Salicylaldehyde as an SET-HAT Bifunctional Photocatalyst for the Intermolecular Transalkylation of Phthalimide.

Salicylaldehyde works as an efficient photocatalyst for the intermolecular transalkylation of phthalimide. The well-designed dimethyl N-hydroxyphthalimide ester proves to be a good alkylation reagent. It inhibits the competing intramolecular alkylation of alkylating reagent, enabling the site-specific synthesis of N-substituted phthalimide.

Transcriptomic and physiological analysis of the effect of octanoic acid on Meloidogyne incognita.

Root knot nematodes are the most devastating root pathogens, causing severe damage and serious economic losses to agriculture worldwide. Octanoic acid has been reported as one of the nematicides, and its mode of action is not fully understood. The main objective of this study was to elucidate the effect of octanoic acid on Meloidogyne incognita by transcriptomic analysis combined with physiological and biochemical assays. In the toxicity assays with octanoic acid, the threshold concentration with nematicidal activity and the maximum concentration to which nematodes could respond were 0.03 µL/mL and 0.08 µL/mL respectively. Microscopic observation combined with protein and carbohydrates assays confirmed that the structure of the second-stage juveniles (J2s) was severely disrupted after 72 h of immersion in octanoic acid. Transcriptome analysis has shown that octanoic acid can interfere with the nematode energy metabolism, lifespan and signaling. Although the effects are multifaceted, the findings strongly point to the cuticle, lysosomes, and extracellular regions and spaces as the primary targets for octanoic acid. In addition, nematodes can withstand the negative effects of low concentration of octanoic acid to some extent by up-regulating the defense enzyme system and heterologous metabolic pathways. These findings will help us to explore the nematicidal mechanism of octanoic acid and provide important target genes for the development of new nematicides in the future.

Iridium-Catalyzed Asymmetric Allylic Substitution Reactions.

In this review, we summarize the origin and advancements of iridium-catalyzed asymmetric allylic substitution reactions during the past two decades. Since the first report in 1997, Ir-catalyzed asymmetric allylic substitution reactions have attracted intense attention due to their exceptionally high regio- and enantioselectivities. Ir-catalyzed asymmetric allylic substitution reactions have been significantly developed in recent years in many respects, including ligand development, mechanistic understanding, substrate scope, and application in the synthesis of complex functional molecules. In this review, an explicit outline of ligands, mechanism, scope of nucleophiles, and applications is presented.

Discovery of Oxygen α-Nucleophilic Addition to α,ß-Unsaturated Amides Catalyzed by Redox-Neutral Organic Photoreductant.

The conjugate additions of oxygen-centered nucleophiles to conjugate acceptors are among the most powerful C-O bond formation reactions. The conjugate addition normally takes place at the ß-position carbon to the electron-withdrawing group, resulting in the formation of a stabilized carbanion intermediate that can be quenched by proton or electrophiles to form the ß-addition (i.e., hetero-Michael addition) products. On the contrary, the formation of α-hydroxyl or alkoxyl amides through conjugate addition needs an α,ß-inverse addition. Nevertheless, a regio-inversed nucleophilic α-addition of oxygen-centered nucleophiles to α,ß-unsaturated carbonyl compounds still remains less explored because of the electronic mismatch. In this research, we discovered the first α-specific nucleophilic addition of α,ß-unsaturated amides with oxygen and fluoride nucleophiles. This region-inversed nucleophilic addition is enabled by the catalysis of a novel redox-neutral nondonor-acceptor organic photoreductant (CBZ6). As low as 0.5 mol % of visible light photoreductant was employed. The mechanistic insights were also explored. The oxidative potential of the excited state of CBZ6 is obtained in -1.92 V (vs SCE), presenting a stronger reductive potential than representative metal-cored or organic photoredox catalysts. This feature enabled the umpolung of α,ß-unsaturated amides to take place α-nucleophilic addition other than the normal ß-addition.

Deprotonated Salicylaldehyde as Visible Light Photocatalyst.

