4-Nitro-N-phthalyl-l-tryptophan

The crystal structure of the title compound [systematic name: (2R)-3-(1H-indol-3-yl)-2-(4-nitro-1,3-dioxoisoindolin-2-yl)propanoic acid], C19H13N3O6, an analogue of epigenetic modulator RG108, is constrained by strong hydrogen bonds between the indole N—H group and a carbonyl O atom of the phthalimide ring of a symmetry-related molecule, and between the protonated O atom of the carboxyl group and a carbonyl O atom of the phthalimide ring. π–π stacking interactions with centroid–centroid distances of 3.638 (1) and 3.610 (1) Å are also observed between indole and phthalimide rings.

The crystal structure of the title compound [systematic name: (2R)-3-(1H-indol-3-yl)-2-(4-nitro-1,3-dioxoisoindolin-2-yl)propanoic acid], C 19 H 13 N 3 O 6 , an analogue of epigenetic modulator RG108, is constrained by strong hydrogen bonds between the indole N-H group and a carbonyl O atom of the phthalimide ring of a symmetry-related molecule, and between the protonated O atom of the carboxyl group and a carbonyl O atom of the phthalimide ring.stacking interactions with centroid-centroid distances of 3.638 (1) and 3.610 (1) Å are also observed between indole and phthalimide rings.

Related literature
For crystallographic information and details about the RG108 analogue, see: Braun et al. (2010) and details of the biological evaluation, see: Brueckner et al. (2005).
Two main types of H-bonding interactions are observed in the structure: one between N-H of the indole ring (N2) and O1 of the phtalimide ring, and the other between the protonated oxygen (O4) from the carboxylic moiety and O2 from the phtalimide ring (see Table 1).
In addition to H-bonds, crystal packing organization is further stabilized by π-π-stacking interactions involving symmetry-related molecules, in particularly between the 6-membered coupled rings of nitrophthalimide and indole moiety (see Table 2). No interactions of this type are present in the packing of the dicyclohexylamine salt of RG108 (Braun et al. (2010), because of the presence of the ammonium counter-cation and water molecules included in the crystalline network.
In contrast to the structure of the dicyclohexylamine salt of RG108 (Braun et al. (2010)), where the compound conformation is constrained by strong (charge-assisted) H-bonds with the dicyclohexylammonium ion and extra water molecules, the angle between the two fused rings is 14.23 (4)° in the present structure compared to 58.35 (4)° in the case of the RG108 salt. The torsion angle of the chain between the two aromatic moieties (N1-C9-C10-C11) is also distinct: -155.66 (17)°a nd -61.93 (17) ° for the title and RG108 salt structures, respectively.

Experimental
Synthesis of the compound was accomplished by micro-wave heating of L-tryptophan (1 mmol, 204 mg) and 4-nitro phthalic anhydride (1 mmol, 193 mg) in 5 ml of DMF. The mixture was then poured in cold aqueous buffer solution (pH = 2) and extracted with ethyl acetate. After drying with Na 2 SO 4 , the organic phase is evaporated and the residue is purified by flash chromatography (dichloromethane and methanol: 9/1; yield = 60%, 230 mg).

Refinement
H1 and H2, bound to O4 and N2 respectively and involved in hydrogen bonds, were located from ΔF Fourier difference maps and their position refined freely. All other remaining H-atoms were placed at idealized positions and allowed to ride on their parent atoms, with C-H distances of 0.93 -0.98 Å and with U iso (H) = 1.2U eq (C).