Halide Anion Triggered Reactions of Michael Acceptors with Tropylium Ion

Tropylium bromide undergoes noncatalyzed, regioselective additions to a large variety of Michael acceptors. In this way, acrylic esters are converted into β‐bromo‐α‐cycloheptatrienylpropionic esters. The reactions are interpreted as nucleophilic attack of bromide ions at the electron‐deficient olefins and the approach of the tropylium ion to the incipient carbanion. Quantum chemical calculations were performed to elucidate the analogy to the amine‐ or phosphine‐catalyzed Rauhut–Currier reactions. Subsequent synthetic transformations of the bromo‐cycloheptatrienylated adducts are reported.     

Nickel‐Catalyzed 1,2‐Diarylation of Alkenyl Carboxylates: A Gateway to 1,2,3‐Trifunctionalized Building Blocks

A nickel‐catalyzed conjunctive cross‐coupling of alkenyl carboxylic acids, aryl iodides, and aryl/alkenyl boronic esters is reported. The reaction delivers the desired 1,2‐diarylated and 1,2‐arylalkenylated products with excellent regiocontrol. To demonstrate the synthetic utility of the method, a representative product is prepared on gram scale and then diversified to eight 1,2,3‐trifunctionalized building blocks using two‐electron and one‐electron logic. Using this method, three routes toward bioactive molecules are improved in terms of yield and/or step count. This method represents the first example of catalytic 1,2‐diarylation of an alkene directed by a native carboxylate group.     

Ni(COD)(DQ): An Air‐Stable 18‐Electron Nickel(0)–Olefin Precatalyst

We report that Ni(COD)(DQ) (COD=1,5‐cyclooctadiene, DQ=duroquinone), an air‐stable 18‐electron complex originally described by Schrauzer in 1962, is a competent precatalyst for a variety of nickel‐catalyzed synthetic methods from the literature. Due to its apparent stability, use of Ni(COD)(DQ) as a precatalyst allows reactions to be conveniently performed without use of an inert‐atmosphere glovebox, as demonstrated across several case studies.     

Acylated flavonoid glycosides from Barringtonia racemosa

Abstract

Using various chromatographic separations, three new acylated flavonoid glycosides, namely barringosides G–I (1–3), were isolated from the water-soluble extract of Barringtonia racemosa branches and leaves. The structure elucidation was performed by extensive analysis of the 1D and 2D NMR and HR-QTOF-MS data. Of the isolated compounds, barringoside I (3) showed moderate inhibitory effects on LPS-induced NO production in RAW264.7 cells with an IC₅₀ of 52.48?±?1.04?µM.     

Triterpene glycosides from the Vietnamese sea cucumber Holothuria edulis

Abstract

From the MeOH extract of the Vietnamese sea cucumber Holothuria edulis, eight triterpene glycosides (1–8), including one new compound namely holothurin A₅ (1), were isolated by using various chromatographic separations. Their structures were established by spectroscopic experiments including 1D, 2D NMR and HR-ESI-MS. Holothurin A₅ (1) has a hydroperoxy group at C-25. To the best of our knowledge, this is the first report of this group in triterpene saponins obtained from sea cucumbers to date. In addition, the in vitro cytotoxicity against five human cancer cell lines (HepG2, KB, LNCaP, MCF7 and SK-Mel2) of all isolated compounds was also evaluated using SRB assays.     

Data assimilation and pollution forecasting in Burgers' equation with model error function

This article presents a correction method for a better resolution of the problem of estimating and predicting pollution, governed by Burgers' equations. The originality of the method consists in the introduction of an error function into the system's equations of state to model uncertainty in the model. The initial conditions and diffusion coefficients, present in the equations for pollution and concentration, and also those in the model error equations, are estimated by solving a data assimilation problem. The efficiency of the correction method is compared with that produced by the traditional method without introduction of an error function.Three test cases are presented in this study in order to compare the performances of the proposed methods. In the first two tests, the reference is the analytical solution and the last test is formulated as part of the “twin experiment”.The numerical results obtained confirm the important role of the model error equation for improving the prediction capability of the system, in terms of both accuracy and speed of convergence.     

Target Design of Novel Histone Deacetylase 6 Selective Inhibitors with 2-Mercaptoquinazolinone as the Cap Moiety

Epigenetic alterations found in all human cancers are promising targets for anticancer therapy. In this sense, histone deacetylase inhibitors (HDACIs) are interesting anticancer agents that play an important role in the epigenetic regulation of cancer cells. Here, we report 15 novel hydroxamic acid-based histone deacetylase inhibitors with quinazolinone core structures. Five compounds exhibited antiproliferative activity with IC₅₀ values of 3.4–37.8 µM. Compound 8 with a 2-mercaptoquinazolinone cap moiety displayed the highest antiproliferative efficacy against MCF-7 cells. For the HDAC6 target selectivity study, compound 8 displayed an IC₅₀ value of 2.3 µM, which is 29.3 times higher than those of HDAC3, HDAC4, HDAC8, and HDAC11. Western blot assay proved that compound 8 strongly inhibited tubulin acetylation, a substrate of HDAC6. Compound 8 also displayed stronger inhibition activity against HDAC11 than the control drug Belinostat. The inhibitory mechanism of action of compound 8 on HDAC enzymes was then explored using molecular docking study. The data revealed a high binding affinity (−7.92 kcal/mol) of compound 8 toward HDAC6. In addition, dock pose analysis also proved that compound 8 might serve as a potent inhibitor of HDAC11.     

Solution to the Neumann problem exterior to a prolate spheroid by radial basis functions

We consider the exterior Neumann problem of the Laplacian with boundary condition on a prolate spheroid. We propose to use spherical radial basis functions in the solution of the boundary integral equation arising from the Dirichlet–to–Neumann map. Our approach is particularly suitable for handling of scattered data, e.g. satellite data. We also propose a preconditioning technique based on domain decomposition method to deal with ill-conditioned matrices arising from the approximation problem.