Synthesis of mutual azo prodrugs of anti-inflammatory agents and peptides facilitated by α-aminoisobutyric acid.

Reported is the synthesis of azo mutual prodrugs of the nonsteroidal anti-inflammatory agents (NSAIDs) 4-aminophenylacetic acid (4-APAA) or 5-aminosalicylic acid (5-ASA) with peptides, including an antibiotic peptide temporin analogue modified at the amino terminal by an α-aminoisobutyric acid (Aib) residue. These prodrugs are designed for colonic delivery of two agents to treat infection and inflammation by the bacterial pathogen Clostridium difficile .

N,N'-(Phenyl-imino-dimethyl-ene)di-prop-2-enamide hemihydrate.

In the title compound, C(14)H(17)N(3)O(2)·0.5H(2)O, the asymmetric unit consists of an N,N'-(phenyl-imino-dimethyl-ene)diprop-2-enamide mol-ecule and one half-mol-ecule of water, with the O atom of the latter having 2 site symmetry. The supra-molecular architecture is framed by the inter-play of two-dimensional networks of both O-H⋯O and N-H⋯O inter-actions supported by C-H⋯O and edge-to-face C-H⋯π inter-actions.

6,8-Dibromo-5-hydr-oxy-4-oxo-2-phenyl-4H-chromen-7-yl acetate.

In the title compound, C(17)H(10)Br(2)O(5), the chromene ring is almost planar with minimal puckering [total puckering amplitude = 0.067 (4) Å]. The dihedral angle between chromeme ring system and phenyl ring is 3.

5,7-Dimeth-oxy-2-phenyl-4H-chromen-4-one.

The asymmetric unit of the title compound, C(17)H(14)O(4), contains two independent mol-ecules which differ in the relative orientations of the phenyl rings with repect to the essentially planar [maximum deviations of 0.029 (2) and 0.050 (2) Å in the two mol-ecules] chromene fused-ring system, forming dihedral angles of 10.

Dimethyl 2,2'-[(4-oxo-2-phenyl-4H-chromene-5,7-di-yl)di-oxy]diacetate: a less densely packed polymorph.

The title mol-ecule, C(21)H(18)O(8), crystallizes in two crystal polymorphs, see also Nallasivam, Nethaji, Vembu & Jaswant [Acta Cryst. (2009), E65, o312-o313]. The main difference between the two polymorphs is in the conformation of the oxomethyl-acetate groups with regard to the almost planar [total puckering amplitude 0.

Dimethyl 2,2'-[(4-oxo-2-phenyl-4H-chromene-5,7-diyl)dioxy]diacetate: a more densely packed polymorph.

The title mol-ecule, C(21)H(18)O(8), crystallizes in two crystal polymorphs, see also Nallasivam, Nethaji, Vembu & Jaswant [Acta Cryst. (2009), E65, o314-o315]. The mol-ecules of both polymorphs differ by the conformation of the oxomethyl-acetate groups.

2,4-Dichloro-phenyl 4-bromo-benzene-sulfonate.

In the title mol-ecule, C(12)H(7)BrCl(2)O(3)S, the dihedral angle between the two benzene rings is 55.18 (5)°. The notable inter-molecular contacts include C-H⋯O and π-π inter-actions [centroid-centroid distances = 4.

4-Nitro-phenyl 4-bromo-benzene-sulfonate.

In the title mol-ecule, C(12)H(8)BrNO(5)S, the dihedral angle between the two benzene rings is 30.02 (7)°. The crystal structure is stabilized by weak C-H⋯O inter-actions.

Morpholinium 2,4,6-trinitro-phenolate.

There are two independent formula units in the asymmetric unit of the title compound, C(4)H(10)NO(+)·C(6)H(2)N(3)O(7) (-). The morpholinium cations in both mol-ecules are puckered and adopt a chair conformation. Intermolecular N-H⋯O and C-H⋯O inter-actions generate rings of motifs R(2) (1)(5) and R(1) (2)(6).

N,N-Dimethyl-anilinium 2,4,6-trinitro-phenolate.

In the title compound, C(8)H(12)N(+)·C(6)H(2)N(3)O(7) (-), there are N-H⋯O and C-H⋯O inter-actions which generate R(2) (1)(5), R(2) (1)(6) and R(1) (2)(6) ring motifs. The supra-molecular aggregation is completed by the presence of edge-to-face and offset face-to-face π-π inter-actions with centroid-centroid distances of 3.673 and 3.

2-Phenyl-5,7-bis-(prop-2-en-1-yl-oxy)-4H-chromen-4-one.

In the title compound, C(21)H(18)O(4), tthe dihedral angle between the chromene ring system and the pendant phenyl ring is 6.1 (1)°. The crystal structure is stabilized by an intermolecular C-H⋯O and C-H⋯π inter-actions.

5,7-Bis(benz-yloxy)-2-phenyl-4H-chromen-4-one.

In the title compound, C(29)H(22)O(4), the chromene ring is almost planar with a small puckering [0.143 (2) Å]. The crystal structure is stabilized by C-H⋯O and C-H⋯π inter-actions.

4-Meth-oxy-5-[4-(4-meth-oxy-1,3-benzodioxol-5-yl)perhydro-1H,3H-furo[3,4-c]furan-1-yl]-1,3-benzodioxole.

The 1,3-benzodioxole ring systems in the title compound, C(22)H(22)O(8), are almost planar. The perhydro-furofuranyl system linking them adopts a distorted double-envelope conformation. Supra-molecular aggregation is effected by C-H⋯O, C-H⋯π and π-π [centroid-centroid distance of 3.

Benzyl N-[2-(1H-indol-3-yl)eth-yl]dithio-carbamate.

The indole and phenyl ring systems in the title compound, C(18)H(18)N(2)S(2), are nearly coplanar, the indole and phenyl planes forming a dihedral angle of 6.5 (1)°. Supra-molecular aggregation is effected by N-H⋯S, C-H⋯S, N-H⋯π and C-H⋯π inter-actions.

Layer architecture in 4-nitrophenyl and 4-chlorophenyl 3-nitrobenzenesulfonate at 100 K.

The structures of the title compounds, C(12)H(8)N(2)O(7)S and C(12)H(8)ClNO(5)S, contain weak C-H.O interactions creating layers of molecules which, taking the conformation of the molecules into account, are arranged in an ABAB sequence. Both structures can be designated, therefore, as ordered racemates of rotameric species.

2-Chlorophenyl 3-nitrobenzenesulfonate and 2,4-dichlorophenyl 3-nitrobenzenesulfonate: supramolecular aggregation through C-H...O, pi-pi and van der Waals interactions.

In 2-chlorophenyl 3-nitrobenzenesulfonate, C(12)H(8)ClNO(5)S, and 2,4-dichlorophenyl 3-nitrobenzenesulfonate, C(12)H(7)Cl(2)NO(5)S, weak C-H...