Rational design of resorcylic acid lactone analogues as covalent MNK1/2 kinase inhibitors by tuning the reactivity of an enamide Michael acceptor.

Recent biological and computational advances in drug design have led to renewed interest in targeted covalent inhibition as an efficient and practical approach for the development of new drugs. As part of our continuing efforts in the exploration of the therapeutic potential of resorcylic acid lactones (RALs), we report herein the design, synthesis, and biological evaluation of conveniently accessible RAL enamide analogues as novel covalent inhibitors of MAP kinase interacting kinases (MNKs). In this study, we have successfully demonstrated that the covalent binding ability of RAL enamides can be tuned by attaching an electron-withdrawing motif, such as an acyl group, to enhance its reactivity toward the cysteine residues at the MNK1/2 binding sites.

Water swelling, brine soluble imidazole based zwitterionic polymers--synthesis and study of reversible UCST behaviour and gel-sol transitions.

New vinylbenzene substituted imidazole based zwitterionic polymers with unique characteristics like swelling in water and solubility in concentrated brine solution in which they exhibited a reversible upper critical solution temperature (UCST) and gel-sol transitions are reported herein.

Regioselective copper-catalyzed carboxylation of allylboronates with carbon dioxide.

In the presence of a Cu(I)/NHC catalyst, the reactions of allylboronic pinacol esters with CO2 (1 atm) are highly regioselective, giving exclusively the more substituted β,γ-unsaturated carboxylic acids in most cases. A diverse array of substituted carboxylic acids can be prepared via this method, including compounds featuring all-carbon quaternary centers.

Application of mid-infrared chemical imaging and multivariate chemometrics analyses to characterise a population of microalgae cells.

A suite of multivariate chemometrics methods was applied to a mid-infrared imaging dataset of a eustigmatophyte, marine Nannochloropsis sp. microalgae strain. This includes the improved leader-follower cluster analysis (iLFCA) to interrogate spectra in an unsupervised fashion, a resonant Mie optical scatter correction algorithm (RMieS-EMSC) that improves data linearity, the band-target entropy minimization (BTEM) self-modeling curve resolution for recovering component spectra, and a multi-linear regression (MLR) for estimating relative concentrations and plotting chemical maps of component spectra.

Direct conversion of indoles to 3,3-difluoro-2-oxindoles via electrophilic fluorination.

3,3-Difluoro-2-oxindoles can be obtained directly from indoles in moderate yields via electrophilic fluorination using N-fluorobenzenesulfonimide as a mild fluorinating reagent. The presence of tert-butyl hydroperoxide during the reaction, together with additional heating after quenching the reaction with triethylamine, is beneficial to the formation of the desired product.

Atmospheric pressure aminocarbonylation of aryl iodides using palladium nanoparticles supported on MOF-5.

An efficient amide synthesis by atmospheric pressure aminocarbonylation using palladium nanoparticles supported on MOF-5 is reported. Interestingly, only 0.5 wt% palladium loading was required to achieve high yields.

Exploring aigialomycin d and its analogues as protein kinase inhibitors for cancer targets.

The natural product aigialomycin D (1) is a member of the resorcylic acid lactone (RAL) family possessing protein kinase inhibitory activities. This paper describes the synthesis of aigialomycin D and a series of its analogues and their activity for the inhibition of protein kinases related to cancer pathways. A preliminary study of these compounds in the inhibition of CDK2/cyclin A kinase has found that aigialomycin D and analogues 11 and 23 are moderate CDK2/cyclin A inhibitors with IC50 values of ca.

Total synthesis of echinopines A and B: exploiting a bioinspired late-stage intramolecular cyclopropanation.

Total synthesis of echinopine A and B have been accomplished, based on a strategy that involved two transition-metal-mediated ene-yne cycloisomerizations. A modified Pd-catalyzed enyne cycloisomerization/intramolecular Diels-Alder cascade rendered a more streamlined synthesis of tricyclic ketone 15, and a Ru-catalyzed ene-yne cycloisomerization/cyclopropanation resembled the late-stage [5/7] → [3/5/5/7] ring-forming sequence in the proposed biosynthetic pathway.

A modular synthesis of salvileucalin B structural domains.

A modular strategy leading to the salvileucalin B core structure has been accomplished. The developed synthetic strategy featured a bioinspired intramolecular Diels-Alder reaction to construct domain "A", REDOX chemistry to functionalize domain "B", and a palladium-mediated cross-coupling to install domain "C". This flexible approach should facilitate further chemical and biological investigations of this fascinating class of compounds.

Modular synthesis of polyphenolic benzofurans, and application in the total synthesis of malibatol a and shoreaphenol.

A modular strategy for the synthesis of hexacyclic dimeric resveratrol polyphenolic benzofurans is reported. The developed synthetic technology was applied to the total synthesis of malibatol A, shoreaphenol, and other biologically relevant poly-phenols.

Total synthesis of englerin A.

Total synthesis of englerin A, a recently reported sesquiterpenoid exhibiting potent and selective growth inhibition against renal cancer cell lines, has been accomplished. The successful strategy featured a [5 + 2] cycloaddition reaction to cast the seven-membered oxabicyclic key intermediate in both racemic and optically active forms. Synthetic (+/-)-englerin A, (+/-)-englerin B, (+/-)-englerin B acetate, a hydroxy acetate, a tert-butyldimethylsilyl ether, and hydrogenated (+/-)-englerin A (31) were tested for their cytotoxicity against a selected panel of cancer cell lines, and the results are path-pointing to more focused structure-activity relationship studies.

