Ruthenium hydride catalyzed silylvinylation of terminal alkynes under ethylene atmosphere at 80 psi

The development of methods for the stereoselective synthesis of polysubstituted 1,3-dienes is a challenge to synthetic chemistry. Herein is reported a selective approach for the synthesis of polysubstituted 1,3-dienes using the ruthenium hydride catalyzed intramolecular silylvinylation of alkynes under 80 psi of ethylene gas. This strategy affords a single diene isomer, is applicable to substrates with aryl and alkyl substitution at the propargyl and homopropargyl positions, and has been utilized in the synthesis of 5- and 6-membered oxasilacycles.     

Serendipitous discovery of light-induced (<Emphasis Type="Italic">In Situ</Emphasis>) formation of an Azo-bridged dimeric sulfonated naphthol as a potent PTP1B inhibitor

Background

Protein tyrosine phosphatases (PTPs) like dual specificity phosphatase 5 (DUSP5) and protein tyrosine phosphatase 1B (PTP1B) are drug targets for diseases that include cancer, diabetes, and vascular disorders such as hemangiomas. The PTPs are also known to be notoriously difficult targets for designing inihibitors that become viable drug leads. Therefore, the pipeline for approved drugs in this class is minimal. Furthermore, drug screening for targets like PTPs often produce false positive and false negative results.

Results

Studies presented herein provide important insights into: (a) how to detect such artifacts, (b) the importance of compound re-synthesis and verification, and (c) how in situ chemical reactivity of compounds, when diagnosed and characterized, can actually lead to serendipitous discovery of valuable new lead molecules. Initial docking of compounds from the National Cancer Institute (NCI), followed by experimental testing in enzyme inhibition assays, identified an inhibitor of DUSP5. Subsequent control experiments revealed that this compound demonstrated time-dependent inhibition, and also a time-dependent change in color of the inhibitor that correlated with potency of inhibition. In addition, the compound activity varied depending on vendor source. We hypothesized, and then confirmed by synthesis of the compound, that the actual inhibitor of DUSP5 was a dimeric form of the original inhibitor compound, formed upon exposure to light and oxygen. This compound has an IC₅₀ of 36 μM for DUSP5, and is a competitive inhibitor. Testing against PTP1B, for selectivity, demonstrated the dimeric compound was actually a more potent inhibitor of PTP1B, with an IC₅₀ of 2.1 μM. The compound, an azo-bridged dimer of sulfonated naphthol rings, resembles previously reported PTP inhibitors, but with 18-fold selectivity for PTP1B versus DUSP5.

Conclusion

We report the identification of a potent PTP1B inhibitor that was initially identified in a screen for DUSP5, implying common mechanism of inhibitory action for these scaffolds.

     

High asymmetric induction in diels-alder additions of cyclopentadiene to acrylates derived from isoborneol

Starting from (R)-(+)- and from (S)-(?)-camphor the chiral alcohols $\text{1}$, $\text{2}$ and $\text{3}$ have been prepared; their acrylates II underwent TiCl₂(OR)₂-promoted Diels-Alder additions to cyclopentadiene giving efficiently in a predictable manner either the (2R)- or the (2S)-adducts III with up to virtually quantitative asymmetric induction.     

The separation of palladium and platinum by ion flotation

Differences in the ion flotation properties of palladium(II) and platinum(IV) chloro complexes in aqueous solutions are used to achieve separations of these metals. The anionic chloro complex PtCl^2-₆ is floated selectively with cationic surfactants of the type, RNR'₃Br, from solutions of PdCl^2-₄ and various concentrations of hydrochloric acid. The palladium(II) does not float from solutions of ? 3.0 M HCl and the platinum(IV) floated from these solutions can be recovered free of palladium. However, the separation is incomplete as much of the platinum(IV) is also unfloated from these solutions. Quantitative separations are obtained by conversion of the palladium(II) to the cationic ammine, Pd(NH₃)₄²⁺ with aqueous ammonia prior to flotation. The anionic chloro complex of platinum(IV) is unaffected by the presence of ammonia and is floated quantitatively with the surfactant n-hexadecyltri-n-propylammonium bromide from 0.01 M ammonia solutions.     

Fenchel Duality Theory and a Primal-Dual Algorithm on Riemannian Manifolds

Foundations of Computational Mathematics - This paper introduces a new notion of a Fenchel conjugate, which generalizes the classical Fenchel conjugation to functions defined on Riemannian...     

Avoidance of split overlaps

We generalize Axel Thue’s familiar definition of overlaps in words, and observe that there are no infinite words avoiding split occurrences of these generalized overlaps. We give estimates for the length of the longest finite word that avoids split overlaps. Along the way we prove a useful theorem about repeated disjoint occurrences in words — an interesting natural variation on the classical de Bruijn sequences.     

Eigenvalues Estimate for the Neumann Problem of a Bounded Domain

In this note, we investigate upper bounds of the Neumann eigenvalue problem for the Laplacian of a domain Ω in a given complete (not compact a priori) Riemannian manifold (M,g). For this, we use test functions for the Rayleigh quotient subordinated to a family of open sets constructed in a general metric way, interesting for itself. As applications, we prove that if the Ricci curvature of (M,g) is bounded below Ric  ^g ≥−(n−1)a ², a≥0, then there exist constants A _n >0,B _n >0 only depending on the dimension, such that

Which distance-hereditary graphs are cover–incomparability graphs?

In this paper we deal with cover–incomparability graphs of posets, or briefly C–I graphs. These are graphs derived from posets as the edge-union of their cover graph and their incomparability graph. We answer two recently posed open questions. Which distance-hereditary graphs are C–I graphs? Which Ptolemaic (i.e. chordal distance-hereditary) graphs are C–I graphs? It follows that C–I graphs can be recognized efficiently in the class of all distance-hereditary graph whereas recognizing C–I graphs in general is known to be NP-complete.     

Sensitivity analysis of composite piecewise smooth equations

This paper is a contribution to the sensitivity analysis of piecewise smooth equations. A piecewise smooth function is a Lipschitzian homeomorphism near a given point if and only if it is coherently oriented and has an invertible B-derivative at this point. We emphasise the role of functions of the typef=g °h whereg is piecewise smooth andh is smooth and present verifiable conditions which ensure that the functionf=g ° is a Lipschitzian homeomorphism near a given point for every sufficiently close toh with respect to theC ¹-topology. Revised version of part of the paper “Sensitivity analysis and Newton’s method for composite piecewise smooth equations”.