Synthesis of (-)-amphidinolide K fragment C9-C22

[reaction: see text] The key fragment (2a or 2b) in a total synthesis of the cytotoxic macrolide (-)-amphidinolide K (1) has been achieved from synthons C9-C14 (3) and C15-C22 (4), which have both been prepared from glutamic acid in good overall yields.     

Potent small-molecule binding to a dynamic hot spot on IL-2

The complexes between IL-2 and two similar small molecules, one a lead compound and the other a potent, affinity-optimized compound, were determined by X-ray crystallography. The lead compound (IC50 = 6 muM) bound to a hot spot on IL-2 in a groove that is not apparent in either the unliganded protein or a complex between IL-2 and a weakly bound drug fragment. The affinity-optimized compound (IC50 = 0.06 muM), which has an added aromatic acid fragment, bound in the same groove as the lead compound. In addition, a novel binding site was formed for the aromatic acid which is unseen in the complex with the lead compound. Thus, the hot spot on IL-2 is highly dynamic, with the protein changing form at multiple sites to maximize packing for each compound. Binding-site rigidity is often thought to play a role in high-affinity interactions. However, in this case, specific contacts between the small molecule and the protein are made despite the adaptivity of the hot spot. Given the change in morphology that was observed in IL-2, it is unlikely that a potent inhibitor could have been found by rational design. Therefore, fragment assembly methods offer the stochastic advantage of finding fragments in flexible protein regions where structural changes are unpredictable.     

Asymptotic dimension of finitely presented groups

We prove that if a finitely presented group is one-ended, then its asymptotic dimension is greater than . It follows that a finitely presented group of asymptotic dimension is virtually free.

     

A game semantics for disjunctive logic programming

Denotational semantics of logic programming and its extensions (by allowing negation, disjunctions, or both) have been studied thoroughly for many years. In 1998, a game semantics was given to definite logic programs by Di Cosmo, Loddo, and Nicolet, and a few years later it was extended to deal with negation by Rondogiannis and Wadge. Both approaches were proven equivalent to the traditional semantics. In this paper we define a game semantics for disjunctive logic programs and prove soundness and completeness with respect to the minimal model semantics of Minker. The overall development has been influenced by the games studied for PCF and functional programming in general, in the styles of Abramsky–Jagadeesan–Malacaria and Hyland–Ong–Nickau.     

Reaction of Dess-Martin periodinane with 2-(alkylselenyl)pyridines. Dehydration of primary alcohols under extraordinarily mild conditions

Dess-Martin periodinane oxidizes very rapidly 2-pyridylseleno derivatives RR′CHCH₂SePy in CHCl₃ or CH₂Cl₂ and more chemoselectively than mCPBA. Tetravalent selenanes, RR′CHCH₂Se(OAc)₂Py, seem to be formed. Treatment of these intermediates with aqueous NaHCO₃ gives rise to irreversible hydrolysis and elimination to terminal alkenes. As the OH/SePy exchange can be performed in minutes, the overall process is an exceptionally efficient procedure for the dehydration of primary alcohols.     

Crystallization and surface morphology of Au/SiO2 thin films following furnace and flame annealing

A crystallization and surface evolution study of Au thin film on SiO₂ substrates following annealing at different temperatures above the eutectic point of the Au/Si system are reported. Samples were prepared by conventional evaporation of gold in a high vacuum (10⁻⁷ mbar) environment on substrates at room temperature. Thermal treatments were performed by both furnace and flame annealing techniques. Au thin films can be crystallized on SiO₂ substrates by both furnace and flame annealing. Annealing arranges the Au crystallites in the (1 1 1) plane direction and changes the morphology of the surface. Both, slow and rapid annealing result in a good background in the XRD spectra and hence clean and complete crystallization which depends more on the temperature than on the time of annealing. The epitaxial temperature for the Au/SiO₂ system decreases in the range of 350-400 °C. Furnace and flame annealing also form crystallized gold islands over the Au/SiO₂ surface. Relaxation at high temperatures of the strained Au layer, obtained after deposition, should be responsible for the initial stages of clusters formation. Gold nucleation sites may be formed at disordered points on the surface and they become islands when the temperature and time of annealing are increased. The growth rate of crystallites is highest around 360 °C. Above this temperature, the layer melts and gold diffuses from the substrate to the nucleation sites to increase the distance between islands and modify their shapes. Well above the eutectic temperature, the relaxed islands have hexagonally shaped borders. The mean crystallite diameters grow up to a maximum mean size of around 90 nm. The free activation energy for grain boundary migration above 360 °C is 0.2 eV. Therefore the type of the silicon substrate changes the mechanism of diffusion and growth of crystallites during annealing of the Au/Si system. Epitaxial Au(1 1 1) layers without formation of islands can be prepared by furnace annealing in the range of 300-310 °C and by flame annealing of a few seconds and up to 0.5 min.     

A new scalable synthesis of entecavir

A new synthesis of entecavir from d-glucose in an average total yield of 3.5% was achieved via an intramolecular nitrile oxide cycloaddition (INOC) reaction and a Peterson olefination as key-steps. The present process was designed for industrial application, using widely available raw materials, simple and cheap reagents and avoiding low reaction temperatures, which are very common in the synthetic approaches towards similarly complex structures.