Electrochemical 1,2-Diarylation of Alkenes Enabled by Direct Dual C-H Functionalizations of Electron-Rich Aromatic Hydrocarbons.

A cobalt-promoted electrochemical 1,2-diarylation of alkenes with electron-rich aromatic hydrocarbons via direct dual C-H functionalizations is described, which employs a radical relay strategy to produce polyaryl-functionalized alkanes. Simply by using graphite rod cathode instead of platinum plate cathode, chemoselectivity of this radical relay strategy is shifted to the dehydrogenative [2+2+2] cycloaddition via 1,2-diarylation, annulation, and dehydrogenation cascades leading to complex 11,12-dihydroindolo[2,3-a]carbazoles. Mechanistical studies indicate that a key step for the radical relay processes is transformations of the aromatic hydrocarbons to the aryl sp2 -hybridized carbon-centered radicals via deprotonation of the corresponding aryl radical cation intermediates with bases.

Design, synthesis and biological evaluation of ring-fused pyrazoloamino pyridine/pyrimidine derivatives as potential FAK inhibitors.

We report herein the synthesis of novel ring-fused pyrazoloamino pyridine/pyrimidine derivatives as potential FAK inhibitors and the evaluation of pharmaceutical activity against five cancer cell lines (MDA-MB-231, BXPC-3, NCI-H1975, DU145 and 786O). Generally, the majority of compounds displayed strong anti-FAK enzymatic potencies (IC50 < 1 nM) and could effectively inhibit several class of cancer cell lines within the concentration of 3 µM in comparison with GSK2256098 as a reference. Among them, compound 4o is considered to be the most effective due to high sensitivity in antiproliferation. In culture, 4o could not only inhibit FAK Y397 phosphorylation in MDA-MB-231 cell line, but also trigger apoptosis in a dose-dependent manner. Furthermore, computational docking analysis also suggested that 4o and TAE-226 displayed the similar interaction with FAK kinase domain.

Benzylic C-H heteroarylation of N-(benzyloxy)phthalimides with cyanopyridines enabled by photoredox 1,2-hydrogen atom transfer.

A visible light initiated α-C(sp3)-H arylation of N-(benzyloxy)phthalimides with cyanopyridines for the construction of highly valuable pyridinyl-containing diarylmethanols, including bioactive motif-based analogues, is reported. This method enables arylation of the C(sp3)-H bonds adjacent to an oxygen atom through alkoxy radical formation by O-N bond cleavage, 1,2-hydrogen atom transfer (HAT), arylation and C-CN bond cleavage cascades, and offers a means to exploit 1,2-HAT modes to incorporate functional groups for constructing functionalized alcohols.

Copper-Catalyzed Oxidative Alkylation (Methylation) of Phosphonamides and Phosphinamides Using Dicumyl Peroxide.

An effective and practical CuI-catalyzed methodology toward N-alkyl or N-methyl phosphonamides and phosphinamides was herein demonstrated. The transformation took place readily under the oxidative conditions, and plenty of N-alkylated (methylated) amides (30 examples) were successfully furnished in high efficiency (up to 92% yields). Dicumyl peroxide was considered to act either as the oxidant for the alkylation reaction or as methyl donator for the methylation protocol.

Copper-Promoted Desulfitative N-Arylation of Sulfonamides and Sulfoximines with Sodium Arylsulfinates.

A general and direct N-arylation of sulfonamides and NH-sulfoximines by sodium arylsulfinates through a desulfitative pathway was herein demonstrated. The reaction proceeded with catalytic loadings of Cu(II)-catalysts without any external ligands. And the novel arylation protocol featured for high efficiency (up to 93% yields) and good substituent tolerance (up to 53 examples). Moreover, a plausible reaction mechanism was also discussed.

Anti-inflammatory effects of novel sinomenine derivatives.

Sinomenine is an isoquinoline-type alkaloid found in Sinomenium acutum (Thunb.) Rehd. et Wils and S. acutum (Thunb.) Rehd. et Wils var. cinereum Rehd. et Wils. When used as a medicine, this compound exhibits anti-inflammatory properties; however, sinomenine's use as a medication is limited by side effects, a short half-life, and low efficacy. Owing to these limits, attempts have been made to synthesize sinomenine derivatives with enhanced efficacy. In this study, the anti-inflammatory effects of novel sinomenine derivatives (S1a-S1f) were examined on the basis of lipopolysaccharide-induced inflammatory factor expression in Raw264.7 cells, dimethylbenzene-induced ear oedema, and Evan's blue leakage in mice, and carrageenan-induced paw oedema in rats. Compared with sinomenine, the derivatives significantly inhibited the expression of the inflammatory factors IL-1ß and IL-6 at the transcriptional and translational levels. Topical application of 3.250mg/kg of the derivatives also alleviated ear oedema. Compared with the vehicle, the derivatives significantly inhibited carrageenan-induced rat paw oedema after 6h. Among the derivatives, S1a exhibited the most potent anti-inflammatory activity. S1a also significantly increased the sinomenine-induced inhibition of Evan's blue leakage. Thus, S1a may elicit the strongest anti-inflammatory effects of the tested compounds. Based on these results, further development of this compound may be warranted.

