Indium-Mediated Preparation of Bis(α-hydroxyallenes) or α,α'-Dihydroxyallenynes and Further Gold-Catalyzed Cyclizations.

We present the regio- and diastereoselective Barbier-type allenylation reaction of glyoxals mediated by indium to furnish highly valuable -bis(α-hydroxyallenes) and -α,α'-dihydroxyallenynes. The gold-catalyzed controlled cyclization of these unsaturated diols enables the divergent preparation of three types of oxacycles.

Contilisant+Tubastatin A Hybrids: Polyfunctionalized Indole Derivatives as New HDAC Inhibitor-Based Multitarget Small Molecules with and Activity in Neurodegenerative Diseases.

Herein, we describe the design, synthesis, and biological evaluation of 15 + hybrids. These ligands are polyfunctionalized indole derivatives developed by juxtaposing selected pharmacophoric moieties of and to act as multifunctional ligands. Compounds and were identified as potent HDAC6 inhibitors (IC = 0.

The proof of concept of 2-{3-[N-(1-benzylpiperidin-4-yl)propyl]amino}-6-[N-methyl-N-(prop-2-yn-1-yl)amino]-4-phenylpyridine-3,5-dicarbonitrile for the therapy of neuropathic pain.

In the search for new small molecules for the therapy of neuropathic pain, we found that 2-{3-[N-(1-benzylpiperidin-4-yl)propyl]amino}-6-[N-methyl-N-(prop-2-yn-1-yl)amino]-4-phenylpyridine-3,5-dicarbonitrile (12) induced a robust antiallodynic effect in capsaicin-induced mechanical allodynia, a behavioural model of central sensitization, through σR antagonism. Furthermore, administration of compound 12 to neuropathic animals, fully reversed mechanical allodynia, increasing its mechanical threshold to levels that were not significantly different from those found in paclitaxel-vehicle treated mice or from basal levels before neuropathy was induced. Ligand 12 is thus a promising hit-compound for the therapy of neuropathic pain.

Unveiling the Use of 1,1-Bis(triflyl)ethylene as CFSOCH═CH Source with the Assistance of (-Bu)NF: Synthesis of 3-[(Trifluoromethyl)sulfonyl]cyclobut-1-enes.

Allylic sulfone-embedded cyclobutenes have been prepared in one pot from alkynes. The carbocycle and the alkenyl sulfone moieties were installed through consecutive bis(triflyl)cyclobutenylation of a triple bond and tetra--butylammonium fluoride (TBAF)-assisted hydrodesulfonylation of an allylic bis(sulfone). It is noteworthy that 1,1-bis(triflyl)ethylene acts as a CFSOCH═CH source for the first time.

Straightforward Synthesis of Bis[(trifluoromethyl)sulfonyl]ethylated Isocoumarins from 2-Ethynylbenzoates.

Herein, we report a facile isocoumarin and isoquinolone preparation by taking advantage of an initial bis(triflyl)ethylation [triflyl = (trifluoromethyl)sulfonyl] reaction, followed by heterocyclization, which contrasts with our previous results on cyclobutene formation. The efficiency of the catalyst- and irradiation-free heterocyclization/bis(triflyl)ethylation sequence showed exquisite dependence on the electronic nature of the substituents at the 2-ethynylbenzoate(benzamide) precursors. Molecular docking of model bis(triflyl)ethylated isocoumarins on human acetylcholinesterase (hAChE) revealed promising biological activities through selective coordination on both the catalytic active site and peripheral active site.

Both Zn biofortification and nutrient distribution pattern in cherry tomato plants are influenced by the application of ZnO nanofertilizer.

A pot experiment was conducted to determine the influence of commercial nanoparticles (ZnO-NPs) at different doses for use as nanofertilizer on nutrient uptake and its distribution in cherry tomato ( L var. cerasiforme) plants in an acidic (soil pH 5.5) and calcareous soil (soil pH 8.

Synthesis of Polycyclic Aromatic Hydrocarbons Decorated by Fluorinated Carbon Acids/Carbanions.

The carboarylation reaction of biphenyl-alkynes was successfully triggered by electrophilic attack of 1,1-bis(triflyl)ethylene on the alkyne moiety to give polycyclic aromatic hydrocarbons (PAHs) decorated by superacidic carbon acid functionality. Neutralisation of thus obtained acids with NaHCO yielded the corresponding sodium salts, which showed improved solubility in both aqueous and organic solvents.

A Convenient Formal [4+2] Heterocylization Route to Bis(triflyl)tetrahydroquinolines.

