifungal activity of Cyrmenins. The short model, Ac-ΔSer(Me)-OMe, was analyzed considering the geometrical isomer Z (1) and E (2). The Ramachandran diagrams were created for both isomers, using quantum chemical calculations, to show possible conformations for isolated molecules (in vacuo), in weakly polar (chloroform) and polar (water) environments. The Ac-(Z)-ΔSer(Me)-OMe (1) was synthesized and the single-crystal X-ray diffraction analysis together with FT-IR spectra were performed. The detailed analysis of the conformations of the (Z)-ΔSer(Me) residue is presented considering the intra- and intermolecular interactions as well as their influence on the β-methoxyacrylate part. It is concluded that the β-methoxyacrylate structural motif is able to maintain a planar geometry, crucial for biological activity, regardless of the conformation adopted by O-methyldehydroserine.