Salicylaldehyde is established as an efficient visible light photocatalyst for the first time. Compared to other simple aldehyde analogies, salicylaldehyde has a unique deprotonative red-shift from 324 to 417 nm and gives rise to the remarkable increase of fluorescence quantum from 0.0368 to 0.4632, thus enabling salicylaldehyde as a visible light (>400 nm) photocatalyst. The experimental investigations suggest that the reactive radical species are generated by sensitization of the substrates by the deprotonated salicylaldehyde through an energy-transfer pathway. Consequently, the C-C cleaving alkylation reactions of N-hydroxyphthalimide esters proceed smoothly in the presence of as low as 1 mol % of salicylaldehyde under the visible-light irradiation, affording desired alkylation products with up to 99% yields. Application in visible-light induced aerobic oxidation of N-alkylpyridinium salts is also reported.

Overcoming Electron-Withdrawing and Product-Inhibition Effects by Organocatalytic Aerobic Oxidation of Alkylpyridines and Related Alkylheteroarenes to Ketones.

An organocatalyzed aerobic benzylic C-H oxidation of alkyl and aryl heterocycles has been developed. This transition metal-free method is able to overcome the electron-withdrawing effect as well as product-inhibition effects in heterobenzylic radical oxidation. A variety of ketones bearing N-heterocyclic groups could be prepared under relatively mild conditions with moderate to high yields.

Radical α,ß-Dehydrogenation of Saturated Amides via α-Oxidation with TEMPO under Transition Metal-Free Conditions.

A transition metal-free radical process for the selective α,ß-dehydrogenation of saturated amides under mild conditions is developed. Utilizing radical activation strategy, the challenging issue associated with the low α-acidity of amides is resolved. For the first time, α,ß-unsaturated Weinreb amides and acrylamides could be efficiently prepared directly from corresponding saturated amides. Mechanistic studies confirm the radical nature of this transformation. Two gram scale α,ß-dehydrogenation have also been performed to demonstrate the utility of this method.

Competing Dehalogenation versus Borylation of Aryl Iodides and Bromides under Transition-Metal-Free Basic Conditions.

In this work, selectivity-controllable base-promoted transition-metal-free borylation and dehalogenation of aryl halides are described. Under the conditions of borylation, the dehalogenation which emerges as a competitive side reaction has been well-controlled by carefully controlling the borylation conditions. On the other hand, the dehalogenation using benzaldehyde as a hydrogen source has also been accomplished. The applications of direct radical borylation and dehalogenation of aryl halides demonstrate their synthetic practicability in pharmaceutical-oriented organic synthesis. Based on the experimental evidences, the tBuOK/1,10-Phen-triggered radical nature of both competitive reactions has been revealed.

Cleavage of C(aryl)-CH3 Bonds in the Absence of Directing Groups under Transition Metal Free Conditions.

Organic chemists now can construct carbon-carbon σ-bonds selectively and sequentially, whereas methods for the selective cleavage of carbon-carbon σ-bonds, especially for unreactive hydrocarbons, remain limited. Activation by ring strain, directing groups, or in the presence of a carbonyl or a cyano group is usually required. In this work, by using a sequential strategy site-selective cleavage and borylation of C(aryl)-CH3 bonds has been developed under directing group free and transition metal free conditions. Methyl groups of various arenes are selectively cleaved and replaced by boryl groups. Mechanistic analysis suggests that it proceeds by a sequential intermolecular oxidation and coupling of a transient aryl radical, generated by radical decarboxylation, involving a pyridine-stabilized persistent boryl radical.

Direct Wittig Olefination of Alcohols.

A base-promoted transition metal-free approach to substituted alkenes using alcohols under aerobic conditions using air as the inexpensive and clean oxidant is described. Aldehydes are relatively difficult to handle compared to corresponding alcohols due to their volatility and penchant to polymerize and autoxidize. Wittig ylides are easily oxidized to aldehydes and consequently form homo-olefination products. By the strategy of simultaneously in situ generation of ylides and aldehydes, for the first time, alcohols are directly transferred to olefins with no need of prepreparation of either aldehydes or ylides. Thus, the di/monocontrollable olefination of diols is accomplished. This synthetically practical method has been applied in the gram-scale synthesis of pharmaceuticals, such as DMU-212 and resveratrol from alcohols.

Synthesis of Functionalized Indoles via Palladium-Catalyzed Aerobic Cycloisomerization of o-Allylanilines Using Organic Redox Cocatalyst.

