DESIGN OF PEPTIDES - SYNTHESIS, CRYSTAL-STRUCTURE, MOLECULAR-CONFORMATION, AND CONFORMATIONAL CALCULATIONS OF N-BOC-L-PHE-DEHYDRO-ALA-OCH3

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-OCH3 (C18H24N2O5) was synthesized by the usual workup procedure and finally by converting N-Boc-L-Phe-L-Ser-OCH3 to N-Boc-L-Phe-dehydro-Ala-OCH3. 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) angstrom, b = 5.195(3) angstrom, c = 19.563(3) angstrom, beta = 94.67(5)-degrees, V = 970.1(6) angstrom3, 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 C2-alpha-C2-beta distance is 1.327(8) angstrom, while the bond angles N2-C2-alpha-C2' and C1'-N2-C2-alpha are 109.8(5)-degrees and 127.8(5)-degrees, respectively. The backbone adopts a nonspecific conformation with dehydro-Ala in a fully extended conformation with the following torsion angles: theta-1 = 175.2(4)-degrees, omega-0 = 170.2(4)-degrees, phi-1 = 135.8(5)-degrees, psi-1 = -22.6(6)-degrees, omega-1 = 168.5(5)-degrees, phi-2 = -170.3(5)-degrees, psi-2T = -178.6(5)-degrees, theta(T) = 178.4(7)-degrees. 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 chi-1 = 63.3(6)-degrees, chi-1(2,1) = -92.1(6)-degrees, chi-1(2,2) = 89.5(6)-degrees. 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---O2 of distance 2.938(7) angstrom 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.