Iodine-Catalyzed Cyclization of o-Nitrothiophenols with Cyclohexanones to Phenothiazines.

Here, a novel iodine-catalyzed direct cyclization of o-nitrothiophenols with cyclohexanones to phenothiazines has been described without external oxidants and hydrogen acceptors. The nitro of o-nitrothiophenol works as both a hydrogen acceptor and a coupling group, and water is the only byproduct. The reaction involves the reduction of nitro groups, C-H bond thioetherification, and C-H bond dehydroaromatization. This scheme offers broad synthetic value for further elaborations, as exemplified by a 3-step total synthesis of antipsychotic chlorpromazine.

Direct Synthesis of Esters from Alkylarenes and Carboxylic Acids: The C-H Bond Dehydroesterification.

Herein, a reaction in which the benzyl C-H bonds of alkylarenes are directly esterified by carboxylic acids to produce benzyl esters in high yields is reported. This reaction is catalyzed by Pd nanoparticles (NPs) on N-doped carbon (CN) composites based on a carbonizing Al-MIL-101(NH2) material, and no oxidants or hydrogen acceptors are required. Use of o-alkylbenzoic acids as substrates leads to phthalides, whereas with carboxylic acids and alkylarenes as the feedstock, the reaction produces the benzyl esters. These reactions that use readily available alkylarenes instead of benzyl halides or benzyl alcohols as raw materials for one-step synthesis of benzyl esters without oxidants are inherently atom- and step-efficient. The CN composites and the CN-supported Pd NP catalysts were prepared and are well characterized. The proposed mechanism involves dehydrogenation of both the carboxylic groups and the benzylic groups and the transformation of benzylic C-H bond into the C-O bond via hydrogen abstraction from the benzylic group through an organopalladium intermediate. The kinetic isotope effect (kH/kD = 2.77) indicated that C(sp3)-H bond cleavage of the alkane aromatics is the rate-determining step.

Characterization of a Lipase From the Silkworm Intestinal Bacterium Bacillus pumilus With Antiviral Activity Against Bombyx mori (Lepidoptera: Bombycidae) Nucleopolyhedrovirus In Vitro.

To investigate whether Bombyx mori Linnaeus (Lepidoptera: Bombycidae) intestinal microorganism play a role in the host defence system against viral pathogens, a lipase gene from the silkworm intestinal bacterium Bacillus pumilus SW41 was characterized, and antiviral activity of its protein against B. mori nucleopolyhedrovirus (BmNPV) was tested. The lipase gene has an open-reading frame of 648 bp, which encodes a 215-amino-acid enzyme with a 34-amino-acid signal peptide. The recombinant lipase (without signal peptide) was expressed and purified by using an Escherichia coli BL21 (DE3) expression system. The total enzyme activity of this recombinant lipase reached 277.40 U/mg at the optimum temperature of 25°C and optimum pH value of 8.0. The antiviral test showed that a relative high concentration of the recombinant lipase reduced BmNPV infectivity in vitro, which resulted in decreased viral DNA abundance and viral occlusion bodies. Besides, the preincubation method also suggested that the lipase probably directly acting on the budded virions. The results suggest that the lipase from intestinal bacterium B. pumilus SW41 is a potential antiviral factor for silkworm against BmNPV.

Transcriptomic analysis of two Beauveria bassiana strains grown on cuticle extracts of the silkworm uncovers their different metabolic response at early infection stage.

Beauveria bassiana is an important entomopathogenic fungus which not only widely distributes in the environment but also shows phenotypic diversity. However, the mechanism of pathogenic differences among natural B. bassiana strains has not been revealed at transcriptome-wide level. In the present study, in order to explore the mechanism, two B. bassiana strains with different pathogenicity were isolated from silkworms (Bombyx mori L.) and selected to analyze the gene expression of early stage by culturing on cuticle extracts of the silkworm and using RNA-sequencing technique. A total of 2108 up-regulated and 1115 down-regulated genes were identified in B. bassiana strain GXsk1011 (hyper-virulent strain) compared with B. bassiana strain GXtr1009 (hypo-virulent strain), respectively. The function categorization of differential expressed genes (DEGs) showed that most of them involved in metabolic process, biosynthesis of secondary metabolites, catalytic activity, and some involved in nutrition uptake, adhesion and host defense were also noted. Based on our data, distinct pathogenicity among different strains of B. bassiana may largely attribute to unique gene expression pattern which differed at very early infection process. Most of the genes involved in conidia adhesion, cuticle degradation and fungal growth were up-regulated in hyper-virulent B. bassiana strain GXsk1011. Furthermore, in combination with fungal growth analysis, our research provided a clue that fungal growth may also play an important role during early infection process. The results will help to explain why different B. bassiana strains show distinct pathogenicity on the same host even under same condition. Moreover, the transcriptome data were also useful for screening potential virulence factors.

