[3 + 2] Cycloaddition Reaction of Vinylsulfonium Salts with Hydrazonoyl Halides: Synthesis of Pyrazoles.

An efficient [3 + 2] cycloaddition reaction between in situ generated nitrile imines from hydrazonoyl halides and vinylsulfonium salts is developed. The nitrile imines are demonstrated to be a new class of reaction partner for vinylsulfonium salts to conduct the [3 + 2] cycloaddition reaction. The process provides a concise and efficient method for the construction of pyrazole derivatives under mild reaction conditions with broad substrate scope, good product yields, and high regioselectivity.

Synthesis of difluoromethylated spiropyrazolones via [3 + 2] cycloaddition of difluoroacetohydrazonoyl bromides with alkylidene pyrazolones.

An effective [3 + 2] cycloaddition reaction of difluoromethyl or trifluoromethyl hydrazonoyl bromides with alkylidene pyrazolones was disclosed. This method provides an efficient approach for accessing a variety of highly functionalized fluoroalkyl spiropyrazolones in good yields. This protocol also features some advantages such as easily available and stable substrates, simple operation procedures, and atom and step economy. The formation of (cis)- and (trans)-products was discussed.

Tandem Addition/Cyclization/Halogenation Reaction of Difluoromethylated N-Acylhydrazones with Allyltrimethylsilanes.

As novel difluoromethyl building blocks, difluoromethylated N-acylhydrazones react with allyltrimethylsilanes and the halogen source via a tandem addition/cyclization/halogenation strategy, which produces various difluoromethylpyrazoline compounds in good yields. The method features mild reaction conditions, broad substrate scopes, and a transition metal-free process with easy operation. It also proves that difluoromethylated N-acylhydrazones are useful difluoromethyl building blocks for the construction of difluoromethylated nitrogen heterocycles.

The cyclization/rearrangement of α-hydroxy ketones with trifluoromethyl N-acylhydrazones to synthesize multi-substituted trifluoromethyloxazolines.

A highly efficient and metal-free [3+2] cyclization/rearrangement reaction toward the synthesis of multisubstituted trifluoromethyloxazolines from α-hydroxyketones and trifluoromethyl N-acylhydrazones has been developed. The unprecedented rearrangement of the amide fragment under acidic conditions after cleavage of the N-N bond of acylhydrazones has opened up new avenues for the development of reactions involving trifluoromethyl N-acylhydrazones. DFT calculations show that the mechanism involves multiple proton transfer processes.

Visible-Light-Induced Four-Component Ritter-Type Reaction: Access to ß-Trifluoromethyl Imides.

A visible-light-induced four-component Ritter-type reaction was developed for the synthesis of ß-trifluoromethyl imides from CF3Br, alkenes, carboxylic acids, and nitriles. This protocol features mild reaction conditions, a broad substrate scope, and excellent functional group compatibility. Furthermore, this method has been proven to be suitable for the late-stage diversification of drug molecules. A mechanism involving a Ritter-type reaction and Mumm rearrangement was proposed on the basis of the control experiments.

Visible Light Promotes Cascade Trifluoromethylation/Cyclization, Leading to Trifluoromethylated Polycyclic Quinazolinones, Benzimidazoles and Indoles.

Efficient visible-light-induced radical cascade trifluoromethylation/cyclization of inactivated alkenes with CF3Br, which is a nonhygroscopic, noncorrosive, cheap and industrially abundant chemical, was developed in this work, producing trifluoromethyl polycyclic quinazolinones, benzimidazoles and indoles under mild reaction conditions. The method features wide functional group compatibility and a broad substrate scope, offering a facile strategy to pharmaceutically produce valuable CF3-containing polycyclic aza-heterocycles.

Photoinduced Trifluoromethylation with CF3Br as a Trifluoromethyl Source: Synthesis of α-CF3-Substituted Ketones.

An efficient and novel photoinduced trifluoromethylation employing CF3Br as a trifluoromethyl source is described. With commercially accessible fac-Ir(III)(ppy)3 as the catalyst, radical trifluoromethylation between O-silyl enol ether and CF3Br occurs successfully. This method provides various α-CF3-substituted ketones with a broad substrate scope in good yields under mild reaction conditions.

Synthesis of 3-Trifluoromethyl-1,2,4-triazolines and 1,2,4-Triazoles via Tandem Addition/Cyclization of Trifluoromethyl N-Acylhydrazones with Cyanamide.

A tandem addition/cyclization reaction between trifluoromethyl N-acylhydrazones and cyanamide is described, which provides a novel and efficient process for the synthesis of polysubstituted 3-trifluoromethyl-1,2,4-triazolines and their derivatives. The method has the advantages of mild reaction conditions, a broad substrate scope, good product yields, and atom economy.

