Selective,C-3 Friedel-Crafts acylation to generate functionally diverse,acetylated Imidazo[1,2-a]pyridine derivatives

Carbon-carbon bonds are integral for pharmaceutical discovery and development. Frequently, CC bond reactions utilize expensive catalyst/ligand combinations and/or are low yielding, which can increase time and expenditures in pharmaceutical development. To enhance CC bond formation protocols, we developed a highly efficient, selective, and combinatorially applicable Friedel-Crafts acylation to acetylate the C-3 position of imidazo[1,2-a]pyridines. The reaction, catalyzed by aluminum chloride, is both cost effective and more combinatorial friendly compared to acetylation reactions requiring multiple, stoichiometric equivalents of AlCl₃. The protocol has broad application in the construction of acetylated imidazo[1,2-a]pyridines with an extensive substrate scope. All starting materials are common and the reaction requires inexpensive, conventional heating methods for adaptation in any laboratory. Further, the synthesized compounds are predicted to possess GABA activity through a validated, GABA binding model. The developed method serves as a superior route to generate C-3 acetylated imidazo[1,2-a]pyridine building-blocks for combinatorial synthetic efforts.     

Regio- and stereoselective co-iodination of olefins using NH4I and Oxone

A simple, efficient, and environmentally benign protocol for the synthesis of vicinal iodohydrins and iodoesters from olefins using NH₄I and Oxone in CH₃CN/H₂O (1:1) and dimethylformamide (DMF) / dimethylacetamide (DMA), respectively, without employing a catalyst at room temperature is described. Regio- and stereoselective iodohydroxylation and iodoesterification of various olefins with anti fashion, following Markonikov’s rule, was achieved and the corresponding products were obtained in good to excellent yields. In addition, 1,2-disubstituted olefins afforded excellent diastereoselectivity.     

Isolation and Crystal Structure of 6α,7α-Epoxy-5α,17α,27-trihydroxy-1-oxo-22R-witha-2,24-dienolide monohydrate-A Withasteroid from Withania somnifera Leaves

Abstract  

(5R,6S,7S,8S,9S,10R,13S,14S,17S,20R,22R)-6α,7α-epoxy-5α,17α,27-trihydroxy-1-oxo-22R-witha-2,24-dienolide has been isolated from Withania somnifera leaves. Three-dimensional X-ray intensity data were collected at 293 K on Bruker CCD area-detector diffractometer equipped with graphite-monochromated MoKα radiation (λ = 0.71073 ?). The compound crystallizes in monoclinic space group P21 with unit cell parameters: a = 6.4540(2), b = 11.3656(4), c = 17.4982(5) ?, β = 90.730 ^o(2), Z = 2. The crystal structure was refined to a final R-value of 0.0419 for 6122 observed reflections. One water solvent molecule was observed. All the rings of the steroid skeleton are trans connected. Rings A and B exists in a half-chair conformation, ring C a chair, and five membered ring D is intermediate between half-chair and envelope. The δ-lactone ring E adopts a distorted sofa conformation. The characteristic pattern observed in the packing diagram is the appearance of twisted chains of molecules. The packing of the molecules in the crystal is stabilized by intra- and intermolecular O–H···O and C–H···O interactions.     

Characterization of amino acid‐derived betaines by electrospray ionization tandem mass spectrometry

Betaines belong to the naturally occurring osmoprotectants or compatible solutes present in a variety of plants, animals and microorganisms. In recent years, metabolomic techniques have been emerging as a fundamental tool for biologists because the constellation of these molecules and their relative proportions provide with information about the actual biochemical condition of a biological system. Therefore, identification and characterization of biologically important betaines are crucial, especially for metabolomic studies. Most of the natural betaines are derived from amino acids and related homologues. Although, theoretically, all the amino acids can be converted to corresponding betaines by simple methylation of the amine group, only a few of the amino acid‐derived betaines were fully characterized in the literature. Here, we report a combined electrospray ionization tandem and high‐resolution mass spectrometry study of all the betaines derived from amino acids, including the isomeric betaines. The decomposition pathway of protonated, sodiated and potassiated molecule ions that enable unambiguous characterization of the betaines including the isomeric betaines and overlapping ionic species of different betaines is distinctive. Copyright © 2012 John Wiley & Sons, Ltd.     

On the equivalence of the Einstein–Hilbert and the Einstein–Palatini formulations of general relativity for an arbitrary connection

In the framework of the Einstein–Palatini formalism, even though the projective transformation connecting the arbitrary connection with the Levi-Civita connection has been floating in the literature for a long time and perhaps the result was implicitly known in the affine gravity community, yet as far as we know Julia and Silva were the first to realise its gauge character. We rederive this result by using the Rosenfeld–Dirac–Bergmann approach to constrained Hamiltonian systems and do a comprehensive self contained analysis establishing the equivalence of the Einstein–Palatini and the metric formulations without having to impose the gauge choice that the connection is symmetric. We also make contact with the the Einstein–Cartan theory when the matter Lagrangian has fermions.     

Vibrational spectroscopic investigation of poly(p‐phenylene sulfide)

Poly(p‐phenylene sulfide) (PPS) is an important polymer of engineering interest particularly useful in the electronics and automotive industries. Normal mode analysis including phonon dispersion has been performed to understand completely the vibrational spectra of this polymer. Various characteristic features of the dispersion curves have been reported. Crossing/Repulsion between various pairs of modes at certain phase values have been explained as arising due to internal symmetry in the energy momentum space. The heat capacity is calculated as a function of temperature via density‐of‐states in the range 220–360 K. © 2009 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 47: 2353–2367, 2009     

Weak Galerkin finite element methods combined with Crank-Nicolson scheme for parabolic interface problems

This article is devoted to the a priori error estimates of the fully discrete Crank-Nicolson approximation for the linear parabolic interface problem via weak Galerkin finite element methods (WG-FEM). All the finite element functions are discontinuous for which the usual gradient operator is implemented as distributions in properly defined spaces. Optimal order error estimates in both $L^{\infty}(H^1)$ and $L^{\infty}(L^2)$ norms are established for lowest order WG finite element space $({\cal P}_{k}(K),\;{\cal P}_{k-1}(\partial K),\;\big[{\cal P}_{k-1}(K)\big]^2)$. Finally, we give numerical examples to verify the theoretical results.     

Isothermal fluid sphere: Uniqueness and conformal mapping

We prove the theorem: A necessary and sufficient condition for a spacetime to represent an isothermal fluid sphere (linear equation of state with density falling off as inverse square of the curvature radius) without boundary is that it is conformal to a spacetime of zero gravitational mass (‘minimally’ curved).     

A Donsker-Varadhan type of invariance principle

Summary LetX ₁,X ₂,h. be i.i.d. random variables in the domain of attraction of a stable lawG, and denote S_n = X₁ + X_n, L_n(, A) =n_–1 satisfiesa(n) ^–1 S _n G. Large deviation probability estimates of Donsker-Varadhan type are obtained forL _n (, ·), and these are then used to study the behavior of small values of (S _n /a(n). These latter results are analogues of Strassen's results which described the behavior of large values of (S _n /a(n)) when the limit law was Gaussian. The limiting constants are seen to depend only on the limit lawG and not on the distribution ofX ₁. The techniques used are those developed by Donsker and Varadhan in their theory of large deviations.This work was partially supported by the National Science Foundation.