Antiviral activity and specific modes of action of bacterial prodigiosin against Bombyx mori nucleopolyhedrovirus in vitro.

Prodigiosin, the tripyrrole red pigment, is a bacterial secondary metabolite with multiple bioactivities; however, the antiviral activity has not been reported yet. In the present study, we found the antiviral activity of bacterial prodigiosin on Bombyx mori nucleopolyhedrovirus (BmNPV)-infected cells in vitro, with specific modes of action. Prodigiosin at nontoxic concentrations selectively killed virus-infected cells, inhibited viral gene transcription, especially viral early gene ie-1, and prevented virus-mediated membrane fusion. Under prodigiosin treatment, both progeny virus production and viral DNA replication were significantly inhibited. Fluorescent assays showed that prodigiosin predominantly located in cytoplasm which suggested it might interact with cytoplasm factors to inhibit virus replication. In conclusion, the present study clearly indicates that prodigiosin possesses significant antiviral activity against BmNPV.

Silica-based 2-(N,N-dimethylamino)-1,3-propanediol hydrophilic interaction liquid chromatography stationary phase for separating cephalosporins and carbapenems.

A silica-based stationary phase bearing both hydrophilic hydroxyl and amino groups was developed by covalently bonding a small molecular N,N-dimethylamino 1,3-propanediol moiety onto silica beads via copper(I)-catalyzed Huisgen azide-alkyne 1,3-dipolar cycloaddition (CuAAC). This new stationary phase showed good HILIC characteristics and high column efficiency (the theoretical plate number is up to 37000 plates m(-1) in the case of inosine) in the separation of polar compounds, such as nucleosides and bases, organic acids, cephalosporins, and carbapenems.

Palladium-catalyzed dehydrogenation of α-cyclohexene-substituted nitriles to α-aryl nitriles.

The development of a practical, inexpensive, and cyanide-free method for synthesizing α-aryl nitriles remains a challenging goal in synthetic chemistry. Here, we report an approach for synthesizing α-aryl nitriles toward achieving this goal, by which α-cyclohexenyl acetonitriles and α-cyclohexenyl alkenyl nitriles are dehydrogenated to α-aryl nitriles.

NLRP3 inflammasome-mediated premature immunosenescence drives diabetic vascular aging dependent on the induction of perivascular adipose tissue dysfunction.

AIMS: The vascular aging process accelerated by type 2 diabetes mellitus (T2DM) is responsible for the elevated risk of associated cardiovascular diseases (CVDs). Metabolic disorder-induced immune senescence has been implicated in multi-organ/tissue damage. Herein, we sought to determine the role of immunosenescence in diabetic vascular aging and to investigate the underlying mechanisms. METHODS AND RESULTS: Aging hallmarks of the immune system appear prior to the vasculature in streptozotocin (STZ)/high-fat diet (HFD)-induced T2DM mice or db/db mice. Transplantation of aged splenocytes or diabetic splenocytes into young mice triggered vascular senescence and injury compared to normal control splenocyte transfer. RNA-seq profile and validation in immune tissues revealed that the Toll-like receptor 4 (TLR4)- Nuclear factor-kappa B (NF-κB) -NLRP3 axis might be the mediator of diabetic premature immunosenescence. The absence of Nlrp3 attenuated immune senescence and vascular aging during T2DM. Importantly, senescent immune cells, particularly T cells, provoked perivascular adipose tissue (PVAT) dysfunction and alternations in its secretome, which in turn impair vascular biology. In addition, senescent immune cells may uniquely affect vasoconstriction via influencing PVAT. Lastly, rapamycin alleviated diabetic immune senescence and vascular aging, which may be partly due to NLRP3 signaling inhibition. CONCLUSION: These results indicated that NLRP3 inflammasome-mediated immunosenescence precedes and drives diabetic vascular aging. The contribution of senescent immune cells to vascular aging is a combined effect of their direct effects and induction of PVAT dysfunction, the latter of which can uniquely affect vasoconstriction. We further demonstrated that infiltration of senescent T cells in PVAT was increased and associated with PVAT secretome alterations. Our findings suggest that blocking the NLRP3 pathway may prevent early immunosenescence and thus mitigate diabetic vascular aging and damage, and targeting senescent T cells or PVAT might also be the potential therapeutic approach.