We report the sustainable and efficient synthesis of a new type of quinoline derivatives bearing one or two SO CF groups. The protocol is metal-, catalyst- and irradiation-free, involves the use of readily available and stable precursors, and avoids the formation of side products. Also, the mild conditions of the process allow the tolerance of a wide range of functional groups.

Pd-catalyzed C(sp)-C(sp) bond formation in iodocyclobutenes.

A synthesis of skipped 1,4-enynes through functionalization of the cyclobutene core with alkynes has been achieved, suggesting an unusual pathway of oxidative addition in tertiary iodoalkanes.

Metal-Free C-C/C-N/C-C Bond Formation Cascade for the Synthesis of (Trifluoromethyl)sulfonylated Cyclopenta[]indolines.

A bis(triflyl)ethylation [triflyl = (trifluoromethyl)sulfonyl] inserted into a sequential cyclization cascade resulted in the direct formation of -bis(triflyl)ated cyclopenta[]indolines from anilide-derived allenols and alkenols. This catalyst- and irradiation-free sequence facilitated the efficient preparation of functionalized tricyclic indoline cores bearing two contiguous stereocenters. The formed cyclopenta[]indolines can be easily transformed into a wide variety of triflylated indolines, including the tetracycle ring system found in polyveoline.

GOECP/SEOR radiotherapy guidelines for small-cell lung cancer.

Small cell lung cancer (SCLC) accounts for approximately 20% of all lung cancers. The main treatment is chemotherapy (Ch). However, the addition of radiotherapy significantly improves overall survival (OS) in patients with non-metastatic SCLC and in those with metastatic SCLC who respond to Ch.

Deciphering the Chameleonic Chemistry of Allenols: Breaking the Taboo of a Onetime Esoteric Functionality.

The allene functionality has participated in one of the most exciting voyages in organic chemistry, from chemical curiosities to a recurring building block in modern organic chemistry. In the last decades, a special kind of allene, namely, allenol, has emerged. Allenols, formed by an allene moiety and a hydroxyl functional group with diverse connectivity, have become common building blocks for the synthesis of a wide range of structures and frequent motif in naturally occurring systems.

Visible-Light-Mediated Ru-Catalyzed Synthesis of 3-(Arylsulfonyl)but-3-enals via Coupling of α-Allenols with Diazonium Salts and Sulfur Dioxide.

The first coupling of α-allenols, sulfur dioxide, and arenediazonium salts is presented. The three-component reaction which is promoted by visible light can be easily accomplished using DABSO as a sulfur dioxide surrogate in the presence of a photoredox catalyst. In this manner, a broad range of electron-rich and electron-deficient aryl substituents are well accommodated in the sulfonylation-rearrangement cascade to afford the 2,2-disubstituted 3-(arylsulfonyl)but-3-enals in reasonable yields.

Trifluorosulfonylation Cascade in Allenols: Stereocontrolled Synthesis of Bis(triflyl)enones.

Herein, we report investigations embodying the first example of reversal of the native regioselectivity in the reaction of allenols with electrophiles. The effortlessness of C-C bond formation, mild reaction conditions, neither catalysts nor light irradiation, and exquisite selectivity, both in terms of functional-group tolerance and chemo-, site-, and stereo-selectivity, converts this trifluorosulfonylation-rearrangement sequence into an appealing protocol for the preparation of novel functionalized enones. The synthetic utility of this method has been validated by the conversion of the initially prepared bis(triflyl)enones into a variety of bis(triflyl)-functionalized molecules such as 1,3-dienes, allylic alcohols, pyrroles, pyrazoles, and chromenes.

Triflyl-assisted reductive Pd-catalyzed Tsuji-Trost type reaction.

New (triflyl)cyclobutenes have been prepared by palladium-catalyzed hydrodetriflylation reaction using water and deuterium oxide as convenient hydrogen and deuterium sources. In addition, an investigation of the possible mechanism for this Tsuji-Trost type reaction of bis(triflyl)cyclobutenes has been facilitated by labelling studies and density functional theory (DFT) calculations.

Organoseleno-Catalyzed Synthesis of α,β-Unsaturated α'-Alkoxy Ketones from Allenes Enabled by Se···O Interactions.

α,β-Unsaturated α'-alkoxy ketones have been prepared under mild conditions from allenes using water as the oxygen source and without the necessity of metals. The organocatalytic oxygenation-rearrangement sequence displays an exquisite chemo-, stereo-, and site-selectivity as well as good functional group compatibility. DFT calculations suggest that stabilizing noncovalent Se···O interactions may be responsible for the observed reactivity.

