(NH4)2S2O8 promoted tandem radical cyclization of quinazolin-4(3H)-ones with oxamic acids for the construction of fused quinazolinones under metal-free conditions.

A novel cascade radical addition/cyclization reaction of non-activated olefins and oxamic acids has been proposed. Under transition metal-free conditions, 36 quinazolinone derivatives containing an amide moiety were successfully synthesized, with the highest yield being 81%. This method involves the preparation of aminoacyl fused quinazolinone derivatives under mild conditions, offering advantages such as a high yield, a broad substrate compatibility, and a high atom economy.

Copper-catalyzed C-N Bond Cleavage: Synthesis of N-sulfonylformamidines from N-(2-pyridinylmethyl)benzenesulfonamides.

A broad range of N-sulfonyformamidines, widely used intermediates for drugs, were synthesized in moderate to excellent yields from 2-Pyridinemethanamine as N-source via Coppercatalyzed C-N cleavage. Firstly, N-(2-pyridinylmethyl)benzenesulfonamides were smoothly synthesized via 2-pyridinemethanamine and sulfonyl chlorides, then reacted with N,Ndimethylformamide dimethyl acetal to obtain the corresponding N-Sulfonylformamidines analogs, during which pyridin-2-ylmethyl and sulfonyl groups were essential for the C-N bond cleavage. The current work presents a valuable complementarity to the synthesis of N-sulfonyformamidines as 2- pyridinemethanamine can provide the N source and sulfonyl chloride,s which could be original materials. BACKGROUND: N-sulfonylamidines have gained considerable attention from schools and industries because of their unique bioactivity. Since Pinner's strategy, expanding the synthesis methods of Nsulfonylamidines has been the goal of many organic chemists over the past decades. Besides the crash reaction conditions and the participation of undesirable reagents, the production of Nsulfonylamidines commonly required unstable ammonia and azides as the source of nitrogen that hindered the further development and application of N-sulfonylamidine derivatives. OBJECTIVE: The study aims to find a stable N source to replace NaN3 or NH3 to synthesize N-sulfonylamidines from sulfonyl chlorides. METHODS: Firstly, N-(2-pyridinylmethyl)benzenesulfonamides were smoothly synthesized via 2- pyridinemethanamine and sulfonyl chlorides. Then the reaction conditions of N-(2-pyridinylmethyl) benzenesulfonamides and N,N-dimethylformamide dimethyl acetal (DMF-DMA) were screened and optimized. The reaction was processed in glycol at 80 degree centigrade for 8 hours with the addition of 5 mol% Cu(OAc)2·H2O as a catalyst. RESULTS: Taking advantage of pyridin-2-ylmethyl, a scope of N-Sulfonylformamidines were synthesized from those N-(2-pyridinylmethyl)benzenesulfonamides under copper-catalyzed C-N bond cleavage. CONCLUSION: This ready synthetic method will be more of a promising inspiration for bioactive compound synthesis and drug development than for an innovative approach to synthesizing N-sulfonylformamidines.

Robust Mg(Ca)Zr-Doped Acid-Base Bifunctional Mesoporous Silica and Their Applications in the Deacetalization-Knoevenagel Reaction.

A series of Mg(Ca)Zr-doped acid-base bifunctional mesoporous silica were synthesized to study the impact of the one-step or two-step impregnation method on material structure. The two-step method seems to be a better way to synthesize metal-based functionalized catalyst and their catalytic performance is investigated using deacetalization-Knoevenagel reaction as the probe reaction. The coexisting dual active sites and suitable designing routes endowed highly efficient (Conv. >99.6%, Sel. >99.8%) and robust stability (10 consecutive cycles) of these materials. The present process succeeded in preparing catalysts decorated with acid-base sites by doping acidic and alkali metal species rather than grafting organic groups.

Mechanism of blood-brain barrier disruption by an Escherichia coli from lambs with severe diarrhea and meningoencephalitis.

