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A practical and scalable protocol for electrochemical arylation of quinoxalin(on)es with arylhydrazine hydrochlorides under mild conditions has been developed. This method exhibits high efficiency, easy scalability, and broad functional group tolerance. Various quinoxalin(on)es and arylhydrazines underwent this transformation smoothly in an undivided cell, providing the corresponding aryl-substituted quinoxalin(on)es in moderate to good yields. A radical mechanism is involved in this arylation reaction.

Visible light-driven self-catalyzed regulable alkylation of 2H-benzothiazoles with diverse aliphatic C–H donors via the combination of HAT and self-photoredox catalysis.

In this work, the method of combining the various ligands with Raney Ni in continuous flow is proposed, in which triphenylphosphine (TPP) can effectively improve the chemical selectivity of anilines prepared by nitroarenes hydrogenation and maintain high activity. Meanwhile, through the analysis of ICP, FT-IR, XRD, and EDS, we have concluded that the low degree of complexation and the uniform distribution of TPP are presumed be the keys to high selectivity and activity. TPP/Raney Ni exhibits excellent tolerance to halogens and unsaturated functional groups in the continuous flow system of nitroarenes hydrogenation. Furthermore, the practicability of the continuous flow system was tested.

A K2S2O8-catalyzed versatile C(sp2)–C(sp3) bond formation with N-heteroaromatics and γ-lactams/amides was developed. Quinoxalin-2(1H)-one, quinoline, isoquinoline, phthalazine, and benzothiazole reacted with γ-lactams/amides to give the corresponding C(sp2)–H amidoalkylation products in moderate to good yields with high regioselectivity. This visible-light-induced photocatalyst-free reaction was conducted in H2O at ambient temperature, which comply with the principles of “green chemistry”. The new K2S2O8 catalytic mechanism was investigated with control experiments.

An efficient silver-catalyzed δ-regioselective C(sp3)–H heteroarylation of free alcohols has been developed. Various alcohols reacted with quinolines, isoquinoline, pyridines, pyrimidine, phthalazine, 4-hydroxyquinazoline, acridine, quinoxaline and pyrazine to give the corresponding C(sp2)–H alkylation products in 31–89% yields. Notably, all types (1°, 2°, and 3°) of δ-C(sp3)–H bonds in the alcohols could be regioselectively activated. This protocol provides a platform to access divergent functionalizations of alcohols and heteroaryls by forming the challenging δ-selective C(sp3)–C(sp2) bond.

A continuous-flow process for the bromination of conjugated allylic compounds with N-bromosuccinimide (NBS) is developed. The reaction was optimized in a self-made continuous-flow photoreactor based on a commercially available household lamp. The productivity of this continuous step attains 70.5 g/h under the optimal conditions. Compared to batch-mode synthesis, the conversion rate and selectivity of this flow-mode was significantly improved. In addition, the reaction time could be significantly reduced from a few hours to a few minutes.

m-Difluorobenzene is an important structural in many pharmaceutical agents and nature products. However, the conventional method of preparing m-difluorobenzene, which was adopts double diazotization from m-phenylenediamine, is very tricky with potential hazards associated with the strongly exothermic and thermal instability of the diazonium intermediate, and has severe coupled side reactions. Here, we report the continuous-flow methodology, which effectively addresses this series of process challenges by an extra inert solvent flow. The protocol rapidly synthesize m-Difluorobenzene with 85% total yield (the traditional method has 65% total yield). The molar ratio of hydrochloric acid used in the process deduce to 3.6 equivalent (traditional method requires 12 equivalent). Furthermore, the reaction time can be decreased from hours to within 40 s. Above all, the method has potential industrial application value. Graphical abstract

An electrochemical method for the C(sp2)–H thioetherification of quinoxalin-2(1H)-ones with primary, secondary, and tertiary thiols has been reported. Various quinoxalin-2(1H)-ones underwent this t...

An efficient visible-light-induced para-selective C(sp2)-H difluoroalkylation of diverse electron-deficient (hetero)aromatic carbonyls (aldehydes and ketones) at ambient temperature has been developed by employing Ir(ppy)3 as the catalyst and 1,10-phenanthroline as the additive. This protocol was highlighted by its wide substrate scope, high regioselectivity, low catalyst usage, and operational simplicity.

Directed by the strategy of C–H activation, an efficient construction of the isatin skeleton was developed through aerobic oxidation of glycine esters. The reactions were performed under CF3COOH/O2 conditions in the absence of metal catalysts. The reaction mechanisms were investigated with control experiments.

The catalyst-free direct regioselective α-fluoro-β-hydroxylation and α-fluoro-β-amidation of α,β-unsaturated ketones has been developed. Various α,β-unsaturated ketones react with Selectfluor in water and acetonitrile to give α-fluorohydrins and α-fluoroamides respectively with moderate to good yields. The mechanistic studies revealed the possibility of a radical based pathway.

