Benzyl N-[(S)-2-hydroxy-1-({[(E)-2-hydroxy-4-methoxybenzylidene]hydrazinyl}carbonyl)ethyl]carbamate

The shape of the title compound, C19H21N3O6, is curved with the conformation about the imine bond [1.291 (3) Å] being E. While the hydroxy-substituted benzene ring is almost coplanar with the hydrazinyl residue [N—N—C—C = 177.31 (18)°], an observation correlated with an intramolecular O—H⋯N hydrogen bond leading to an S(6) ring, the remaining residues exhibit significant twists. The carbonyl residues are directed away from each other as are the amines. This allows for the formation of O—H⋯O and N—H⋯O hydrogen bonds in the crystal, which lead to two-dimensional supramolecular arrays in the ac plane. Additional stabilization to the layers is afforded by C—H⋯π interactions.

The use of the EPSRC X-ray crystallographic service at the University of Southampton, England, and the valuable assistance of the staff there is gratefully acknowledged. JLW acknowledges support from CAPES (Brazil). Comment Several L-serine derivatives have been found to have potential in anti-tumour therapy, for example, conagenin, a naturally occurring serine derivative, was shown to improve the anti-tumour efficacy of adriamycin and mitomycin C against murine leukemias (Jiao et al., 2009;Yakura et al., 2007). Other L-serine derivatives reported as potential new anti-tumour agents include the anti-biotic thrazarine, which sensitizes tumour cells to macrophage-mediated cytolysis (Takahashi et al., 1988), and eponemycin, an immunomodulator, which plays a crucial role in tumour progression and metastases by supplying essential nutrients to B16 melanoma cells (Sin et al., 1998).
Although the absolute structure of (I), Fig. 1, could not be determined experimentally, the assignment of the S-configuration at the C10 atom is based on a starting reagent. Overall, the molecule of (I) is curved. The 2-hydroxy-4-methoxyphenyl group is planar [the C7-O2-C4-C3 torsion angle is -1.2 (3) °] and the planarity extends to include the hydrazino residue In the crystal packing, the O4-hydroxyl group forms an O-H···O hydrogen bond with the carbonyl-O3 atom adjacent to the hydrazino residue, Table 1. Each of the N-H atoms form a N-H···O hydrogen bond: N2 to the O4-hydroxyl group and N3 to the O5-ester atom, Table 1. This results in the formation of supramolecular layers in the ac plane, Fig. 2. Additional stabilization to the layers is afforded by C-H···π interactions, Table 1
The O-and N-bound H atoms were located from a difference map and refined with the distance restraint O-H = 0.84 ± 0.01 and N-H = 0.86±0.01 Å, and with U iso (H) = zU eq (carrier atom); z = 1.5 for O and z = 1.2 for N. In the absence of significant anomalous scattering effects, 1934 Friedel pairs were averaged in the final refinement. However, the absolute configuration was assigned on the basis of the chirality of the L-serine starting material. In the final refinement two reflections exhibiting poor agreement were omitted, i.e. (001) and (011). Fig. 1. The molecular structure of (I) showing displacement ellipsoids at the 50% probability level.

Special details
Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'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 > 2σ(F 2 ) is used only for calculating Rfactors(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.