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.

Insight into the Structure of Victorin, the Host-Selective Toxin from the Oat PathogenCochliobolus victoriae. Studies of the Unique Dehydroamino Acid β-Chlorodehydroalanine

“…To complete the preparation of β-chlorodehydroalanine model structures, the isomerization from the isomers Z into E assisted by UV irradiation was performed. The photoisomerization Z / E of simple dehydroamino acid residues is known. , However, according to the best of our knowledge, the application of this reaction to the β-halogenodehydroalanyl residue is reported for the first time here. The optimal reaction conditions in this case include the irradiation of the reaction mixture with UV light with a maximum wavelength of 366 nm at 5 h with an intensity of 400–440 μW/cm 2 (Figure d).…”

Thiazole–amino acids: influence of thiazole ring on conformational properties of amino acid residues

“…In our previous studies, we have analysed the conformational properties of oxazole–amino acid for analogous residues (Siodłak et al 2014a ; Staś et al 2016b ). Comparison of the relative energy of oxazole– and thiazole–amino acid conformers with the same side chain (Fig.…”

“…Previous studies have shown that modifications of peptide main chain or side chain as N -methylation (Siodłak et al 2006 , 2008 , 2012 ; Broda et al 2005 , 2009 ), C -terminal ester bond (Siodłak et al 2010 , 2011 ; Siodłak and Janicki 2010 ), dehydration of side chain (Buczek et al 2014 ), cyclization (Staś et al 2016a ), and many more (Jwad et al 2020 ; Gil et al 2009 ; Paranthaman 2018 ) have a considerable influence on preferred conformation. This includes the introduction of a five-membered heterocycle, such as oxazole (Siodłak et al 2014a ; Staś et al 2016a , b ) or thiazole, into a peptide main chain as an isosteric replacement of amide group. Peptides that contain heterocyclic amide isosteres are usually more rigid than the corresponding homodetic cyclic peptide (Jwad et al 2020 ; Abbenante et al 1996 ).…”

Imidazole-amino acids. Conformational switch under tautomer and pH change

“…Azole rings can be also used as trans replacement agents (Kaczmarek et al 2021;Lenartowicz et al 2022). Our previous studies show that the amino acid residues containing azole rings in the main chain possess unusual conformational properties (Siodłak et al 2014b;Staś et al 2026aStaś et al , 2016bStaś et al , 2021. Thiazole and oxazole amino acids tend to adopt the unique semi-extended conformation β2 (φ, ψ ≈ 180°, 0°), especially in weakly polar environments, where this global conformation is stabilized through the formation of the internal N-H•••N hydrogen bond, atypical for standard residues.…”