A one-pot, two-step L-proline-mediated stereoselective α-C(sp2)−H fluorination of α,β-unsaturated aldehydes to their corresponding (Z)-α-fluoro-α,β-unsaturated aldehydes has been developed. The first step utilises Selectfluor as a fluorinating agent in CH3NO2/MeOH forming (Z)-α-fluoro-α,β-unsaturated aldehydes and their corresponding dimethyl acetals via methoxyfluorination-elimination. In the second step, water is added to promote the hydrolytic cleavage of the dimethyl acetals. The obtained (Z)-α-fluoro-α,β-unsaturated aldehydes were smoothly reduced to the corresponding alcohols by NaBH4.

A copper-catalyzed cross-dehydrogenative coupling reaction between N-hydroxyphthalimide and aldehydes using PhI(OAc)2 as an oxidant is described. It is reported for the first time to synthesize NHPI esters in water, providing the corresponding NHPI esters in moderate to good yields. This facile and efficient method is eco-friendly and possesses the advantages of mild conditions, short reaction time, and broad substrate scope.

An efficient visible-light-induced

A copper(II)-catalyzed cross dehydrogenative coupling reaction between N-hydroxyphthalimide and unactivated C(sp3)–H bonds of alkanes and ethers using Selectfluor as an oxidant is described. This efficient reaction system shows mild conditions and a broad substrate scope for the generation of O-substituted N-hydroxyphthalimide derivatives.

As a kind of commercial thermoplastic elastomers, thermoplastic vulcanizates (TPVs) have been widely used in many fields. In this work, a shape memory polymer (SMP) was fabricated based on co-continuous polylactide (PLA)/natural rubber (NR)/silica (SiO2) TPVs. Selective distribution of SiO2 nanoparticles was achieved with the impact of thermodynamic factor and different processing methods, and the influence on shape memory behavior was investigated as well. The results demonstrated that the co-continuous structure functioned actively in both shape fixity and recovery. The PLA phase played the role of “switch” to control the shape memory behavior, while the deformation of continuous rubber network stored sufficient resilience and successfully drove the shape recovery process. Excellent shape fixing ratio (~100%) and shape recovery ratio (>90%) were obtained when SiO2 nanoparticles were distributed in NR phase. The addition of SiO2 nanoparticles reinforced the rubber phase and the recovery ratio was effectively improved.

Previous studies have shown that leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is expressed on most types of hamatopoietic cells and negatively regulate immune response, but the roles of LAIR-1 in tumor of the non-hematopoietic lineage have not been determined. Despite advances in therapy of epithelial ovarian cancer (EOC), many questions relating to EOC pathogenesis remain unanswered. The aim of this study was to investigate the clinical significance of LAIR-1 expression in EOC and explore the possible association between LAIR-1 and cancer. In this study, a tissue microarray containing 78 ovarian cancer cases was stained following a standard immunohistochemical protocol for LAIR-1 and the correlation of LAIR-1 expression with clinicopathologic features was assessed. LAIR-1 was detected to express in tumor cells of ovarian cancer tissues (73.1%) and EOC cell lines COC1 and HO8910, not in normal ovarian tissues. In addition, LAIR-1 expression correlates significantly with tumor grade (p = 0.004). Furthermore, down-regulation of LAIR-1 in HO8910 cells increased cell proliferation, colony formation and cell invasion. These data suggest that LAIR-1 has a relevant impact on EOC progression and may be helpful for a better understanding of molecular pathogenesis of cancer.

An effective copper-catalyzed esterification of unactivated (non-benzylic and allylic) C(sp3)–H bonds of hydrocarbons with Selectfluor as an oxidant has been developed. This reaction could provide a direct, new and useful strategy for the synthesis of esters and alkyl alcohols by ester hydrolysis.