Formation of C=N bonds by the release of H2: a new strategy for synthesis of imines and benzazoles.

A new strategy for synthesis of imines using the approach of release of H2 has been developed. This oxidant- and acceptor-free Pd/C catalysis protocol is further applied to synthesis of benzoxazoles, benzimidazoles, and benzothiazoles through a one-pot cascade reaction with notably high yields.

Application of click chemistry on preparation of separation materials for liquid chromatography.

With the increasing requirement for analysis and separation of samples related to genomics, proteomics, metabolomics, pharmacology and agrochemistry, diverse stationary phases for liquid chromatography have been prepared by Cu(i)-catalyzed 1, 3-dipolar azide-alkyne cycloaddition reaction (CuAAC). It has been proved that CuAAC is a powerful tool for preparing covalently bonded stationary phases. In this tutorial review, we highlighted the preparation of separation materials by immobilization of functional groups on silica beads, polymer beads and agarose via CuAAC and their applications in liquid chromatography and related purposes, such as separation of polar compounds, enrichment of valuable bio-samples, orthogonal two-dimensional HPLC and chiral separation. Meanwhile, agarose-based separation materials for affinity chromatography are reviewed.

Selective Oxidation of Alkylarenes to the Aromatic Ketones or Benzaldehydes with Water.

Here a palladium-catalyzed oxidation method for converting alkylarenes into the aromatic ketones or benzaldehydes with water as the only oxygen donor is reported. This C-H bond oxidation functionalization does not require other oxidants and hydrogen acceptors, and H2 is the only byproduct. The oxygen atom introduced into the products is confirmed to be from water by the MS analysis on the product of the 18O-labeled water reaction.

Transition-metal-free highly efficient aerobic oxidation of sulfides to sulfoxides under mild conditions.

A highly efficient transition-metal-free catalytic system Br2/NaNO2/H2O has been developed for a robust and economic acid-free aerobic oxidation of sulfides. It is noteworthy that the sulfide function reacts under mild conditions without over-oxidation to sulfone. The role of NaNO2as an efficient NO equivalent for the activation of molecular oxygen was identified. Under the optimal conditions, a broad range of sulfide substrates were converted into their corresponding sulfoxides in high yields by molecular oxygen. The present catalytic system utilizes cheap and readily available agents as the catalysts, exhibits high selectivity for sulfoxide products and releases only innocuous water as the by-products.

Naphtho[2,3-b]furan-4,9-dione synthesis via palladium-catalyzed reverse hydrogenolysis.

A reverse hydrogenolysis process has been developed for two-site coupling of 2-hydroxy-1,4-naphthoquinones with olefins to produce naphtha[2,3-b]furan-4,9-diones and hydrogen (H2). The reaction is catalyzed by commercially available Pd/C without oxidants and hydrogen acceptors, thereby providing an intrinsically waste-free approach for the synthesis of functionalized and potentially biologically relevant naphtha[2,3-b]furan-4,9-diones.

NaNO(2)/FeCl(3) catalyzed wet oxidation of the azo dye Acid Orange 7.