Synthesis of Difluoromethylated Pyrazoles by the [3 + 2] Cycloaddition Reaction of Difluoroacetohydrazonoyl Bromides.

As novel and efficient difluoromethyl building blocks, difluoroacetohydrazonoyl bromides have been synthesized for the first time. The synthetic utility of this reagent for the construction of difluoromethyl organic compounds is demonstrated by their effective regioselective [3 + 2] cycloaddition reactions with ynones, alkynoates, and ynamides. The reactions provide a novel and efficient protocol to access difluoromethyl-substituted pyrazoles in good to excellent yields.

Synthesis of CF3-Substituted 1,6-Dihydropyridazines by Copper-Promoted Cascade Oxidation/Cyclization of Trifluoromethylated Homoallylic N-Acylhydrazines.

A highly efficient strategy for the construction of CF3-substituted 1,6-dihydropyridazines has been developed by cascade oxidation/cyclization of trifluoromethylated N-acylhydrazines. The produced 1,6-dihydropyridazines could be easily transformed to 3-trifluoromethyl pyridazine derivatives. Some of the 1,6-dihydropyridazines exhibited aggregation-induced emission (AIE). DFT calculations were conducted to explain the mechanism.

Sesamin induces A549 cell mitophagy and mitochondrial apoptosis via a reactive oxygen species-mediated reduction in mitochondrial membrane potential.

Sesamin, a lipid-soluble lignin originally isolated from sesame seeds, which induces cancer cell apoptosis and autophagy. In the present study, has been reported that sesamin induces apoptosis via several pathways in human lung cancer cells. However, whether mitophagy is involved in sesamin induced lung cancer cell apotosis remains unclear. This study, the anticancer activity of sesamin in lung cancer was studied by reactive oxygen species (ROS) and mitophagy. A549 cells were treated with sesamin, and cell viability, migration ability, and cell cycle were assessed using the CCK8 assay, scratch-wound test, and flow cytometry, respectively. ROS levels, mitochondrial membrane potential, and apoptosis were examined by flow cytometric detection of DCFH-DA fluorescence and by using JC-1 and TUNEL assays. The results indicated that sesamin treatment inhibited the cell viability and migration ability of A549 cells and induced G0/G1 phase arrest. Furthermore, sesamin induced an increase in ROS levels, a reduction in mitochondrial membrane potential, and apoptosis accompanied by an increase in cleaved caspase-3 and cleaved caspase-9. Additionally, sesamin triggered mitophagy and increased the expression of PINK1 and translocation of Parkin from the cytoplasm to the mitochondria. However, the antioxidant N-acetyl-L-cysteine clearly reduced the oxidative stress and mitophagy induced by sesamin. Furthermore, we found that cyclosporine A (an inhibitor of mitophagy) decreased the inhibitory effect of sesamin on A549 cell viability. Collectively, our data indicate that sesamin exerts lethal effects on lung cancer cells through the induction of ROS-mediated mitophagy and mitochondrial apoptosis.

Diastereoselective synthesis of spiro-cyclopropanyl-cyclohexadienones via direct sulfide-catalyzed [2 + 1] annulation of para-quinone methides with bromides.

An efficient sulfide-catalyzed [2 + 1] annulation of para-quinone methides (p-QMs) with diverse bromides has been achieved. This catalytic strategy provides an efficient and straightforward protocol for accessing a variety of spiro-cyclopropanyl-cyclohexadienone compounds in good to excellent yields (64% to 96% yields) with outstanding diastereoselectivities (>20 : 1 dr), displaying good functional group tolerance as well as gram-scale capacity.

Visible-light-promoted acyl radical cascade reaction for accessing acylated isoquinoline-1,3(2H,4H)-dione derivatives.

A visible-light-promoted decarboxylative acyl radical acylation/cyclization cascade reaction of N-methacryloylbenzamides for accessing acylated isoquinoline-1,3(2H,4H)-dione derivatives was described. In this report, α-keto acids were used for generating acyl radicals and inducing radical acylations. This protocol features mild reaction conditions, operational practicality and a broad substrate scope.

Synthesis of Polysubstituted Trifluoromethylpyridines from Trifluoromethyl-α,ß-ynones.

A novel and efficient method for synthesis of polysubstituted trifluoromethylpyridine derivatives by the Bohlmann-Rahtz heteroannulation reaction is described, which use trifluoromethyl-α,ß-ynones as trifluoromethyl building blocks to react with ß-enamino esters or ß-enamino ketones in the presence of ZnBr2 to form the trifluoromethylpyridine derivatives in good yields. The protocol has the advantages of readily available starting materials, mild reaction conditions, and high atom economy.

