Design of peptides: Synthesis, crystal structure, molecular conformation, and conformational calculations of N‐Boc‐<scp>L</scp>‐Phe‐Dehydro‐Ala‐OCH₃

Abstract

Abstract It is noteworthy that the dehydro‐Ala residue adopts an extended conformation that is different than those observed in dehydro‐Phe, dehydro‐Leu, and dehydro‐Abu. The peptide N‐Boc‐ L ‐Phe‐dehydro‐Ala‐OCH 3 (C 18 H 24 N 2 O 5 ) was synthesized by the usual workup procedure and finally by converting N‐Boc‐ L ‐Phe‐ L ‐Ser‐OCH 3 to N‐Boc‐ L ‐Phe‐dehydro‐Ala‐OCH 3 . It was crystallized from its solution in a methanol–water mixture at room temperature. The crystals belong to the monoclinic space group P2 1 with a = 9.577(1) Å, b = 5.195 (3) Å, c = 19.563 (3) Å, β = 94.67 (5)°, V = 970.1(6) Å 3 , Z = 2, d m = 1.201(5) Mg m −3 , d c = 1.197 (5) Mg m −3 . The structure was determined using direct method procedures. It was refined by a full‐matrix least‐squares procedure to an R value of 0.048 for 1370 observed reflections. The C ‐C distance is 1.327 (8) Å, while the bond angles N2‐C ‐C and C ‐N2‐C are 109.8 (5)° and 127.8 (5)°, respectively. The backbone adopts a nonspecific conformation with dehydro‐Ala in a fully extended conformation with the following torsion angles: θ l = 175.2 (4)°, ω, 0 = 170.2 (4)°, ø 1 = 135.8 (5)°, ψ 1 = ‐22.6(6)°, ω 1 = 168.5 (5)°, ψ 2 ,= ‐170.3(5)°, ψ = –178.6(5)°', θ T = 178.4(7)°. The rigid planar and trans conformation of dehydro‐Ala forces Phe to adopt a strained conformation. The Boc group has a trans‐trans conformation. The side‐chain torsion angles of the Phe residue are χ 1 = 63.3(6)°, χ = −92.1(6)°, χ 1 2,2 = 89.5 (6)°. The observed conformation is stabilized by three nonlinear intramolecular C—H‐‐‐O type of interactions. The crystal structure is stabilized by an intermolecular hydrogen bond N1—H1‐‐‐O 2 of distance 2.938(7) Å along the b axis while the van der Waals forces are the stabilizing interactions in the ac plane. The low‐energy conformation found by calculations corresponds to the solid state conformation established by the crystal structure analysis. © 1992 John Wiley &amp; Sons, Inc.