Stereocontrolled total synthesis of (+)-concanamycin F: the strategic use of boron-mediated aldol reactions of chiral ketones

A highly stereocontrolled total synthesis of the 18-membered macrolide (+)-concanamycin F, a potent inhibitor of vacuolar ATPases, is described that proceeds in 5.8% yield over 26 steps. The three key fragments, C1-C13 vinyl iodide, C14-C22 vinyl stannane and C23-C28 aldehyde, were efficiently constructed using asymmetric boron-mediated aldol reactions of appropriate chiral ketone building blocks. The nature of the silyl protection of the C7/C9 hydroxyls proved to be critical for achieving macrocyclisation, with TES ethers being superior to a cyclic silylene derivative. Following a Liebeskind-Stille cross-coupling reaction between the C1-C13 vinyl iodide and C14-C22 vinyl stannane fragments to assemble the (12E,14E)-diene, a modified Yamaguchi macrolactonisation delivered the requisite 18-membered macrocyclic core. This advanced intermediate was also obtained by an alternative sequence using an esterification step to connect the C1-C13 and C14-C22 fragments followed by a Pd-catalysed intramolecular Stille reaction to install the (12E,14E)-diene. Conversion of the resulting macrocyclic intermediate into a methyl ketone then enabled a highly diastereoselective Mukaiyama aldol coupling of the derived silyl enol ether with the C13-C28 aldehyde fragment to install the fully elaborated side chain, whereby subsequent global deprotection of the resulting β-hydroxyketone under suitable conditions (TASF followed by p-TsOH) afforded (+)-concanamycin F.     

Nature of the electronic states involved in the chemical bonding and superconductivity at high pressure in SnO

We have investigated the electronic structure and the Fermi surface of SnO using density functional theory calculations within recently proposed exchange-correlation potential (PBE + mBJ) at ambient conditions and high pressures up to 19.3 GPa where superconductivity was observed. It was found that the Sn valence states (5s, 5p, and 5d are strongly hybridized with the O 2p states, and that our density functional theory calculations are in good agreement with O K-edge X-ray spectroscopy measurements for both occupied and empty states. It was demonstrated that the metallic states appearing under pressure in the semiconducting gap stem due to the transformation of the weakly hybridized O 2p-Sn 5sp subband corresponding to the lowest valence state of Sn in SnO. We discuss the nature of the electronic states involved in chemical bonding and formation of the hole and electron pockets with nesting as a possible way to superconductivity.     

Rapid discovery of inhibitors of <Emphasis Type="Italic">Toxoplasma gondii</Emphasis> using hybrid structure-based computational approach

Toxoplasma (T.) gondii, the causative agent of toxoplasmosis, is a ubiquitous opportunistic pathogen that infects individuals worldwide, and is a leading cause of severe congenital neurologic and ocular disease in humans. No vaccine to protect humans is available, and hypersensitivity and toxicity limit the use of the few available medicines. Therefore, safer and more effective medicines to treat toxoplasmosis are urgently needed. Using the Hybrid Structure Based (HSB) method, we have previously identified small molecule inhibitors of P. falciparum that seem to target a novel protein–protein interaction between the Myosin tail interacting protein and myosin light chain. This pathway has been hypothesized to be involved in invasion of host erythrocytes by the parasite and is broadly conserved among the apicomplexans. Guided by similar computational drug design approaches, we investigated this series of small molecules as potential inhibitors of T. gondii. Compound C3-21, identified as the most active inhibitor in this series, exhibited an IC₅₀ value ~500 nM against T. gondii. Among the 16 structural analogs of C3-21 tested thus far, nine additional compounds were identified with IC₅₀ values <10.0 μM. In vitro assays have revealed that C3-21 markedly limits intracellular growth of T. gondii tachyzoites, but has no effect on host cell human foreskin fibroblasts (HFF) at concentrations more than a log greater than the concentration that inhibits the parasites.     