Excellent performance in lithium-ion battery anodes: rational synthesis of Co(CO3)0.5(OH)0.11H2O nanobelt array and its conversion into mesoporous and single-crystal Co3O4.

Herein, we report a rational method to synthesize a Co3O4 nanobelt array on a conducting substrate and functionalize it in the application of Li-ion battery anodes, which is a novel and facile approach to access the nanobelt array of transition metal oxides. Compared to the previous reports, the as-prepared samples in our experiments exhibited both mesoporosity and single-crystallinity, and meanwhile, good contact with the conducting substrate (via a thin layer of TiO2) provided an express pathway for charge transfer when they were applied in Li-ion batteries without any need to add other ancillary materials (carbon black or binder) to enhance the system's conductivity and stability. Under the condition of high charge-discharge current density of 177 mA/g in Li-ion batteries' testing, the Co3O4 nanobelt array was capable of retaining the specific capacity of 770 mAh/g over 25 cycles.

Total synthesis and biological evaluation of cortistatins A and J and analogues thereof.

Total syntheses of the highly selective antiproliferative natural products cortistatins A (1) and J (5) in their naturally occurring enantiomeric forms are described. The modular and convergent strategy employed relies on an intramolecular oxa-Michael addition/aldol/dehydration cascade reaction to cast the ABCD ring framework of the molecule and both Sonogashira and Suzuki-Miyaura coupling reactions to assemble the necessary building blocks into the required heptacyclic skeleton. A divergent approach from a late-stage epoxy ketone leads to both target molecules in a stereoselective manner.

Hierarchical band-target entropy minimization curve resolution and Pearson VII curve-fitting analysis of cellular protein infrared imaging spectra.

A soft-modeling multivariate numerical approach that combines self-modeling curve resolution (SMCR) and mixed Lorentzian-Gaussian curve fitting was successfully implemented for the first time to elucidate spatially and spectroscopically resolved spectral information from infrared imaging data of oral mucosa cells. A novel variant form of the robust band-target entropy minimization (BTEM) SMCR technique, coined as hierarchical BTEM (hBTEM), was introduced to first cluster similar cellular infrared spectra using the unsupervised hierarchical leader-follower cluster analysis (LFCA) and subsequently apply BTEM to clustered subsets of data to reconstruct three protein secondary structure (PSS) pure component spectra-alpha-helix, beta-sheet, and ambiguous structures-that associate with spatially differentiated regions of the cell infrared image. The Pearson VII curve-fitting procedure, which approximates a mixed Lorentzian-Gaussian model for spectral band shape, was used to optimally curve fit the resolved amide I and II bands of various hBTEM reconstructed PSS pure component spectra.

Observation of the ammonium salt of 12-molybdophosphoric acid by in situ Raman spectroscopy during solid-state synthesis: spectral analysis and reconstruction using the band-target entropy minimization (BTEM) algorithm.

The solid-state reaction between ammonium heptamolybdate (AHM) and zirconium phosphate (ZrP) to give the ammonium salt of 12-molybdophosphoric acid (AMPA) was performed at 25-400 degrees C and monitored using in situ Raman spectroscopy. Spectral analysis of the Raman data using the band-target entropy minimization (BTEM) algorithm resulted in spectral estimates for the starting materials and product, AHM, ZrP, and AMPA, as well as the byproduct MoO3 and an intermediate 11(NH4)2O.4(MoO3)7.

Utilization of spectral vector properties in multivariate chemometrics analysis of hyperspectral infrared imaging data for cellular studies.

A suite of numerical techniques was utilized in a concerted fashion for the efficacious multivariate chemometrics analysis of hyperspectral infrared imaging data of exfoliated oral mucosa cells. Based on the vector representation of infrared spectrum a1xnu), spectral vector properties (SVP) are demonstrated to possess underpinning spectral information that was exploited in crucial chemometrics analyses; which include outlier spectra identification, selection for a subset of imaged mid-infrared spectra that contain good oral mucosa cell signals, and, for the first time, obtain major biochemical constituent spectra via the band-target entropy minimization (BTEM) curve resolution algorithm. The relative concentration spatial distribution of the major biochemical constituents observed, namely membrane lipids and various cellular protein structures (alpha-helix, beta-sheet, turns and bends), were subsequently acquired through multi-linear regression and were displayed as chemical contour maps.

An expedient asymmetric synthesis of platencin.

A short and efficient synthesis of enone 3, a key intermediate in the total synthesis of platencin (2), based on an intramolecular Diels-Alder reaction is described.

Chemical synthesis and biological evaluation of palmerolide A analogues.

Molecular design and chemical synthesis of several palmerolide A analogues allowed the first structure activity relationships (SARs) of this newly discovered marine antitumor agent. From several analogues synthesized and tested (ent- 1, 5- 14, 21- 26, 50, 51), compounds 25 (with a phenyl substituent on the side chain) and 51 (lacking the C-7 hydroxyl group) were the most interesting, exhibiting approximately a 10-fold increase in potency and equipotency, respectively, to the natural product. These findings point the way to more focused structure activity relationship studies.

Latest developments in the catalytic application of nanoscaled neutral group 8-10 metals.

In the last few decades, the synthesis and catalytic application of nanoscaled particles prepared from Group 8-10 (formerly Group VIIIB) elements have been widely explored and have achieved promising results. The innovative use of these nanoparticle catalysts may provide new opportunities in the efficient combination of conventionally used homogenous and heterogeneous catalysts. Conventional homogeneous catalysts pose extraction and recycling difficulties when dealing with metal complexes and/or ligands, whereas heterogeneous catalysts generally require more pressing experimental conditions, such as high temperatures and high pressures, to be effective.