Escherichia coli (E. coli) is a common conditional pathogen that is associated with a variety of infections in humans and animals. Although there are increasing reports regarding the infection of E. coli to domestic animals and poultry, the infection of E. coli in lambs is relatively less reported, especially on meningoencephalitis. Here, we reported the isolation of an E. coli strain designated as NMGCF-19 from lambs characterized with severe diarrhea and neurological disorder, and demonstrated that NMGCF-19 as the causative agent has the ability to disrupt the blood-brain barrier (BBB) to cause the meningoencephalitis using a mouse model. Investigation on the mechanism regarding the NMGCF-19-related meningoencephalitis revealed a significant decreased expression of ZO-1 and occludin in mouse brain tissue in comparison with the control mice. Moreover, infection of NMGCF-19 increased the expression of proinflammatory cytokines TNF-α, IL-6, IL-1ß and IL-18, up-regulated HMGB1 level, and activated TLR2/TLR4/MyD88 and NLRP3 inflammasome pathways. These findings indicated that NMGCF-19 likely invades the brain tissue by disrupting the tight junction (TJ) architecture and causes the meningoencephalitis via increasing inflammatory response and activating TLR2/TLR4/MyD88 and NLRP3 inflammasome pathways.

Discovery of a virus of the species Enterovirus F in goats.

Here, we report two novel enteroviruses, designated as SD-S67 and SD-S68, isolated from a goat farm. Their complete genome sequences were determined and found to be 7455 and 7465 nucleotides in length, respectively. Molecular characterization revealed that SD-S67 is closely related to bovine enterovirus strain 261 and that SD-S68 to caprine enterovirus strain CEV-JL14. Phylogenetic analysis showed that SD-S67 clustered with members of the species Enterovirus F, and that SD-S68 clustered with enteroviruses of goats and sheep. Recombination analysis showed that SD-S67 is likely to have undergone several recombination events in the process of its evolution. To the best of our knowledge, this is the first report of an enterovirus F isolate from a goat and of a coinfection with enteroviruses of different species in the same goat herd.

Baicalin protects mice against Salmonella typhimurium infection via the modulation of both bacterial virulence and host response.

BACKGROUND: The worsening problems of antibiotic resistance prompt the need for alternative strategies. Baicalin, which is isolated from Scutellaria baicalensisi, has been demonstrated to exhibit anti-inflammatory, anti-virulence and antimicrobial effects. Salmonella typhimurium is an important foodborne pathogenic bacteriaum that causes gastrointestinal disease in humans and many animals. PURPOSE: The aim of this study was to investigate the effects of baicalin on S. typhimurium infection in mice and its possible mechanism in vitro. STUDY DESIGN: To evaluate the effect of baicalin in vivo, mice were orally administered of baicalin, and then were infected by an intragastric administration of S. typhimurium. The minimal inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of baicalin, baicalein, and oroxylin A against S. typhimurium were detected under the guides of the Clinical and Laboratory Standards Institute. In vitro, Caco-2 cells were infected with S. typhimurium in the presence or absence of baicalin, baicalein, and oroxylin A at sub-MICs. METHODS: In the in vivo experiment, the body weight loss, the serum levels of TNFα,  IL-6, and lactic dehydrogenase (LDH), the pathological changes of the caecum and the caecum bacterial burdens were examined. The MICs and MBCs of baicalin, baicalein, and oroxylin A against S. typhimurium were detected by two-fold serial dilutions. In vitro, Caco-2 cells were infected with S. typhimurium, and the invasion capacity, TNFα, nitrate, and LDH were analysed. The transcription levels of Salmonella pathogenicity island 1 virulence associated genes (sopB, sopE, sopE2) of S. typhimurium in the presence of baicalin, baicalein, and oroxylin A were detected by qRT-PCR. RESULTS: Our results showed that baicalin significantly decreased the body weight loss, the serum levels of TNFα,  IL-6, and LDH, and the caecum bacterial burdens of mice challenged with S. typhimurium. Histological examination showed that baicalin decreased the lesion in the caecum of S. typhimurium-infected mice. MICs and MBCs of baicalin, and oroxylin A. against S. typhimurium were > 128 µg/ml. MICs and MBCs of baicalein against S. typhimurium were 64 µg/ml, and > 128 µg/ml, respectively. Pretreatment of Caco-2 cells or S. typhimurium with baicalin, baicalein, and oroxylin A significantly inhibited the invasion of Caco-2 cells by S. typhimurium in a dose-dependent manner. Sub-MICs of baicalin, baicalein, and oroxylin A also significantly decreased the levels of TNFα, nitrate, and LDH from S. typhimurium-infected Caco-2 cells. Moreover, the transcription levels of sopB, sopE, and sopE2 were significantly suppressed by baicalin, baicalein, and oroxylin A. CONCLUSIONS: These results demonstrated that baicalin is a promising agent for the prevention of S. typhimurium infection via the modulation of both bacterial virulence and host response.