Visible-Light-Assisted Gold-Catalyzed Fluoroarylation of Allenoates.

A strategically novel synthetic method for the fluoroarylation of allenic ester was developed that enables the expedient construction of a host of ß-fluoroalkyl-containing cinnamate derivatives. The reaction proceeds through visible-light-promoted gold redox catalysis, occurs smoothly under very mild reaction conditions, accommodates a large variety of functional groups, and more importantly allows the incorporation of fluorine and aryl groups with excellent regio- and stereoselectivity. The concomitant activation mode for both the allene motif and the hydrogen fluoride is key for the success of the reaction.

Intermolecular Carboamination of Unactivated Alkenes.

Herein, we report the first example of group transfer radical addition of O-vinylhydroxylamine derivatives onto unactivated alkenes. By utilizing O-vinylhydroxylamine derivatives as both the N- and C-donors, this reaction enables intermolecular carboamination of unactivated alkenes in an atom economical fashion. As the process is initiated through N-radical addition followed by C-transfer, linear carboamination products are afforded. This differs from canonical radical carbofunctionalization of olefins, which typically favors branched product owing to initiation by C-radical addition.

Palladium-Catalyzed Fluoroarylation of gem-Difluoroalkenes.

A Pd-catalyzed fluoroarylation of gem-difluoroalkenes with aryl halides is reported. By taking advantage of the in situ generated α-CF3 -benzylsilver intermediates derived from the nucleophilic addition of silver fluoride to gem-difluoroalkenes, this strategy bypasses the use of a strong base, thus enabling a mild and general synthetic method for ready access to non-symmetric α,α-disubstituted trifluoroethane derivatives.

Multi-substituted trifluoromethyl alkene construction via gold-catalyzed fluoroarylation of gem-difluoroallenes.

An unprecedented fluoroarylation of 1,1-difluoroallenes with a cost-effective nucleophilic fluoride reagent and aryldiazonium salts is reported. This visible light promoted gold-catalyzed reaction allows a stereo- and regioselective incorporation of both the fluorine atom and aryl group, enabling a straightforward construction of multi-substituted trifluoromethyl alkenes. Under the mild reaction conditions, a nice tolerance of diverse functional groups is achieved. The high regioselectivity for fluorine-incorporation is rationalized by considering the thermodynamic driving force of trifluoromethyl group formation, whereas the counterintuitive stereoselectivity that aryl is installed on the side of the bulkier γ-substituent is interpreted by alleviating the increasing 1,3-allylic interaction in the gold-coordinated allene intermediate en route to the product.

Visible-Light-Induced Meerwein Fluoroarylation of Styrenes.

An unprecedented approach for assembling a broad range of 1,2-diarylethane derivatives with fluorine-containing fully substituted carbon centers was developed. The protocol features straightforward operation, proceeds under metal-free condition, and accommodates a large variety of synthetically useful functionalities. The critical aspect to the success of this novel transformation lies in using aryldiazonium salts as both aryl radical progenitor and also as single electron acceptor which elegantly enables a radical-polar crossover manifold.

MiR-139-5p/SLC7A11 inhibits the proliferation, invasion and metastasis of pancreatic carcinoma via PI3K/Akt signaling pathway.

OBJECTIVE: Pancreatic carcinoma (PANC) is one of the important aggressive cancers, with deficiency in effective therapeutics. The study aimed to investigate the effects and molecular mechanism of miR-139-5p/SLC7A11 on the proliferation and metastasis of PANC. METHODS: Bioinformatics was used to analyze the differentially expressed genes in the TCGA database. PANC cell lines with overexpressed miR-139-5p and Solute Carrier Family 7, Member 11 (SLC7A11) was established, and have been used to detect cell proliferation, invasion and metastasis of PANC Subsequently, bioinformatic analysis and dual luciferase reporter assay were performed to confirm that SLC7A11 was a target gene of miR-139-5p. Xenograft mice model was used to explore the functions of miR-139-5p in PANC tumorigenicity. RESULTS: MiR-139-5p could regulate and affect the protein expression of P13K and Akt associated with phosphatidylinositol signaling pathway by inhibiting SLC7A11. MiR-139-5p was found to be lowly expressed in PANC tissues, while SLC7A11 was highly expressed. Low expression of miR-139-5p and high expression of SLC7A11 were positively associated with poor clinical outcomes. PANC cell proliferation, invasion and metastasis could be inhibited by miR-139-5p overexpression and be promoted by SLC7A11 overexpression. MiR-139-5p overexpression could suppress PANC tumor growth and the expressions of SLC7A11, p-PI3K, p-Akt in tumor tissues. Therefore, the inhibitory of miR-139-5p to PANC cell proliferation, invasion and metastasis was partly due to its inhibiting effect on SLC7A11 expression. CONCLUSION: Our study proves that miR-139-5p/SLC7A11 has important functions on PANC, suggesting that miR-139-5p can be used as a biomarker for PANC patients.

