title: Conformational preferences and synthesis of isomers Z and E of oxazole-dehydrophenylalanine.
abstract: Dehydrophenylalanine, ΔPhe, is the most commonly studied α,β-dehydroamino acid. In nature, further modifications of the α,β-dehydroamino acids were found, for example, replacement of the C-terminal amide group by oxazole ring. The conformational properties of oxazole-dehydrophenylalanine residue (ΔPhe-Ozl), both isomers Z and E, were investigated. To determine all possible conformations, theoretical calculations were performed using Ac-(Z/E)-ΔPhe-Ozl(4-Me) model compounds at M06-2X/6-31++G(d,p) level of theory. Ac-(Z/E)-ΔPhe-Ozl-4-COOEt compounds were synthesized and the conformational preferences of each isomer, Z and E, were investigated using FTIR and NMR-NOE in solutions of increasing polarity (CHCl3 , DMSO-d6). The solid-state low-temperature structures of Ac-(Z)-ΔPhe-Ozl-4-COOEt and its intermediate analog Ac-(Z)-ΔPhe-Ozn(4-OH)-4-COOEt were also determined. In a weakly polar environment, the ΔPhe-Ozl residue has a tendency to adopt the conformation β2 with the calculated φ and ψ angles of -127° and 0° for the isomer Z and -170° and 26° for the isomer E. The increase of environment polarity favors the helical conformation α and the beta-turn like conformation β, but the conformation β2 seems to be still accessible. The (E)-ΔPhe-Ozl residue can be obtained from the isomer Z in photoisomerization reaction. However, hydroxyl-oxazoline-dehydrophenylalanine ΔPhe-Ozn(4-OH) decomposes in such conditions. Alternatively, (E)-ΔPhe-NH2 can be applied as a substrate in the Hantzsch reaction. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 283-294, 2016.
authors.affiliation: Faculty of Chemistry, University of Opole, Oleska 48, Opole, 45-052, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Staś
authors.affiliation: Faculty of Chemistry, University of Opole, Oleska 48, Opole, 45-052, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Bujak
authors.affiliation: Faculty of Chemistry, University of Opole, Oleska 48, Opole, 45-052, Poland.
authors.forename: Małgorzata A
authors.initials: MA
authors.lastname: Broda
authors.affiliation: Faculty of Chemistry, University of Opole, Oleska 48, Opole, 45-052, Poland.
authors.forename: Dawid
authors.initials: D
authors.lastname: Siodłak
mesh_terms: D002725:Chloroform / Q000737:chemistry; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008968:Molecular Conformation; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D055668:Photochemical Processes; D011789:Quantum Theory; D012996:Solutions; D012997:Solvents / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism
chemical_list: D010080:Oxazoles; D012996:Solutions; D012997:Solvents; D010649:Phenylalanine; C018632:phenyldehydroalanine; D002725:Chloroform; D004121:Dimethyl Sulfoxide
keywords: Hantzsch reaction; Ramachandran diagram; cis-trans isomerization; dehydroamino acids; photoisomerization