Acid Exfoliation of Imine-linked Covalent Organic Frameworks Enables Solution Processing into Crystalline Thin Films

Covalent organic frameworks (COFs) are highly modular porous crystalline polymers that are of interest for applications such as charge-storage devices, nanofiltration membranes, and optoelectronic devices. COFs are typically synthesized as microcrystalline powders, which limits their performance in these applications, and their limited solubility precludes large-scale processing into more useful morphologies and devices. We report a general, scalable method to exfoliate two-dimensional imine-linked COF powders by temporarily protonating their linkages. The resulting suspensions were cast into continuous crystalline COF films up to 10 cm in diameter, with thicknesses ranging from 50 nm to 20 μm depending on the suspension composition, concentration, and casting protocol. Furthermore, we demonstrate that the film fabrication process proceeds through a partial depolymerization/repolymerization mechanism, providing mechanically robust films that can be easily separated from their substrates.     

Smooth static solutions of the Einstein/Yang-Mills equations

We consider the Einstein/Yang-Mills equations in 3+1 space time dimensions withSU(2) gauge group and prove rigorously the existence of a globally defined smooth static solution. We show that the associated Einstein metric is asymptotically flat and the total mass is finite. Thus, for non-abelian gauge fields the Yang-Mills repulsive force can balance the gravitational attractive force and prevent the formation of singularities in spacetime.Research supported in part by the NSF, Contract No. DMS 89-05205Research supported in part by the ONR, Contract No. DOD-C-N-00014-88-K-0082Research supported in part by the DOE, Grant No. DE-FG02-88ER25065Research supported in part by the U.K. Science and Engineering Research Council     

Ratios of charged antiparticles-to-particles near mid-rapidity in Au + Au collisions at sqrt[s(NN)]=130 GeV

We have measured the ratios of antiparticles to particles for charged pions, kaons, and protons near mid-rapidity in central Au+Au collisions at sqrt[s(NN)] = 130 GeV. We observe / = 1.00+/-0.01(stat)+/-0.02(syst), / = 0.91+/-0.07(stat)+/-0.06(syst), and

/

= 0.60+/-0.04(stat)+/-0.06(syst). The / and

/

ratios give a consistent estimate of the baryo-chemical potential mu(B) of 45 MeV, a factor of 5-6 smaller than in central Pb+Pb collisions at sqrt[s(NN)] = 17.2 GeV.     

A connection formula for the second Painlevé transcendent

We consider the second Painlevé transcendent $$\frac{{d^2 y}}{{dx^2 }} = xy + 2y^3 .$$ It is known that if y(x) ～ k Ai (x) as x → + ∞, where ?1<k<1 and Ai (x) denotes Airy's function, then $$y(x) \sim d|x|^{ - \tfrac{1}{4}} sin\{ \tfrac{2}{3}|x|^{\tfrac{3}{2}} - \tfrac{3}{4}d^2 1n|x| - c\} ,$$ where the constants d, c depend on k. This paper shows that $$d^2 = \pi ^{ - 1} 1n(1 - k^2 )$$ , which confirms a conjecture by Ablowitz & Segur.     

On the flow between two counter-rotating infinite plane disks

This paper studies the boundary-value problem arising from the behaviour of a fluid occupying the region -1≦x≦1 between two rotating disks, rotating about a common axis perpendicular to their planes when the disks are rotating with the same speed Ω₀ but in the opposite sense. The equations which describe the axially symmetric similarity solutions of this problem are $$\varepsilon H^{iv} + HH''' + GG' = 0$$ $$\varepsilon G'' + HG' - H'G = 0$$ with the boundary conditions $$H( \pm 1) = H'( \pm 1) = 0$$ $$G( - 1) = - 1,{\text{ }}G(1) = 1$$ where ?=v/2Ω₀ and v is the kinematic viscosity. The existence of an odd solution is established. This particular solution satisfies many special conditions, for example, G′ (x, ?)>0. Moreover, precise estimates are obtained on the size and behaviour of the solution as ? ↓ 0.