Crystal structure of the tripeptide N-(benzyloxycarbonyl)glycylglycyl-l-norvaline

The title tripeptide, C17H23N3O6, contains a nonproteinogenic C-terminal amino acid residue, norvaline, which is an isomer of the amino acid valine. Norvaline, unlike valine, has an unbranched side chain. The molecule has a Gly–Gly segment which adopts an extended conformation. The norvaline residue also adopts an extended backbone conformation while its side chain has a g + t conformation. In the crystal lattice, N—H⋯O and O—H⋯O hydrogen bonds stabilize the packing. Molecules translated along the crystallographic a axis associate through an N—H⋯O hydrogen bond. The remaining three hydrogen bonds are between molecules related by a 2 1 screw axis.


S1. Chemical context
Norvaline is a non-proteinogenic aminoacid with an unbranched side chain. It is an isomer of the branched chain aminoacid valine. It is postulated that norvaline has been an abundant protein component during primitive stages of cell evolution (Alvarez-Carreño et al., 2013). Norvaline is formed as a byproduct during isoleucine fermentation from threonine by Serratia marcescens (Kisumi, Sugiura & Chibata, 1976;Kisumi, Sugiura, Kato & Chibata, 1976). The title peptide contains a Gly-Gly segment. This structural study was undertaken as part of an endeavour to understand the conformational flexibility of consecutive glycine segments in short peptides. Due to the conformational freedom of glycine residues they are increasingly found in turns (Ramakrishnan & Srinivasan, 1990). In various polymorphic forms of Tyr-Gly-Gly-Phe-Leu, the Gly-Gly segment adopts extended conformation, type-I′ β-turn and 3 10 helical structures (Karle et al., 1983;Smith & Griffin, 1978;Aubry et al., 1989). This demonstrates the conformational flexibility of consecutive glycine sequences.

S3. Supramolecular features
The packing in the crystal structure is stabilized by four intermolecular hydrogen bonds (Table 1). Molecules translated along the crystallographic a axis associate through a N-H···O hydrogen bond. The remaining three hydrogen bonds are between molecules related by a 2 1 screw axis.

S4. Synthesis and crystallization
The title compound was purchased commercially. Needle-shaped crystals of the title compound were obtained by slow evaporation from methanol/water (1:1 v/v) solution.

S5. Refinement
The H-atoms bonded to N3 and C3A could be located from a difference Fourier map and refined freely. The remaining Hatoms were fixed geometrically in calculated positions and included in the refinement using a riding model isotropic displacement parameters U iso for hydrogen atoms were set at 1.5 times the U eq of the carrier atoms in case of methyl groups and hydroxyl groups. In case of hydrogens attached to aromatic carbons, methylene carbons and nitrogen atoms, U iso was set at 1.2 times the U eq of the carrier atoms. The anisotropic displacement parameters of the carbon atoms C3A, C3B, C3C and C3D were restrained to be equal within a standard uncertainty of 0.01Å 2 using the DELU command in SHELXL97 (Sheldrick, 2008). In the absence of significant anomalous scattering effects, 1967 Friedel pairs were merged. The absolute configuration was known for the purchased material. The relatively high value of Rint (0.12) is due to the poor quality of the crystal available.

Figure 1
Thermal ellipsoid plot of the title compound drawn at the 50% probability level. Hydrogen atoms are omitted for clarity.

Special details
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.