Transition metal-free aroylation of NH-sulfoximines with methyl arenes.

A novel protocol towards N-aroylated sulfoximines from NH-sulfoximines and methyl arenes was herein demonstrated. The reaction took place in the presence of elemental iodine, requiring no external organic solvents, transition metal-catalysts or ligands. The aroylated products were obtained from the oxidative transformation in moderate to excellent yields (up to 94% yield) with a broad substrate scope (35 examples) through a radical pathway.

2,6-Bis(4-meth-oxy-phen-yl)-1,4-dithiine.

The title mol-ecule, C18H16O2S2, reveals crystallographic twofold rotation symmetry (with both S atoms lying on the axis) and one half-mol-ecule defines an asymmetric unit. The dithiine ring is in a boat conformation. The aromatic ring and the C=C bond are nearly coplanar, with small torsion angles of -171.26 (19) and 8.5 (3)°. The two S-C bond lengths [1.7391 (19) and 1.7795 (18) Å] are shorter than single C-S bonds and longer than analogous C=S double bonds, which indicates a certain degree of conjugation between the lone pair on the S atom and π electrons of the C=C bond. The crystal packing only features van der Waals inter-actions.

Synthesis of haptens and development of an indirect enzyme-linked immunosorbent assay for tris(2,3-dibromopropyl) isocyanurate.

A competitive indirect enzyme-linked immunosorbent assay (ciELISA) was developed for detection of tris(2,3-dibromopropyl) isocyanurate (TBC). Polyclonal antibodies against TBC were raised from synthesized haptens and then screened against various coating antigens. After optimization of the immunoassay conditions, the linear range and IC50 value of the assay were 0.30-100 and 5.17 µg/L, respectively, with little cross-reactivity (≤2%). Recovery of various samples (water, serum, soil) was tested and the values ranged from 68% to 110%. This ciELISA was also applied to determine TBC in the riverside soil of the Liuyang River, and the results were compared with the data obtained by UHPLC-MS/MS. The experimental assay results confirmed that this proposed immunoassay is a specific, sensitive, and reliable method for determination and monitoring of TBC.

Synthesis of haptens and selective enzyme-linked immunosorbent assay of octachlorostyrene.

A sensitive, competitive indirect enzyme-linked immunosorbent assay (ELISA) was developed for the detection of octachlorostyrene (OCS), a persistent and bioaccumulative toxicant. To achieve the most sensitive antibody, several haptens with different linkers that simulated the special structure of OCS were synthesized and conjugated to carrier proteins. Polyclonal rabbit antibodies against different immunizing antigens were obtained and screened against different coating antigens. Under the optimized conditions, this indirect ELISA shows a linear detection range from 1.4 to 86.3 ng/mL, with an IC50 value of 4.46 ng/mL and a limit of detections (LOD) of 0.1 ng/mL. Twelve kinds of compounds were tested for calculating cross-reactivities, and almost all of them showed little cross-reactivity (<5%). Water and sera samples spiked with OCS were analyzed by ELISA and the achieved recoveries were satisfied with a mean recovery of 92%. This immunoassay can be used as a rapid and convenient tool to monitoring OCS in environmental samples.

1,3-Alternate conformer 5,11,17,23-tetra-tert-butyl-25,26,27,28-tetra-kis-(4-methyl-sulfanylbenz-yloxy)-2,8,14,20-tetra-thia-calix[4]arene.

The title thia-calix[4]arene derivative, C72H80O4S8, adopts a 1,3-alternate conformation, where the four 4-methyl-sul-fan-yl-benzyl groups are located alternately at the two sides of a virtual plane defined by the four bridging S atoms. In the crystal, there are no significant inter-molecular inter-actions present. Some of the peripheral tert-butyl and methyl-sulfanyl groups are disordered over two positions. A region of disordered electron density, occupying voids of ca 700 Å(3) for an electron count of 124, was treated using the SQUEEZE routine in PLATON [Spek (2009 ▶). Acta Cryst. D65, 148-155].