Prognostic value of maximum standard uptake value, metabolic tumor volume, and total lesion glycolysis of positron emission tomography/computed tomography in patients with breast cancer: A systematic review and meta-analysis.

PURPOSE: A comprehensive systematic review of the literature was conducted on parameters from 18 F-FDG PET and a meta-analysis of the prognostic value of the maximal standard uptake value (SUVmax), metabolic tumor volume (MTV) and total lesional glycolysis (TLG) in patients with breast cancer (BC). PATIENTS AND METHODS: Relevant English articles from PubMed, EMBASE, and the Cochrane Library were retrieved. Pooled hazard ratios (HRs) were used to assess the prognostic value of SUVmax, MTV, and TLG. RESULTS: A total of 20 primary studies with 3115 patients with BC were included. The combined HRs (95% confidence interval [CI] of higher SUVmax and higher TLG for event-free survival (EFS) were 1.53 (95% CI, 1.25-1.89, P = 0.0006) and 5.94 (95% CI, 2.57-13.71, P = 0.97), respectively. Regarding the overall survival (OS), the combined HRs were 1.22 (95%CI, 1.02-1.45, P = 0.0006) with higher SUVmax, and 2.91(95% CI, 1.75-4.85, P = 0.44) with higher MTV. Higher MTV showed no correlation with EFS [1.31(95% CI, 0.65-2.65, P = 0.18)] and similarly higher TLG showed no correlation with OS [1.20(95% CI, 0.65-2.23, P = 0.45)]. Subgroup analysis showed that SUVmax, with a median value of 5.55 was considered as a significant risk factor for both EFS and OS in BC patients. CONCLUSION: Despite clinically heterogeneous BC patients and adoption of various methods between studies, the present meta-analysis results confirmed that patients with high SUVmax are at high risk of adverse events or death in BC patients, high MTV predicted a high risk of death and high TLG predicted a high risk of adverse events.

Visible-light induced decarboxylative alkylation of quinoxalin-2(1H)-ones at the C3-position.

A simple and efficient method for the visible light induced direct carbon alkylation of quinoxalin-2(1H)-ones at the C3 position is described. This protocol employs cheap and readily available phenyliodine(iii) dicarboxylates as the alkylation reagents to conduct decarboxylative radical coupling reaction with quinoxalin-2(1H)-ones. The process exhibits excellent compatibility to functional groups and provides a convenient and selective access to various 3-alkylquinoxalin-2(1H)-ones in good yields.

Tin Powder-Promoted Cascade Condensation/Allylation/Lactamization: Synthesis of Isoindolinones and Pyrazoloisoindol-8-ones.

An efficient tin powder-promoted cascade condensation/allylation/lactamization of 2-formylbenzoic acids, hydrazides, and allyl bromides was developed for the synthesis of isoindolinones in good to excellent yields under mild conditions without any other additives or catalysts. Further manipulation of isoindolinones by iodocyclization process afforded the tricyclic tetrahydro-8 H-pyrazolo[5,1- a]isoindol-8-one derivatives, which could be converted into more complicated tetracyclic tetrahydro-4 H-azirino[1',2':2,3]pyrazolo[5,1- a]isoindol-4-ones.

[3 + 2] Cycloaddition of para-Quinone Methides with Nitrile Imines: Approach to Spiro-pyrazoline-cyclohexadienones.

[3 + 2] cycloaddition of para-quinone methides with nitrile imines under mild conditions has been achieved. The corresponding spiro-pyrazoline-cyclohexadienone products were constructed in good to excellent yields (up to 97% yield) with high regioselectivity. This straightforward protocol exhibits good functional group tolerance and scalability and provides the spiro-pyrazoline-cyclohexadienones.

Electrochemical Radical Formyloxylation-Bromination, -Chlorination, and -Trifluoromethylation of Alkenes.

Given the versatility and value of the structurally diverse organohalides and CF3-containing compounds in organic synthesis, we reported a green, oxidant-free electrochemical method using undivided electrochemical cells for radical bromination, chlorination and trifluoromethylation-formyloxylation of the various alkenes with readily available halogen radical (NaCl, NaBr), trifluoromethyl radical (CF3SO2Na) sources, and DMF as formyloxylation reagents. The protocol is operationally simple and robust and the Cl-, Br- or CF3- was directly oxidized at the anode, obviating the need for exogenous chemical oxidants.

N-Arylations of trifluoromethylated N-acylhydrazones with diaryliodonium salts as arylation reagents.

A novel and efficient N-arylation of trifluoromethylated N-acylhydrazones is described by using diaryliodonium salts as arylation reagents in the presence of copper salts. A wide variety of N-aryl acylhydrazones are obtained with good to excellent yields under mild reaction conditions.