A scalable and practical synthesis of functionalized indoles via Pd- tBuONO cocatalyzed aerobic cycloisomerization of o-allylanilines is reported. Using molecular oxygen as a terminal oxidant, a series of substituted indoles were prepared in moderate to good yields. The avoidance of hazardous oxidants, heavy-metal cocatalysts, and high boiling point solvents such as DMF and DMSO enables this method to be applied in pharmaceutical synthesis. A practical gram-scale synthesis of indomethacin demonstrates its application potential.

Tuning Regioselectivity of Wacker Oxidation in One Catalytic System: Small Change Makes Big Step.

A regioselectivity switchable aerobic Wacker-Tsuji oxidation has been developed using catalytic tert-butyl nitrite as a simple organic redox cocatalyst. By solely switching the solvent, either substituted aldehydes or ketones could be prepared under mild aerobic conditions in good yields, respectively. A mechanistic explanation for the selectivity control is proposed.

Synthesis of Highly Functionalized Indoles and Indolones via Selectivity-Switchable Olefinations.

Highly functionalized indoles and indolones were prepared via selectivity-switchable mono- or diolefinations. The Julia olefination of the products followed by a Brønsted acid-prompted cyclization afforded indolones, whereas the indoles were obtained by a sequential Wittig olefination and electrocyclization. This method opens divergent access to highly functionalized nitrogen-containing bicyclic or tricyclic heterocycles.

The effects of avermectin on amino acid neurotransmitters and their receptors in the pigeon brain.

The objective of this study was to examine the effects of avermectin (AVM) on amino acid neurotransmitters and their receptors in the pigeon brain. Four groups two-month-old American king pigeons (n=20/group) were fed either a commercial diet or an AVM-supplemented diet (20mg/kg·diet, 40 mg/kg·diet, or 60 mg/kg·diet) for 30, 60, or 90 days. The contents of aspartic acid (ASP), glutamate (GLU), glycine (GLY), and γ-aminobutyric acid (GABA) in the brain tissues were determined using ultraviolet high-performance liquid chromatography (HPLC). The expression levels of the GLU and GABA receptor genes were analyzed using real-time quantitative polymerase chain reaction (qPCR). The results indicate that AVM exposure significantly enhances the contents of GABA, GLY, GLU, and ASP in the cerebrum, cerebellum, and optic lobe. In addition, AVM exposure increases the mRNA expression levels of γ-aminobutyric acid type A receptor (GABAAR), γ-aminobutyric acid type B receptor (GABABR), N-methyl-d-aspartate 1 receptor (NR1), N-methyl-d-aspartate 2A receptor (NR2A), and N-methyl-d-aspartate 2B receptor (NR2B) in a dose- and time-dependent manner. Moreover, we found that the most damaged organ was the cerebrum, followed by the cerebellum, and then the optic lobe. These results show that the AVM-induced neurotoxicity may be associated with its effects on amino acid neurotransmitters and their receptors. The information presented in this study will help supplement the available data for future AVM toxicity studies.

Synthesis Enabled by E-to-Z Isomerization Using CBZ6 as Energy Transfer Photocatalyst.

The reactions of Z-isomers and E-isomers usually are different in consideration of the regioselectivity of chemoselectivity. The syntheses of Z-isomers are not feasible in many cases. The energy transfer (EnT) E/Z-photoisomerization might yield the Z-isomers. In this work, CBZ6 was proven to be an EnT photocatalyst for the E → Z-isomerization of C-C or C-N double bonds. The transformations of in situ generated Z-isomers of oximes and stilbenes consequently afforded the desired reversed Beckmann rearrangement products and phenanthrenes, respectively.

Avermectin induced liver injury in pigeon: mechanisms of apoptosis and oxidative stress.

Extensive use of avermectin (AVM) can result in environment pollution, and it is important to evaluate the potential impact this antibiotic has on ecological systems. Few published literatures have discussed the liver injury mechanisms induced by AVM on birds. In this study, pigeons were exposed to feed containing AVM (0, 20, 40 and 60 mg/kg diet) for 30, 60, 90 days respectively. The results showed that AVM increased the number of apoptosis and the expression level of caspase-3, 8, fas mRNA in the liver of pigeons. Ultrastructural alterations, including mitochondrial damage and chromatin aggregation, become severe with increase exposure dose. Exposure to AVM induced significant changes in antioxidant enzyme {superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)} activities and malondialdehyde (MDA) content, augmented protein carbonyl (PCO) content and DNA-protein crosslink (DPC) coefficient, in a concentration-dependent manner in the liver of pigeons. Our results show that AVM has toxic effect in pigeon liver, and the mechanism of injury caused by AVM is closely related to apoptosis and oxidative stress.

