Tungsten-anisole complex provides 3,6-substituted cyclohexenes for highly diversified chemical libraries.

Medicinal chemists use vast combinatorial molecular libraries to develop leads for new pharmaceuticals. The syntheses of these compounds typically rely on coupling molecular fragments through atoms with planar (sp) geometry. These so-called flat molecules often lack the protein binding site specificity needed to be an effective drug.

The double protonation of dihapto-coordinated benzene complexes enables dearomatization using aromatic nucleophiles.

Friedel-Crafts Arylation (the Scholl reaction) is the coupling of two aromatic rings with the aid of a strong Lewis or Brønsted acid. This historically significant C-C bond forming reaction normally leads to aromatic products, often as oligomeric mixtures, dictated by the large stabilization gained upon their rearomatization. The coordination of benzene by a tungsten complex disrupts the natural course of this reaction sequence, allowing for Friedel-Crafts Arylation without rearomatization or oligomerization.

The eIF4EBP-eIF4E axis regulates CD4 T cell differentiation through modulation of T cell activation and metabolism.

CD4 T cells are critical for adaptive immunity, differentiating into distinct effector and regulatory subsets. Although the transcriptional programs underlying their differentiation are known, recent research has highlighted the importance of mRNA translation in determining protein abundance. We previously conducted genome-wide analysis of translation in CD4 T cells revealing distinct translational signatures distinguishing these subsets, identifying eIF4E as a central differentially translated transcript.

Coordination of Electron-Deficient Arenes with Group 6 Dearomatization Agents.

The exceptionally -basic metal fragments {MoTp-(NO)(DMAP)} and {WTp(NO)(PMe)} (Tp = tris(pyrazolyl)borate; DMAP = 4-(,-dimethylamino)pyridine) form thermally stable -coordinated complexes with a variety of electron-deficient arenes. The tolerance of substituted arenes with fluorine-containing electron withdrawing groups (EWG; -F, -CF, -SF) is examined for both the molybdenum and tungsten systems. When the EWG contains a bond (nitriles, aldehydes, ketones, ester), coordination occurs predominantly on the nonaromatic functional group.

Experiments and Direct Dynamics Simulations That Probe η-Arene/Aryl Hydride Equilibria of Tungsten Benzene Complexes.

Key steps in the functionalization of an unactivated arene often involve its dihaptocoordination by a transition metal followed by insertion into the C-H bond. However, rarely are the η-arene and aryl hydride species in measurable equilibrium. In this study, the benzene/phenyl hydride equilibrium is explored for the {WTp(NO)(PBu)} (Bu = -butyl; Tp = trispyrazoylborate) system as a function of temperature, solvent, ancillary ligand, and arene substituent.

Teratoid Hepatoblastoma With Yolk Sac-Like and Neuroendocrine Elements.

Teratoid hepatoblastoma (HB) is a variant of mixed HB described as having a mixture of heterologous components. A 3-year-old boy presented for a liver transplant evaluation due to persistent HB. His liver was biopsied as well as a perirenal mass.

Molybdenum-Promoted Synthesis of Isoquinuclidines with Bridgehead CF Groups.

The preparation of the complex MoTp(NO)(DMAP)(4,5-η-(2-trifluoromethyl)pyridine) (DMAP = 4-(dimethylamino)pyridine; Tp = tris(pyrazolyl)borate) is described. The CF substituent is found to preclude κ-N coordination, allowing for direct coordination without protection of the nitrogen. The dihapto-coordinate complex can be isolated as a single diastereomer, methylated, and reacted with a range of nucleophiles.

Highly Functionalized Cyclohexenes Derived from Benzene: Sequential Tandem Addition Reactions Promoted by Tungsten.

The dihapto-coordination of benzene to the π-basic fragment {TpW(NO)(PMe)} (Tp = hydridotris(pyrazolyl)-borate) enhances the basicity of the arene ligand to the point that it can be protonated with a mild Brønsted acid (diphenylammonium triflate; p K ∼ 1). The resulting η-benzenium complex reacts with a wide range of nucleophiles including protected enolates, cyanide, amines, methoxide, and aromatic nucleophiles to form 5-substituted 3,4-η-1,3-cyclohexadiene complexes in good yield (42-70%). These coordinated dienes were successfully taken through a second protonation and nucleophilic addition with a similar scope of nucleophiles (54-80%).

Molybdenum(0) Dihapto-Coordination of Benzene and Trifluorotoluene: The Stabilizing and Chemo-Directing Influence of a CF Group.

The preparation of the complexes TpMo(NO)(DMAP)(η-PhCF) (5) and TpMo(NO)(DMAP)(η-benzene) (3) is described. The CF group is found to stabilize the metal-arene bond strength in 5 by roughly 3 kcal/mol compared to that in 3, allowing the large-scale synthesis and isolation of the trifluorotoluene analogue (5, 37 g, 70%). When a benzene solution of 5 is allowed to stand, clean conversion to the benzene analogue 3 occurs, and this complex may be precipitated from solution upon the addition of pentane and isolated.

Intranasal immunization with influenza antigens conjugated with cholera toxin subunit B stimulates broad spectrum immunity against influenza viruses.

Frequent mutation of influenza viruses keep vaccinated and non-vaccinated populations vulnerable to new infections, causing serious burdens to public health and the economy. Vaccination with universal influenza vaccines would be the best way to effectively protect people from infection caused by mismatched or unforeseen influenza viruses. Presently, there is no FDA approved universal influenza vaccine.