Crystal structure of N-{N-[N-(tert-butoxycarbonyl)-l-α-aspartyl]-l-α-aspartyl}-l-α-aspartic acid 14,24,34-trimethyl ester 31-2-oxo-2-phenylethyl ester {Boc-[Asp(OMe)]3-OPac}

In the title homotripeptide of l-aspartic acid β-methyl ester [Asp(OMe)], all peptide bonds adopt an s-trans conformation with respect to the N—H and C=O groups. In the crystal, N—H⋯O hydrogen bonds result in an infinite parallel β-sheet structure.


Figure 1
The molecular structure of the title compound with displacement ellipsoids drawn at the 50% probability level. The minor component of the disordered group is drawn with dashed lines. Table 1 Selected torsion angles ( ). Name Atoms Torsion angle

Synthesis and crystallization
The synthesis of the title homotripeptide, 6, was performed according to the scheme in Fig. 4. Compound 1 was synthesized from l-aspartic acid according to a previously described method (Reddy et al., 2011;Ollivier et al., 2010) Compound 2 was synthesized according to a slightly modified literature procedure (Wang et al., 1977). Compound 1 (7.05 g, 28.5 mmol) was dissolved in MeOH (20 mL) and 0.7 M aqueous Cs 2 CO 3 solution (20 ml) was added. The mixture was evaporated to dryness and the residue was reevaporated three times with EtOH. A mixture of the white solid cesium salt and phenacyl bromide (5.68 g, 28.5 mmol) in DMF (30 mL) was stirred for 15min, and the precipitated cesium bromide removed. The solution was evaporated to give the residue, which was diluted with ethyl acetate, washed with water, sat. aqueous NaHCO 3 , and dried over Na 2 SO 4 . The drying agent was filtered off and the filtrate evaporated under reduced pressure. Crystallization of the product from a mixture of ethyl acetate and hexane afforded colourless crystals. Yield 5.36 g (14.7 mmol, 51.5% Compound 3: Compound 2 (0.67 g, 2.72 mmol) was treated with 4.0 M HCl in dioxane for 60 min. The excess of HCl and solvent were evaporated and the residue was re-evaporated three times with MeOH, which was used for the next reaction without purification.

Figure 3
A packing diagram of the title compound viewed approximately along the b axis, showing the C-HÁ Á ÁO hydrogen bonds between the -sheets (blue dashed lines). Only the major disorder component is shown.
[Symmetry codes: (iii) Àx, y + 1 evaporated three times with MeOH, which was used for the next reaction without purification.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. The Boc protecting group at the Nterminus of the peptide is disordered. The final occupancy ratio is 0.504 (5):0.496 (5). The C atoms of the disordered tertbutyl groups were refined with SIMU restraints and the C5-O5A and C5-O5B bonds were treated with DFIX restraints of 1.21 (1) Å . The N-bound H atoms were refined freely, while the other H atoms were placed in geometrically idealized positions (C-H = 0.95-1.00 Å ) and refined as riding on their parent atoms, with U iso (H) = 1.2U eq (C) (or 1.5U eq (C) for the methyl groups). The absolute configuration was known for the synthesized material.

N-{N-[N-(tert-butoxycarbonyl)-L-α-aspartyl]-L-α-aspartyl}-L-α-aspartic acid 1 4 ,2 4 ,3 4 -trimethyl ester 3 1 -2-oxo-2phenylethyl ester
Crystal data Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.