F- Nucleophilic-Addition-Induced [3 + 2] Annulation: Direct Access to CF3-Substituted Indenes.

An efficient [3 + 2] annulation of (2,2-difluorovinyl)-2-iodoarenes and internal alkynes was developed for the synthesis of 1-(trifluoromethyl)-1 H-indenes. The success of this strategy hinges upon a well-balanced process for the generation of two transient reactive species, specifically trifluoroethylsilver and alkenylpalladium intermediates, in the same molecule, as well as a smooth transmetalation step, which delicately joins together these two different metallic intermediates.

Catheterization of the gallbladder: A novel mouse model of severe acute cholangitis.

AIM: To establish a severe acute cholangitis (SAC) model in mice. METHODS: Cholecystic catheterization was performed under the condition of bile duct ligation (BDL). Trans-cholecystic injection of lipopolysaccharide (LPS) was defined as the SAC animal model. Sham operation group, intraperitoneal injection of LPS without BDL group, intraperitoneal injection of LPS with BDL group and trans-cholecystic injection of normal saline with BDL group were defined as control groups. The survival rates and tissue injuries in liver, lungs and kidney were evaluated. RESULTS: Mice in the SAC group showed a time-dependent mortality and much more severe tissue injuries in liver, lungs and kidney, compared with other groups. However, relieving biliary obstruction could effectively reduce mortality and attenuate liver injury in the SAC mouse model. CONCLUSION: Trans-cholecystic injection of LPS under the condition of biliary obstruction could establish a repeatable and reversible mouse model of SAC.

Structure-based bioisosterism design, synthesis, insecticidal activity and structure-activity relationship (SAR) of anthranilic diamide analogues containing 1,2,4-oxadiazole rings.

BACKGROUND: Anthranilic diamide derivatives are among the most important classes of synthetic insecticides. Moreover, the 1,2,4-oxadiazole heterocycle, a bioisostere of amide, has been extensively used in pesticides. In order to discover novel molecules with high insecticidal activities, a series of anthranilic diamide analogues containing 1,2,4-oxadiazole rings were designed and synthesised. RESULTS: A series of novel anthranilic diamide derivatives containing 1,2,4-oxadiazole were obtained, and confirmed by 1 H and 13 C nuclear magnetic resonance and high-resolution mass spectrometry. The structure of 3-bromo-N-(4-chloro-2-methyl-6-{3-[(methylsulphonyl)methyl]-1,2,4-oxadiazol-5-yl}phenyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide was further characterised by X-ray diffraction analysis. In addition, bioassays showed that most of the newly synthesised compounds displayed 100% mortality against Plutella xylostella at 100 mg L-1 , and compound 3IIl showed 90% larvicidal activities at a concentration of 0.5 mg L-1 . The LC50 value of 3IIl was 0.20 mg L-1 , which indicated that it may be used as a potential leading compound for further structural optimisation. Furthermore, brief comparative molecular field analysis (CoMFA) models were established to study the structure-activity relationships (SARs) of the title compounds. CONCLUSION: Compound 3IIl may be used as a potential leading compound for further structural optimisation, and SARs and CoMFA models could provide reliable clues for further structural optimisation. © 2016 Society of Chemical Industry.

Detection of Trypanosoma lewisi from wild rats in Southern China and its genetic diversity based on the ITS1 and ITS2 sequences.

Trypanosoma lewisi has widely been considered as a non-pathogenic rat trypanosome. However, more and more cases of humans infected with T. lewisi have been reported around the world, indicating that it can infect humans in some undetermined circumstances. Quick and sensitive diagnosis of infection by T. lewisi is important for both treatment of patients and epidemiological studies of this parasite. In this paper, three methods i.e. wet blood smear (diagnosis by microscopy), PCR and LAMP were used to detect T. lewisi from 238 wild rats (Rattus norvegicus) collected from the field in Huadu, Guangdong province, China. Infection rates of these samples detected by the 3 methods was 6.7% (16/238), 12.6% (30/238), and 18.9% (45/238), respectively. LAMP could detect all samples shown positive by microscopical observation of wet smear and by single PCR indicating good potential for application in the detection of T. lewisi. So far as we know, this is the first report of the LAMP method being used to detect T. lewisi in wild rats. The specific T. lewisi LAMP primers were able to amplify the target fragment from the genomic DNA of 19 T. lewisi strains isolated from Huadu, Guangdong province (n=16), Changchun, Jilin province of China (n=1) and from Thailand (n=2). Based on the analyses of ITS1 (internal transcribed spacer 1) and ITS2 sequences, these 19 strains show a very close genetic relationship with over 96-97% similarity to the other corresponding sequences of T. lewisi published in Genbank. Phylogenetic trees of the species in the subgenus Herpetosoma were constructed, based on the ITS1 and ITS2 sequences, and these results also indicate that they are closely related and in the same clade.