A catalyst-free bis(triflyl)ethylation/benzannulation reaction: rapid access to carbazole-based superacidic carbon acids from alkynols.

Carbazoles possessing TfCHCH groups were obtained by the reaction of 1-(indol-2-yl)but-3-yn-1-ols with in situ-generated TfC[double bond, length as m-dash]CH through vicinal difunctionalisation of the alkyne moiety, where the vinyl-type carbocation intermediate was selectively attacked by the indole moiety and not by the carbanion moiety.

Transition metal-free cyclobutene rearrangement in fused naphthalen-1-ones: controlled access to functionalized quinones.

The controlled synthesis of 1,4-naphthoquinones and tetraphene-7,12-diones, which bear the ABCD-ring of landomycins, has been accomplished directly through oxidative rearrangement of common stable precursors, namely, previously non-isolable cyclobuta[a]naphthalen-4(2H)-ones.

Effect of ageing of bare and coated nanoparticles of zinc oxide applied to soil on the Zn behaviour and toxicity to fish cells due to transfer from soil to water bodies.

This study evaluated the influence of ageing of ZnO nanoparticles (NPs) applied to soil on the potential availability and chemical speciation of Zn, and also of their toxicity to aquatic organisms due to transfer of contaminants from soil to water. To this end, soil samples were spiked with two types of bare nanoparticles: b1ZnO NPs (rod- and elongated-shaped) and b2ZnO NPs (near-spherical shaped) and ZnO NPs coated with (3-aminopropyl)triethoxysilane (cZnO NPs) within the 0-800 mg Zn kg soil dose range, and were left to age for 0, 30, 60 and 90 days. The available concentration and speciation of Zn in soil were determined by the DGT (diffusive gradients in thin films) technique and sequential extraction procedures, respectively.

Joint effects of zinc oxide nanoparticles and chlorpyrifos on the reproduction and cellular stress responses of the earthworm Eisenia andrei.

The co-exposure of soil organisms to ZnO nanoparticles (ZnO NPs) and pesticides is likely to take place in agricultural soils. However, the impacts of co-exposure on terrestrial ecosystems are virtually unknown. In this paper, Eisenia andrei was exposed for a 28-day period to serial concentrations of ZnO NPs and/or the organophosphate insecticide chlorpyrifos (CPF) in natural soil, and was evaluated for single and joint effects.

Zinc application in conjunction with urea as a fertilization strategy for improving both nitrogen use efficiency and the zinc biofortification of barley.

Background: Intensive cropping systems have caused widespread Zn deficiency, low nutritional quality of cereals and environmental problems. The aim of the microplot field experiment reported in this paper was to assess the option of using Zn in conjunction with urea fertilization in order to reduce N rate and to maintain the yield level and grain quality but minimizing environmental risks. Barley (Hordeum vulgare L.

Convenient Access to 2,3-Disubstituted-cyclobut-2-en-1-ones under Suzuki Conditions and Their Synthetic Utility.

A regioselective synthesis of general applicability has been designed for the one-pot preparation of 2,3-disubstituted-cyclobutenones from iodoalkynes through cyclobutenylation, Suzuki CC coupling, and ketone formation. This one-pot methodology has been applied to the selective synthesis of an orally active cyclooxygenase II inhibitor. Furthermore, the obtained cyclobut-2-en-1-ones were used as synthons in several transformations, such as, the preparation of β-lactams, phthalazines, cyclohexa-2,5-dien-1-ones, and cyclopent-3-en-1-ones.

Synthesis and Characterization of Stable Phosphorus Carbabetaines.

Phosphorus 1,3- and 1,4-carbabetaines with 'P(+)-C-C(-)' and 'P(+)-C-C-C(-)' structures, respectively, in which the carbanion moiety was significantly stabilized by two trifluoromethylsulfonyl groups, have been synthesized and characterized. Analysis of their X-ray crystal structures revealed that any attractive interactions between the anionic and cationic moieties were negligibly weak. This result was corroborated by using natural bond orbital (NBO) and Bader's quantum theory of atoms in molecules (QTAIM) models.

Divergence in Ynone Reactivity: Atypical Cyclization by 3,4-Difunctionalization versus Rare Bis(cyclization).

Functionalized ynones can be activated by Tf C=CH , which was generated in situ, to form zwitterionic species. These species were trapped in an intramolecular fashion by several nucleophiles to generate two major types of triflones in a divergent manner. Through fine-tuning of the reaction temperature, bis(triflyl)-6-membered- or (triflyl)-5-membered-fused-heterocycles were achieved in reasonable yields in a totally selective manner.