Synthesis, crystal structure, and molecular conformation of N-Boc-L-Phe-dehydro-Leu-L-Val-OCH₃

Abstract

The peptide N-Boc-L-Phe-dehydro-Leu-L-Val-OCH₃ was synthesized by the usual workup procedure and finally by coupling the N-Boc-L-Phe-dehydro-Leu-OH to valine methyl ester. It was crystallized from its solution in methanol-water mixture at 4°C. The crystals belong to the triclinic space group P1 with a = 5.972(5) Å, b = 9.455(6) Å, c = 13.101(6) Å, α= 103.00(4)°, β =97.14(5)°, γ = 102.86(50)°, V = 690.8(8) Å, Z = 1, dm = 1.179(5) Mg m⁻³ and dc = 1.177(5) Mg m⁻³. The structure was determined by direct methods using SHELXS86. It was refined by block-diagonal least-squares procedure to an R value of 0.060 for 1674 observed reflections. The C^α₂-C^β₂ distance of 1.323(9) Å in dehydro-Leu is an appropriate double bond length. The bond angle C^α-C^β-C^γ; in the dehydro-Leu residue is 129.4(8)°. The peptide backbone torsion angles are θ ¹ = −168.6(6)°, ω₀ = 170.0(6)°, Φ₁ = −44.5(9)°, ψ₁ = 134.5(6)°, ω₁ = 177.3(6)°, Φ₂ = 54.5(9)°, ψ₂^T₃ = 31.1(10)°, ω₂ = 171.7(6)°, Φ₃ = 51.9(8)°, ψ = 139.0(6)°, θ^T =-175.7(6)°. These values show that the backbone adopts a β -turn II conformation. As a result of β-turn, an intramolecular hydrogen bond is formed between the oxygen of the ith residue and NH of the (i + 3)th residue at a distance of 3.134(6) Å. The Boc group has a trans-trans conformation. The side-chain torsion angles of the Phe residue are χ₁ = 171.6(6)°, χ^2,1₁ = −102.1(9)°, and χ^2,2₁ = 78.6(10)°. The side-chain conformational angles of dehydro-Leu residue are χ ₂ = 2.7(13)°, χ^2,1₂ = −107.3(11)°, and χ^2,2₂; = 131.3(10)°. The torsion angles χ^1,1₃ and χ^1,2₃; that define the conformation of the valyl side chain are -166.16(6)° and 69.1(9)°, respectively. The crystal structure is stabilized by hydrogen bonds along the a and b axes, while the van der Waals forces are the stabilizing interactions in the c direction.