A combination of ferric chloride and sodium nitrite significantly improved the wet oxidation of the azo dye Acid Orange 7 (AO7) in acid aqueous media (pH 2.6) under moderate conditions (T=150 degrees C; oxygen pressure=0.5 MPa). To evaluate the catalytic system, wet oxidation of AO7 was carried out at temperatures between 90 and 150 degrees C and oxygen pressures ranging from 0.1 to 0.5 MPa. The effect of initial solution pH from 2.6 to 11.4 and the amount of catalyst on the degradation of AO7 were also investigated. AO7 initial concentration was kept 200 mg L(-1). The degradation process was monitored by UV-visible spectroscopy, HPLC, IC (ion chromatography), GC-MS and TOC analysis. At 150 degrees C and 0.5 MPa oxygen pressure, 56% TOC was removed after 4h of treatment, while no obvious TOC removal were achieved without catalyst at the same experimental condition. The main degradation products were some small organic acids: formic acid, acetic acid, pyruvic acid, oxalic acid, succinic acid (identified and quantified by IC) and phthalic acid (identified by GC-MS).

Pd/C-catalyzed dehydrogenation of 2-cinnamoylbenzoic acids to 3-benzylidene-3H-isochroman-1,4-diones.

Pd/C, a widely accepted hydrogenation catalyst, is found to catalytically dehydrogenate 2-cinnamoylbenzoic acids to 3-benzylidene-3-H-isochroman-1,4-diones with H2 as the only byproduct. This synthetic reaction proceeds without oxidants and hydrogen acceptors, thereby representing an atom- and step-efficient approach to a wide range of functionalized 3-benzylidene-3H-isochroman-1,4-diones.

C-H Functionalization via Remote Hydride Elimination: Palladium Catalyzed Dehydrogenation of ortho-Acyl Phenols to Flavonoids.

Although deprotonation of electron-poor C-H bonds to carbon anions with bases has long been known and widely used in organic synthesis, the hydride elimination from electron-rich C-H bonds to carbon cations or partial carbocations for the introduction of nucleophiles is a comparatively less explored area. Here we report that the carbonyl ß-C(sp3)-H bond hydrogens of ortho-acyl phenols could be substituted by intramolecular phenolic hydroxyls to form O-heterocycles, followed by dehydrogenation of the O-heterocycle into flavonoids. The cascade reaction is catalyzed by Pd/C without added oxidants and sacrificing hydrogen acceptors.

NaNO2-activated, iron-TEMPO catalyst system for aerobic alcohol oxidation under mild conditions.

FeCl3-TEMPO-NaNO2 catalyses the selective and mild aerobic oxidation of a broad range of alcohols to the corresponding aldehydes and ketones.

Click N-benzyl iminodiacetic acid: novel silica-based tridentate zwitterionic stationary phase for hydrophilic interaction liquid chromatography.

Iminodiacetic acid (IDA) is dicarboxylic acid amine, which may produce stronger interaction with polar or charged compounds than bidentate α,ß-amino acid. In this article, a novel type of tridentate zwitterionic HILIC stationary phase was prepared by covalently bonding N-benzyl IDA on silica gel via copper(I) catalyzed Huisgen azide-alkyne 1,3-dipolar cycloaddition (CuAAC). The structure of this stationary phase and all related intermediates was confirmed by NMR, FT-IR, MS spectrum and elemental analysis. The new stationary phase showed good HILIC characteristics and high column efficiency (the theoretical plate number is up to 44000 plates m(-1) in the case of guanosine) in the application of separation of polar compounds, including organic acids, organic bases, as well as highly polar and hydrophilic compounds, such as cephalosporins and carbapenems. Most of them displayed good peak shape and selectivity.

An efficient route to highly enantioenriched tetrahydroazulenes and ß-tetralones by desymmetrization reactions of δ,δ-diaryldiazoaceto-acetates.

A highly stereoselective desymmetrization reaction of δ,δ-diaryl-α-diazo-ß-ketoesters catalyzed by chiral dirhodium carboxylates forms aromatic cycloaddition products in up to 97% ee.

One-pot, three-component reaction using modified Julia reagents: a facile synthesis of 4,5-disubstituted 1,2,3-(NH)-triazoles in a wet organic solvent.

A new one-pot, three component reaction involving the use of Julia reagent, aldehyde, and sodium azide was developed for the efficient synthesis of N-unsubstituted 1,2,3-triazoles. This reaction could be carried out under mild reaction conditions without any precaution, and broad scope of substrates, both respect to Julia reagents and aldehydes, could be applied in this reaction system in generation of a small library of title compounds.