Molecular Structures of Isomeric Ortho, Meta, and Para Bromo-Substituted α-Methylsulfonyl-α-diethoxyphosphoryl Acetophenones by X-ray and DFT Molecular Orbital Calculations.

The X-ray single crystal analysis of isomeric ortho, meta, and para bromo-substituted α-methylsulfonyl-α-diethoxyphosphoryl acetophenones showed that this class of compound adopts synclinal (gauche) conformations for both [-P(O)(OEt)2] and [-S(O)2Me] groups, with respect to the carbonyl functional group. The phosphonate, sulfonyl, and carbonyl functional groups are joined through an intramolecular network of attractive interactions, as detected by molecular orbital calculations at the M06-2X/6-31G(d,p) level. These interactions are responsible for the more stable conformations in the gas phase, which also persist in the solid-state structures. The main structural distinction in the title compounds relates to the torsion angle of the aryl group (with respect to the carbonyl group), which gives rise to different interactions in the crystal packing, due to the different positions of the Br atom.

Triterpenoids as novel natural inhibitors of human cathepsin L.

Cathepsins L (catL) and B play an important role in tumor progression and have been considered promising therapeutic targets in the development of novel anticancer agents. Using a bioactivity-guided fractionation, a series of triterpenoids was identified as a new class of competitive inhibitors towards cathepsin L with affinity values in micromolar range. Among the 14 compounds evaluated, the most promising were 3-epiursolic acid (3), 3-(hydroxyimino)oleanolic acid (9), and 3-(hydroxyimino)masticadienoic acid (13) with IC50 values of 6.5, 2.4, and 2.6 µM on catL, respectively. Most of the evaluated triterpenoids do not inhibit cathepsin B. Thus, the evaluated compounds exhibit a great potential to help in the design of new inhibitors with enhanced potency and affinity towards catL. Docking studies were performed in order to gain insight on the binding mode and SAR of these compounds.

Crystal structure of (3E)-3-[(4-nitro-phen-oxy)-meth-yl]-4-phenyl-but-3-en-2-one.

In the title compound, C17H15NO4, the conformation about the C=C double bond [1.348 (2) Å] is E with the ketone group almost co-planar [C-C-C-C torsion angle = 7.2 (2)°] but the phenyl group twisted away [C-C-C-C = 160.93 (17)°]. The terminal aromatic rings are almost perpendicular to each other [dihedral angle = 81.61 (9)°] giving the mol-ecule an overall U-shape. The crystal packing feature benzene-C-H⋯O(ketone) contacts that lead to supra-molecular helical chains along the b axis. These are connected by π-π inter-actions between benzene and phenyl rings [inter-centroid distance = 3.6648 (14) Å], resulting in the formation of a supra-molecular layer in the bc plane.

Crystal structure of (3E)-3-(2,4-di-nitro-phen-oxy-meth-yl)-4-phenyl-but-3-en-2-one.

In the title compound, C17H14N2O6, the conformation about the C=C double bond [1.345 (2) Å] is E, with the ketone moiety almost coplanar [C-C-C-C torsion angle = 9.5 (2)°] along with the phenyl ring [C-C-C-C = 5.9 (2)°]. The aromatic rings are almost perpendicular to each other [dihedral angle = 86.66 (7)°]. The 4-nitro moiety is approximately coplanar with the benzene ring to which it is attached [O-N-C-C = 4.2 (2)°], whereas the one in the ortho position is twisted [O-N-C-C = 138.28 (13)°]. The mol-ecules associate via C-H⋯O inter-actions, involving both O atoms from the 2-nitro group, to form a helical supra-molecular chain along [010]. Nitro-nitro N⋯O inter-actions [2.8461 (19) Å] connect the chains into layers that stack along [001].

N-[(1,3-Benzodioxol-5-yl)meth-yl]benzene-sulfonamide: an analogue of capsaicin.