Effect of atrazine and chlorpyrifos exposure on cytochrome P450 contents and enzyme activities in common carp gills.

Chlorpyrifos (CPF) and atrazine (ATR) are the most widely used organophosphate insecticides and triazine herbicides, respectively, worldwide. This study aimed at investigating the effects of ATR, CPF and mixture on common carp gills following 40-d exposure and 40-d recovery experiments. Cytochrome P450 content, activities of aminopyrine N-demethylase (APND) and erythromycin N-demethylase (ERND) and the mRNA levels of the CYP1 family (CYP1A, CYP1B, and CYP1C) were determined. In total, 220 common carps were divided into eleven groups, and each group was treated with a specific concentration of ATR (4.28, 42.8 and 428 µg/L), CPF (1.16, 11.6 and 116 µg/L) or ATR-CPF mixture (1.13, 11.3 and 113 µg/L). The results showed that P450 content and activities of APND and ERND in fish exposed to ATR and mixture were significantly higher than those in the control group. After the 40-d recovery treatment (i.e., depuration), the P450 content and the activities of APND and ERND in fish decreased to the background levels. A similar tendency was also found in the mRNA levels of the CYP1 family (CYP1A, CYP1B, and CYP1C) in common carp gills. The CPF-treated fish showed no significant difference from the control groups, except for a significant CYP1C induction. These results indicated that CYP enzyme levels are induced by ATR but were only slightly affected by CPF in common carp gills. In addition, the ATR and CPF exposure showed an antagonistic effect on P450 enzymes in common carp gills.

Antioxidant response and histopathological changes in brain tissue of pigeon exposed to avermectin.

Avermectins (AVMs) are the active components of some insecticidal and nematicidal products used in agriculture and veterinary medicine for the prevention of parasitic diseases. Residues of AVM drugs or their metabolites in livestock feces have toxic effects on non-target aquatic and terrestrial organisms. In this study, oxidative stress responses and pathological changes on pigeon brain tissues and serum after subchronic exposure to AVM for 30, 60 and 90 days were investigated. The decrease in antioxidant enzyme (superoxide dismutase, SOD and glutathione peroxidase, GSH-Px) activities and increase in methane dicarboxylic aldehyde content in a dose-time-dependent manner in the brain and serum of pigeon were observed. The protein carbonyl content, an indicator of protein oxidation, and DNA-protein crosslink coefficient were significantly augmented with dose-time-dependent properties. The microscopic structures of the cerebrum, cerebellum and optic lobe altered obviously, the severity of which increased with the concentration of AVM and exposure time. The results imply that AVM could induce oxidative damage to the brain tissue and serum of pigeon. The information presented in this study is helpful to understand the mechanism of AVM-induced oxidative stress in birds.

Photocatalytic Redox-Neutral Alkoxyacylation of Alkenes.

ß-Alkoxyketones are important building blocks in organic synthesis. By utilizing CBZ6, with an oxidative potential of -2.16 V (vs the saturated calomel electrode), as a redox-neutral photocatalyst, alkoxyacylation of olefins was accomplished under the irradiation of visible light via a cationic intermediate. It involves the addition of an acyl radical to olefin to form a radical intermediate and the following oxidation of the radical intermediate to the benzyl cationic intermediate that is captured by alkoxy anions. This process provides concise and practical access to the ß-functionalized ketones.

Reductive Cleavage of C-X or N-S Bonds Catalyzed by Super Organoreductant CBZ6.

The reductive cleavage of C(Ar)-X bonds is the key step for the cross coupling of Ar-X with other groups. In this work, under the irradiation of 407 nm LEDs using sodium formate as reductant and thiol as hydrogen atom transfer agent, a variety of (hetero)aryl chlorides, bromides, and iodides could be reduced to corresponding (hetero)arenes. The key intermediates, aryl radicals, could be trapped by either hydrogen, phosphite, or borates. The same reduction conditions can be extended to the deprotection of sulfonamides.