Synthesis of Δ E Phe‐containing tripeptide via photoisomerization and its conformation in solution

A new synthetic route to (E)‐β‐phenyl‐α,β‐dehydroalanine (Δ E Phe)‐containing peptide was presented via photochemical isomerization of the corresponding (Z)‐β‐phenyl‐α,β‐dehydroalanine (Δ Z Phe)‐containing peptide. By applying this method to Boc–Ala–Δ Z Phe–Val–OMe ( Z‐I : Boc, t ‐butoxycarbonyl; OMe, methoxy), Boc–Ala–Δ E Phe–Val–OMe ( E‐I ) was obtained. The identification of peptide E‐I was evidenced by 1 H‐nmr, 13 C‐nmr, and uv absorption spectroscopy, elemental analysis, and hydrogenation. The conformation of peptide E‐I in CDCl 3 was investigated by 1 H‐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, Δ E Phe NH and Val NH, participate in intramolecular hydrogen bonding. In both peptides, a remarkable NOE (∼11–13%) was observed for Ala C α 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(Δ E Phe), and between CO(Ala) and NH(Val) as its plausible conformation. © 2000 John Wiley & Sons, Inc. Biopoly 53: 484–496, 2000