The title compound, C14H13NO4S, an analogue of capsaicin, differs from the latter by having a 1,3-benzodioxole ring rather than a 2-meth-oxy-phenol moiety, and having a benzene-sulfonamide group instead of an aliphatic amide chain. The five-membered ring is in an envelope conformation with the methyl-ene C atom lying 0.221 (6) Šout of the plane formed by the other four atoms. The dihedral angle between the phenyl ring and the mean plane of the 1,3-benzodioxole fused-ring system is 84.65 (4)°. In the crystal, mol-ecules aggregate into supra-molecular layers in the ac plane through C-H⋯O, N-H⋯O and C-H⋯π inter-actions.

N-[(1,3-Benzodioxol-5-yl)meth-yl]-4-methyl-benzamide: an analogue of capsaicin.

In the title compound, C16H15NO3, the five-membered 1,3-dioxole ring is in an envelope conformation with the methyl-ene C atom as the flap atom [lying 0.202 (3) Šout of the plane formed by the other four atoms]. The benzene ring makes a dihedral angle of 84.65 (4)° with the best least-squares plane through the 1,3-benzodioxole fused-ring system, which substitutes the 2-methoxyphenol moiety in capsaicin. In the crystal, mol-ecules are connected into a zigzag supra-molecular chain along the c-axis direction by N-H⋯O hydrogen bonds. These chains are connected into a layer in the ac plane by C-H⋯π inter-actions.

Preaustinoid A: a meroterpene produced by Penicillium sp.

THE TITLE MEROTERPENE PREAUSTINOID A (SYSTEMATIC NAME: methyl 15-hydr-oxy-2,6,6,10,13,15-hexa-methyl-17-methyl-ene-7,14,16-trioxotetra-cyclo-[11.3.1.0(2,11).0(5,10)]hepta-decane-1-car-box-yl-ate), C(26)H(36)O(6), features a fused four-ring arrangement. Three rings are in different distorted chair conformations and the other is in a distorted boat conformation. The absolute configuration was established based on [α(D)] = -4.97° (c = 1.10 g l(-1), CH(2)Cl(2)). In the crystal, the mol-ecules are connected into supra-molecular chains via O-H⋯O hydrogen bonds.

Neoaustin: a meroterpene produced by Penicillium sp.

The title meroterpene neoaustin {systematic name: (1'S,2'R,3S,7'R,9'S,11'S,12'R)-11'-hydr-oxy-2,2,2',9',12'-penta-methyl-6',15'-dimethyl-ene-2,6-dihydro-13'-oxaspiro-[pyran-3,5'-tetra-cyclo-[7.5.1.0(1,11).0(2,7)]penta-deca-ne]-6,10',14'-trione}, C(25)H(30)O(6), comprises five rings, three six-membered and two five-membered. The absolute configuration was established based on [α(D)] = +166.91° (c 1.21, CH(2)Cl(2)). In the crystal, the mol-ecules are connected into a supra-molecular helical chain via O-H⋯O hydrogen bonds reinforced by C-H⋯O contacts.

Crystal structure of 3-[2-(4-methyl-phen-yl)ethyn-yl]-2H-chromen-2-one.

The coumarin ring system in the title asymmetric alkyne, C18H12O2, is approximately planar (r.m.s. deviation of the 11 non-H atoms = 0.048 Å), and is inclined with respect to the methyl-benzene ring, forming a dihedral angle of 33.68 (4)°. In the crystal, supra-molecular zigzag chains along the c-axis direction are formed via weak C-H⋯O hydrogen bonds, and these are connected into double layers via weak C-H⋯π inter-actions; these stack along the a axis.

Crystal structure of 3-[2-(thio-phen-3-yl)ethyn-yl]-2H-chromen-2-one.

In the title compound, C15H8O2S, the coumarin moiety is approximately planar (r.m.s. deviation of the 11 non-H atoms = 0.025 Å) and is slightly inclined with respect to the plane of the thio-phen-3-yl ring, forming a dihedral angle of 11.75 (8)°. In the crystal, the three-dimensional architecture features a combination of coumarin-thio-phene C-H⋯π and π-π [inter-centroid distance = 3.6612 (12) Å] inter-actions.