// Xiaojie Wu 1, * , Haiyong Jin 2, * , Yueling Zhang 3 , Mingyuan Dong 3 , Xiaoting Wu 3 , Jiadi Zhou 1 , Weishan Zhuge 4 , Jianjing Yang 5 , Qichuan Zhuge 5 , Xiying Luan 1 , Dexiang Ban 6 , Wenjie Zhu 3 , Yongjun Jin 7 and Jiangnan Xue 1 1 Department of Immunology, Binzhou Medical University, Yantai, China 2 Department of Otorhinolaryngology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China 3 Department of Operating Theatre, Binzhou People’s Hospital, Binzhou, China 4 Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China 5 Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China 6 Department of Orthopaedics, Tianjin Medical University General Hospital, Tianjin, China 7 Department of Endocrinology, Yantai Affiliate Hospital, Binzhou Medical University, Yantai, China * These authors contributed equally to this work Correspondence to: Jiangnan Xue, email: xuejinagnan@263.net Yongjun Jin, email: endojin@126.com Keywords: nonalcoholic fatty liver disease; mouse trefoil factor 3; peroxisome proliferator-activated receptor-α; fatty acid oxidation; lipogenesis Received: March 03, 2017 Accepted: December 13, 2017 Published: January 02, 2018 ABSTRACT Hepatic trefoil factor 3 (Tff3) was identified as a potential protein for the treatment of diabetes, yet the mechanisms involved in this effect remain unclear. Moreover, the effect of Tff3 on non-alcoholic fatty liver disease (NAFLD) has never been examined. Here, we show that the expression of hepatic Tff3 was significantly decreased in NAFLD mouse models, indicating that Tff3 was a potential marker gene for NAFLD. Restoring the expression of Tff3 in the liver of NAFLD mice including db/db (diabetic), ob/ob (obese) and DIO (diet-induced obese) mice with adenovirus-mediated Tff3 (Ad-Tff3) attenuates the fatty liver phenotype. In contrast, adenovirus-mediated knockdown of Tff3 (Ad-shTff3) in normal C57BL/6J mice results in an obvious fatty liver phenotype. Furthermore, our molecular experiments indicated that hepatic Tff3 could alleviate hepatic steatosis by directly up-regulating the expression of peroxisome proliferator-activated receptor-α (PPARα), thereby enhancing fatty acid oxidation processes in the liver. Notably, we found that Tff3 attenuates the fatty liver phenotype independent of modulation of lipogenesis and enhances anti-inflammatory effects. Overall, our results suggest that hepatic Tff3 could be effectively used as a potential therapy target for the treatment of NAFLD.

Aim Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is an immune inhibitory receptor which is expressed within most types of hematopoietic cells and negatively regulates immune responses. Recently, we found LAIR-1 expression to be present within tumors of nonhematopoietic lineages. However, the roles of LAIR-1 in hepatocellular carcinoma (HCC) have yet to be examined. The purpose of this study was to investigate the expression of LAIR-1 in HCC tissue and assess its clinical significance at this site. Materials and methods Expression levels of LAIR-1 within HCC samples collected from 90 patients and compared with that of slides of normal liver tissue collected from 9 non-HCC patients were measured by immunohistochemistry using tissue microarrays. A semiquantitative score was assigned, as was based on staining intensity and percent of positive cells and a Spearman Rank correlation test was used to assess any potential significant correlations between LAIR-1 expression and clinicopathological factors. Overall survival analysis was performed using the Kaplan-Meier and Log Rank statistical test. Results LAIR-1 expression was detected in cancer tissue and adjacent tumor tissue, but not in normal liver tissue. The percent of LAIR-1-positive expression in cancer tissue of HCC samples was 97.78% (88/90) while that in adjacent tumor tissue was 96.67% (87/90). Significantly greater expression levels of LAIR-1 were obtained from cancer tissue (Mean ± SD = 5.722 ± 2.145) than that in adjacent tumor tissue (4.141 ± 1.486). In addition, LAIR-1 expression was found to be significantly correlated with pathological grade of HCC, T stage, and age. Expression levels of LAIR-1 were related with worse overall survival rates of HCC patients, especially in HCC patients with hepatic cirrhosis. Conclusion Results of this study show that LAIR-1 is expressed in HCC tissues and that high levels of LAIR-1 expression are associated with the poor cancer differentiation. In addition, overexpression of LAIR-1 was significantly associated with worse overall survival in the patients with HCC. These data suggest that LAIR-1 may be an independent predictor for clinical outcomes in patients with HCC.

A novel process for the preparation of fluticasone propionate (1), a corticosteroid, is reported. In this paper, compound 2 was used as starting material to prepare 6 by using NaClO or NaBrO which was much cheaper than H5IO6 as an oxidizing agent. Furthermore, toxic, expensive, and pollutive BrCH2F was replaced by AgNO3 and Selectfluor in decarboxylative fluorination.

A copper(II)-catalyzed cross dehydrogenative coupling reaction between N-hydroxyphthalimide and unactivated C(sp3)–H bonds of alkanes and ethers using Selectfluor as an oxidant is described. This efficient reaction system shows mild conditions and a broad substrate scope for the generation of O-substituted N-hydroxyphthalimide derivatives.

For the first time, the aza-Morita-Baylis-Hillman reaction of N-sulfonated imines with methyl vinyl ketone was catalyzed by 5,11,17,23-tetrabutyl-25-(diphenylphosphinomethoxy)-26,27,28-trihydroxycalix[4]arene (LB1), an air-stable, easily isolated and reusable catalyst. Great acceleration of the reaction was observed and the aza-Morita-Baylis-Hillman adducts were produced in excellent yields within short reaction time.

An effective copper-catalyzed esterification of unactivated (non-benzylic and allylic) C(sp3)–H bonds of hydrocarbons with Selectfluor as an oxidant has been developed. This reaction could provide a direct, new and useful strategy for the synthesis of esters and alkyl alcohols by ester hydrolysis.

The phosphine substituent acts as Lewis base to initiate the title process and the hydroxy substituents act as Broensted acid to accelerate the reaction and to stabilize the transition state.