5,11,17,23-Tetra-kis(1,1-di-methyl-eth-yl)-26,28-di-hydroxy-calix[4]arene-25,27-mono-thia-crown-3.

The title calix[4]arene compound [systematic name: 3,9,15,34-tetra-tert-butyl-19,29-dioxa-24-thia-hexa-cyclo-[15.13.7.1(7,11).1(32,36).0(5,30).0(13,18)]nona-triaconta-1(30),2,4,7,9,11(39),13,15,17,32,34,36(38)-dodeca-ene-38,39-diol], C52H70O4S, displays a cone-like conformation, the opposite arene rings bridged by the mono-thia-crown-3 unit are nearly parallel [dihedral angle = 16.01 (18)°], whereas the other opposite arene rings are twisted to each other at an angle of 74.41 (17)°. Intra-molecular O-H⋯O hydrogen bonds help to stabilize the mol-ecular structure. In the crystal, a C-H⋯π inter-action occurs. One of the tert-butyl groups is disordered over two sets of sites with a site-occupancy ratio of 0.70:0.30.

Cationic recognition by tert-butylcalix[4]arene-functionalized nanoprobes.

A nanoparticle-based strategy has been demonstrated using structurally-tailored tert-butylcalixarenes immobilized on gold nanoparticles to tune the guest access to the calixarene cone cavity for cationic recognition. This strategy exploits the interparticle charge-induced aggregation upon selective capture of metal cations into the nanoparticle-immobilized tert-butylcalixarenes, which produces calorimetric changes for the detection. A possible pathway for the binding of M(n+) into the t-BCA structure and the interparticle interaction is proposed for the formation of an electric double layer inducing the interparticle association responsible for the red-shifted surface plasmon resonance band of the nanoparticles. The value of this class of calorimetric nanoprobes will be in the area of designing advanced host-guest probes using a variety of calixarene ligands for ionic recognition in a simplistic detection format.

Molecularly-mediated assembly of gold nanoparticles with interparticle rigid, conjugated and shaped aryl ethynyl structures.

The rigidity, conjugation, and shape-persistent architectures of aryl ethynyls of V, Y, and X shapes serve as an ideal model system for defining interparticle structures, which have been demonstrated for the mediated assembly of gold nanoparticles.

Synthesis and structure of an extremely air-stable binuclear hafnocene perfluorooctanesulfonate complex and its use in Lewis acid-catalyzed reactions.

Stable complexes: An extremely air-stable mu(2)-hydroxy-bridged binuclear hafonocene perfluorooctanesulfoante complex shows high catalytic efficiency in Lewis acid-catalyzed reactions, such as esterification, Friedel-Crafts acylation, the Mukaiyama aldol reation, and the allylation of aldehyde (see scheme).An extremely air-stable mu(2)-hydroxy-bridged binuclear hafonocene perfluorooctanesulfoante complex was successfully synthesized. This complex showed high catalytic efficiency in the esterification of alcohols, phenol, thiol, and amines, in the Friedel-Crafts acylation of alylaryl ethers, in the Mukaiyama aldol reaction, and in the allylation of aldehydes and could be reused.

Synthesis and structure of air-stable Lewis acidic binuclear complex of zirconocene pentafluorophenylsulfonate and its catalytic application in the allylation of carbonyl compounds with tetraallyltin.

Air-stable Lewis acidic micro2-hydroxy bridged binuclear complex of zirconocene pentafluorophenylsulfonate was successfully synthesized and found to show high catalytic efficiency in chemoselective allylation of carbonyl compounds with tetraallyltin in aqueous methanol media.

Enantiopure double-helical phenylene ethynylene cyclophynes with the 2,2'-binaphthyl template.

New types of enantiopure compounds were synthesized to gain better insight into the structural features of phenylene ethynylene cyclophynes. Besides the previously obtained meta-substituted arylene ethynylenes, 1, ortho-connected phenylene ethynylene units were incorporated to give cyclophynes with ortho/meta and ortho/ortho connection modes, 2 and 3. Furthermore, a diphenylethyne component was also accommodated in 4. Both ab initio calculations and NMR spectra suggest a large amount of strain for 2 but less strain for 3 and 1 a, the latter having the smallest ring size among cyclophynes with the meta/meta connection mode. The CD spectra of 2 and 3 showed a characteristic shoulder at around 340 nm, similar to the case of 1 a. This implies that the aromatic acetylene bonds cross over each other in the double-helical structure. These results indicate that chirality information is useful for probing the persistency of molecular shape.