Mild AgOTf Catalyzed Synthesis of 1-Carbosubstituted-isochromenes

One of the most efficient methods for the construction of 1-substituted isochromenes (and related heteroaryl compounds such as pyrano[4,3-b]pyridines) is the metal catalyzed regioselective domino cycloisomerization/nucleophilic addition reaction of a properly substituted 2-alkynyl(hetero)arylaldehyde in the presence of a suitable nucleophile. The reaction with oxygen nucleophiles is the most studied and several metal catalyst, i.e., Pd(II), Cu(I), Ag(I), Au(I) and In(III), demonstrated to be effective for synthesis of 1-alkoxyisochromenes. Conversely, the reaction with carbon nucleophiles, and in particular with enolizable carbonyl compounds, is relatively less investigated. In connection with our ongoing interest in the development of silver catalysed domino approaches involving alkyne derivatives, we report here a silver catalyzed domino approach to isochromenes starting from 2-alkynyl(hetero)arylaldehydes and enolizable carbonyl compounds. The reaction yields range from fair to very good. The reaction mechanism is also investigated and the formation of by-products discussed

Gold-Catalyzed Cascade Reactions of 4H-Furo[3,2-b]indoles with Allenamides: Synthesis of Indolin-3-one Derivatives

Merging the ability of cationic gold(I) catalysts to activate unsaturated \u3c0-systems with the electrophiles driven ring-opening reactions of furans, we describe a new approach to 2-spiroindolin-3-ones from 4H-furo[3,2-b]indoles. The reaction occurs through a cascade sequence involving addition of a gold-activated allene to the furan moiety of the starting furoindole followed by a ring-opening/ring-closing event affording 2-spirocyclopentane-1,2-dihydro-3H-indolin-3-ones in moderate to good yields

T-LAK cell-originated protein kinase (TOPK): an emerging target for cancer-specific therapeutics

‘Targeted’ or ‘biological’ cancer treatments rely on differential gene expression between normal tissue and cancer, and genetic changes that render tumour cells especially sensitive to the agent being applied. Problems exist with the application of many agents as a result of damage to local tissues, tumour evolution and treatment resistance, or through systemic toxicity. Hence, there is a therapeutic need to uncover specific clinical targets which enhance the efficacy of cancer treatment whilst minimising the risk to healthy tissues. T-LAK cell-originated protein kinase (TOPK) is a MAPKK-like kinase which plays a role in cell cycle regulation and mitotic progression. As a consequence, TOPK expression is minimal in differentiated cells, although its overexpression is a pathophysiological feature of many tumours. Hence, TOPK has garnered interest as a cancer-specific biomarker and biochemical target with the potential to enhance cancer therapy whilst causing minimal harm to normal tissues. Small molecule inhibitors of TOPK have produced encouraging results as a stand-alone treatment in vitro and in vivo, and are expected to advance into clinical trials in the near future. In this review, we present the current literature pertaining to TOPK as a potential clinical target and describe the progress made in uncovering its role in tumour development. Firstly, we describe the functional role of TOPK as a pro-oncogenic kinase, followed by a discussion of its potential as a target for the treatment of cancers with high-TOPK expression. Next, we provide an overview of the current preclinical progress in TOPK inhibitor discovery and development, with respect to future adaptation for clinical use

The structure of epitaxial V2O3 films and their surfaces : a medium energy ion scattering study

Medium energy ion scattering, using 100 keV H+ incident ions, has been used to investigate the growth of epitaxial films, up to thicknesses of ~200 Å, of V2O3 on both Pd(111) and Au(111). Scattered-ion energy spectra provide a measure of the average film thickness and the variations in this thickness, and show that, with suitable annealing, the crystalline quality is good. Plots of the scattering yield as a function of scattering angle, so-called blocking curves, have been measured for two different incidence directions and have been used to determine the surface structure. Specifically, scattering simulations for a range of different model structures show poor agreement with experiment for half-metal (….V’O3V) and vanadyl (….V’O3V=O) terminations, with and without surface interlayer relaxations. However, good agreement with experiment is found for the modified oxygen-termination structure, first proposed by Kresse et al., in which a subsurface V half-metal layer is moved up into the outermost V buckled metal layer to produce a VO2 overlayer on the underlying V2O3, with an associated layer structure of ….O3VV’’V’O3

Stability of sub-surface oxygen at Rh(111)

Using density-functional theory (DFT) we investigate the incorporation of oxygen directly below the Rh(111) surface. We show that oxygen incorporation will only commence after nearly completion of a dense O adlayer (\theta_tot = 1.0 monolayer) with O in the fcc on-surface sites. The experimentally suggested octahedral sub-surface site occupancy, inducing a site-switch of the on-surface species from fcc to hcp sites, is indeed found to be a rather low energy structure. Our results indicate that at even higher coverages oxygen incorporation is followed by oxygen agglomeration in two-dimensional sub-surface islands directly below the first metal layer. Inside these islands, the metastable hcp/octahedral (on-surface/sub-surface) site combination will undergo a barrierless displacement, introducing a stacking fault of the first metal layer with respect to the underlying substrate and leading to a stable fcc/tetrahedral site occupation. We suggest that these elementary steps, namely, oxygen incorporation, aggregation into sub-surface islands and destabilization of the metal surface may be more general and precede the formation of a surface oxide at close-packed late transition metal surfaces.Comment: 9 pages including 9 figure files. Submitted to Phys. Rev. B. Related publications can be found at http://www.fhi-berlin.mpg.de/th/paper.htm

Metastable precursors during the oxidation of the Ru(0001) surface

Using density-functional theory, we predict that the oxidation of the Ru(0001) surface proceeds via the accumulation of sub-surface oxygen in two-dimensional islands between the first and second substrate layer. This leads locally to a decoupling of an O-Ru-O trilayer from the underlying metal. Continued oxidation results in the formation and stacking of more of these trilayers, which unfold into the RuO_2(110) rutile structure once a critical film thickness is exceeded. Along this oxidation pathway, we identify various metastable configurations. These are found to be rather close in energy, indicating a likely lively dynamics between them at elevated temperatures, which will affect the surface chemical and mechanical properties of the material.Comment: 11 pages including 9 figures. Submitted to Phys. Rev. B. Related publications can be found at http://www.fhi-berlin.mpg.de/th/paper.htm

Winter roost occupancy and behaviour at evening departure of urban long‐eared owls

Roost occupancy and behaviour at evening departure were studied in long-eased owls (Asio otus) at a large winter roost in the southern suburbs of the city of Milan, northern Italy. The number of roosting owls was strongly correlated with decreasing daylength, while it was weakly negatively correlated with temperature. Hence changes in photoperiod can be considered among the proximate factors promoting the winter aggregation of long-eared owls. Behaviour at departure was influenced by cloud cover: birds departed earlier, and departures were at a higher altitude and less concentrated, with covered sky than with clear sky; the reasons for these behavioural differences remain unclear. Directions of departure showed that owls do not use the urban area for hunting, as no birds were observed flying towards the city, consistently with dietary data