Synthesis of ΔEPhe-containing tripeptide via photoisomerization and its conformation in solution

Abstract

A new synthetic route to (E)‐β‐phenyl‐α,β‐dehydroalanine (ΔEPhe)‐containing peptide was presented via photochemical isomerization of the corresponding (Z)‐β‐phenyl‐α,β‐dehydroalanine (ΔZPhe)‐containing peptide. By applying this method to Boc–Ala–ΔZPhe–Val–OMe (Z‐I: Boc, t‐butoxycarbonyl; OMe, methoxy), Boc–Ala–ΔEPhe–Val–OMe (E‐I) was obtained. The identification of peptide E‐I was evidenced by 1H‐nmr, 13C‐nmr, and uv absorption spectroscopy, elemental analysis, and hydrogenation. The conformation of peptide E‐Iin CDCl3 was investigated by 1H‐nmr spectroscopy (solvent dependence of NH chemical shift and difference nuclear Overhauser effect). Interestingly, peptide E‐I differed from peptide Z‐I in the hydrogen‐bonding mode. Namely, for peptide Z‐I, only Val NH participates in intramolecular hydrogen bonding, which leads to a type II β‐turn conformation supported by hydrogen bonding between CO(Boc) and NH(Val). On the other hand, for peptide E‐I, two NHs, ΔE Phe NH and Val NH, participate in intramolecular hydrogen bonding. In both peptides, a remarkable NOE (∼11–13%) was observed for Ala Cα H–ΔPhe NH pair. Based on the nmr data and conformational energy calculation, it should be concluded that peptide E‐I takes two consecutive γ‐turn conformations supported by hydrogen bonding between CO(Boc) and NH(ΔEPhe), and between CO(Ala) and NH(Val) as its plausible conformation. © 2000 John Wiley & Sons, Inc. Biopoly 53: 484–496, 2000

Structural and conformational properties of (Z)-?-(1-naphthyl)- dehydroalanine residue

“…The product was purified by recrystallization from ethyl acetate/n-hexane. Peptide 2 showed no minor peaks, 25 suggesting its diastereomer in the 1 H NMR spectra, but marked CD signals ([] 310 ϭ 4.0 ϫ 10 4 in CHCl 3 ), indicating that the combination of saponification and fragment condensation processes leads to no racemization essentially. Yield 1.29 g (81 %); mp 126 -130°C; …”

“…The program PEPCON, written by M. Sisido (private communication) for a conformational energy calculation 29 and graphics 32 of a given peptide, was modified to be applicable to ␤-aryldehyroalanine-containing peptides. [23][24][25][33][34][35][36] …”

Kinetics of photochemical isomerization of TFA-Gly-ZΔPhe into TFA-Gly-EΔPhe

“…These progression curves were analyzed by applying standard kinetic equations, 21 which unequivocally indicated that the studied reaction is of the first order, with k1 value of (12.43 ± 0.27)×10 Preparative conversion of substituted Z ΔPhe into E ΔPhe, 22 as well as such isomerization of this dehydroamino acid in several peptides has been described previously. 23,24 However, these papers, dedicated to the photochemical reactions of slightly different aromatic dehydroamino acids, state that this process is not so simple and is accompanied by variable photochemical cyclizations. 25,26 Our study, however, does not indicate the presence of any other products than Gly-E ΔPhe in the case of this photochemical reaction, and no cyclization products were found even after long irradiation of reaction mixture, irrespective of which analytical method was used.…”

A helical arrangement of ?-substituents of dehydropeptides: Synthesis and conformational study of sequential nona- and dodecapeptides possessing (Z)-?-(1-naphthyl)dehydroalanine residues

“…14 The program PEP-CON 30,31 for a conformational energy calculation and graphics of a given peptide was modified to be applicable to ␤-aryldehyroalanine-containing peptides. [32][33][34][35] The stepwise elongation 36,37 of the repeating unit -(Ala-⌬ Z Nap-Leu)-was used to find the stable conformations from all possible candidates. In the first step, energy minimization of the tripeptide, Ac-Ala-⌬ Z Nap-Leu-OMe (Ac ϭ acetyl), was carried out.…”