A cyclic carbo-isosteric penta-depsipeptide: cyclo(Phe(1)-d-Ala(2)-Gly(3)-Phe(4)-APO(5)).

Abstract

The title compound, cyclo(Phe(1)-d-Ala(2)-Gly(3)-Phe(4)-APO(5)), C26H32N4O5, is the minor diastereoisomer of a cyclic penta-peptidomimetic analogue containing a novel 2-amino-propyl lactone (APO) motif, which displays the same number of atoms as the native amino acid glycine and has a methyl group in place of the carbonyl O atom. The crystal structure presented here allows the analysis of the secondary structure of this unprecedented cyclic carbo-isosteric depsipeptide. The conformation of the central ring is stabilized by an intra-molecular N-H⋯O hydrogen bond between the carbonyl O atom of the first residue (Phe(1)) and the amide group H atom of the fourth residue (Phe(4)). Based on the previously reported hydrogen bond and on the values of the torsion angles ϕ and ψ, the loop formed by the first, second, third and fourth residues (Phe(1), d-Ala(2), Gly(3) and Phe(4)) can be classified as a type II' β-turn. The loop around the new peptidomimetic motif, on the other hand, resembles an open γ-turn containing a weak N-H⋯O hydrogen bond between the carbonyl group O atom of the fourth residue (Phe(4)) and the amide unit H atom of the first residue (Phe(1)). In the crystal, the peptidomimetic mol-ecules are arranged in chains along the b-axis direction. Within such a chain, the mol-ecules of the structure are linked via N-H⋯O hydrogen bonds between the amide group H atom of the secondary residue (d-Ala(2)) and the carb-oxy unit O atom of the fourth residue (Phe(4)) in a neighboring mol-ecule. The newly formed methyl stereocentre of the APO peptidomimetic motif (APO(5)) was obtained as the minor diastereoisomer in a ring-closing reductive amination reaction and adopts an R configuration.