Stereoselective Synthesis and Antiproliferative Activity of Steviol-Based Diterpene 1,3-Aminoalcohol Regioisomers

A series of novel diterpene-type 1,3-aminoalcohols and their regioisomers have been synthesised from natural stevioside in a stereoselective manner. The key intermediate β-keto alcohol was prepared using Wagner–Meerwein rearrangement of the epoxide derived from steviol methyl ester. The primary aminoalcohol was formed via Raney-nickel-catalysed hydrogenation of an oxime, and a versatile library of aminoalcohols was synthesised using a Schiff base with the primary amines. The aminoalcohol regioisomers were prepared from the mesylate of the β-keto alcohols. The corresponding primary aminoalcohol was formed via the palladium-catalysed hydrogenation of hydroxyl-azide, and click reactions of the latter were also carried out. The new compounds were characterised using 1D- and 2D-NMR techniques and HRMS measurements. The in vitro investigations showed high inhibition of cell growth in human cancer cell lines (HeLa, SiHa, A2780, MCF-7 and MDA-MB-231) in the case of naphthalic N-substituted derivatives. The antiproliferative effects were assayed using the MTT method

On the brink of change: plant responses to climate on the Colorado Plateau

The intensification of aridity due to anthropogenic climate change in the southwestern U.S. is likely to have a large impact on the growth and survival of plant species that may already be vulnerable to water stress. To make accurate predictions of plant responses to climate change, it is essential to determine the long-term dynamics of plant species associated with past climate conditions. Here we show how the plant species and functional types across a wide range of environmental conditions in Colorado Plateau national parks have changed with climate variability over the last twenty years. During this time, regional mean annual temperature increased by 0.188C per year from 1989–1995, 0.068C per year from 1995–2003, declined by 0.148C from 2003–2008, and there was high interannual variability in precipitation. Non-metric multidimensional scaling of plant species at long-term monitoring sites indicated five distinct plant communities. In many of the communities, canopy cover of perennial plants was sensitive to mean annual temperature occurring in the previous year, whereas canopy cover of annual plants responded to cool season precipitation. In the perennial grasslands, there was an overall decline of C3 perennial grasses, no change of C4 perennial grasses, and an increase of shrubs with increasing temperature. In the shrublands, shrubs generally showed no change or slightly increased with increasing temperature. However, certain shrub species declined where soil and physical characteristics of a site limited water availability. In the higher elevation woodlands, Juniperus osteosperma and shrub canopy cover increased with increasing temperature, while Pinus edulis at the highest elevation sites was unresponsive to interannual temperature variability. These results from well-protected national parks highlight the importance of temperature to plant responses in a water-limited region and suggest that projected increases in aridity are likely to promote grass loss and shrub expansion on the Colorado Plateau

Stereoselective Synthesis and Application of Gibberellic Acid-Derived Aminodiols

A series of gibberellic acid-based aminodiols was designed and synthesized from commercially available gibberellic acid. Exposure of gibberellic acid to hydrochloric acid under reflux conditions resulted in aromatization followed by rearrangement to form allo-gibberic acid. The key intermediate, ethyl allo-gibberate, was prepared according to literature methods. Epoxidation of key intermediate and subsequent ring-opening of the corresponding epoxide with different nucleophiles resulted in N-substituted aminodiols. The regioselective ring closure of N-benzyl-substituted aminodiol with formaldehyde was also investigated. All aminodiol derivatives were well characterized using modern spectroscopic techniques and evaluated for their antiproliferative activity against a panel of human cancer cell lines. In addition, structure–activity relationships were examined by assessing substituent effects on the aminodiol systems. The results indicated that aminodiols containing aromatic rings on their nitrogen substituents displayed significant cytotoxic effects. Among these agents, N-naphthylmethyl-substituted aminodiols were found to be the most potent candidates in this series. One of these molecules exhibited a modest cancer selectivity determined by non-cancerous fibroblast cells. A docking study was also made to exploit the observed results

4-Anilino-3-nitro-N-phenyl­benzamide

In the title compound, C19H15N3O3, the anilino and benzamide rings make dihedral angles of 10.66 (16) and 50.39 (16)°, respectively, with the nitro-substituted benzene ring. The nitro group is slightly twisted by 11.49 (17)° with respect to the attached benzene ring. There is an intra­molecular N—H⋯O hydrogen bond forming an S(6) ring. In the crystal, weak inter­molecular N—H⋯O and C—H⋯O hydrogen bonds link the mol­ecules into a chain parallel to the b axis. Futhermore, weak slipped π–π inter­actions [centroid–centroid distance = 3.819 (2) Å, inter­planar distance = 3.567 Å and offset angle [how is the offset angle defined?] = 21°] between the anilino ring and its symmetry-related counterpart may help to stabilize the packing

4-Anilino-3-nitro­benzonitrile

In the title compound, C13H9N3O2, the aromatic rings are twisted with respect to each other, making a dihedral angle of 49.41 (9)°. The nitro group and the nitrile group are nearly in the plane of the benzonitrile ring, the largest deviation from the plane being 0.123 (1) Å. There is an intra­molecular N—H⋯O hydrogen bond forming an S(6) ring. Weak inter­molecular C—H⋯O hydrogen bonds link the mol­ecules into a chain parallel to the c axis. Futhermore, slipped π–π inter­actions between symmetry-related phenyl rings [centroid–centroid distance 3.808 (1) Å, inter­planar distance 3.544 (8) Å with an offset of 21.5°] stabilize the structure