Copper-Catalyzed Domino Three-Component Benzannulation: Access to Isoquinolines

We report herein the synthesis of isoquinolines through a copper­(I)-catalyzed domino reaction. During this transformation, three molecules of terminal alkynes, 2-bromoaryl aldehydes (ketones), and acetamide react together, in a sequence including Sonogashira coupling, condensation, 6-endo-dig cyclization, elimination of acetic acid, and hydrolysis. In this reaction, isoquinolines with broad functional group tolerance were successfully obtained by using acetamide as nitrogen source, which provides an alternative to odorous and toxic amines

East China Plains: A “Basin” of Ozone Pollution

Economic growth and associated pollution emissions in China are concentrated over three connected plains to the east. In this work, we analyze an episode of highly elevated ozone over East China on June 9−14, 2004, using a 3-D chemical transport model. During this episode, the East China plains were under a high-pressure system, which suppressed the ventilation of pollutants from the boundary layer. Simulated ozone concentrations over a major fraction of East China reached high levels, all the way down to the Pearl River Delta region in the southern border. The convergence of pollutant emissions and population over the vast stretch of the geographically flat plains of East China makes the region susceptible to high-ozone exposure. During this episode, the high-O3 region extended over an area >1 million km2, which hosts a population of >800 million people. Model results indicate that controlling anthropogenic NOx emissions effectively reduces the area with high-ozone exposure

Ru- and Co-Catalyzed Intermolecular Carbonyl–Alkyne Metathesis Reactions of 1<i>H</i>‑Indene-1,2,3-triones with Internal Alkynes

The catalyst-dependent intermolecular carbonyl–alkyne metathesis (CAM) reaction of 1H-indene-1,2,3-triones with internal alkynes was realized using Ru and Co catalysts. 2-(2-Oxo-1,2-diphenylethylidene)-1H-indene-1,3­(2H)-dione derivatives were obtained using a Ru catalyst, whereas S-alkyl 2-(1,3-dioxo-1,3-dihydro-2H-inden-2-ylidene)-2-phenylethanethioates were prepared using a Co catalyst. These transformations led to the synthesis of α,β-unsaturated carbonyl compounds with a broad substrate scope, excellent regiocontrol, and gram-scale amenability. This catalytic strategy using a Co or Ru catalyst has rarely been described for other established CAM catalysts

Additional file 1 of TGF-β-activated circRYK drives glioblastoma progression by increasing VLDLR mRNA expression and stability in a ceRNA- and RBP-dependent manner

Supplementary Material

Ligand-Controlled Nickel-Catalyzed Reactions of Benzocyclobutenones with Alkynyltrifluoroborates: Diverse Construction of Polysubstituted Naphthols

Ligand-controlled nickel-catalyzed selective cleavage of the C1–C2 or C1–C8 bond of benzocyclobutenones (BCBs) is reported. The delicate selection of dpppe or PMe3 as the ligand led to predictably divergent synthesis of a wide range of 1-naphthols and 2-naphthols without C2 and C3 substituents, respectively, from BCBs and potassium alkynyltrifluoroborate, and the increase in the amount of PMe3 resulted in tandem reaction of 2 equiv of BCB with the borate to afford 3,4,5-trisubstituted 2-naphthols. The fabulous ligand effect resulted in the facile and unique construction of multisubstituted naphthols with well-controlled regioselectivity and a high degree of structural diversity

LiN(SiMe₃)₂/KO^tBu-Promoted Synthesis of Isoquinolone Derivatives from 2‑Methylaryl Aldehydes and Nitriles

A convenient method is proposed for the synthesis of isoquinolone derivatives from 2-methylaryl aldehydes and nitriles through LiN­(SiMe3)2/KOtBu-promoted formal [4 + 2] cycloaddition reaction, featuring high atomic economy, good functional group tolerance, and easy operation. It enables the efficient formation of new C–C and C–N bonds toward isoquinolones without using preactivated amides

Alkaline-Metal-Promoted Divergent Synthesis of 1‑Aminoisoquinolines and Isoquinolines

Alkaline-metal-promoted divergent syntheses of 1-aminoisoquinolines and isoquinolines have been reported involving 2-methylaryl aldehydes, nitriles, and LiN(SiMe3)2 as reactants. In addition, the three-component reaction of 2-methylaryl nitriles, aldehydes, and LiN(SiMe3)2 has been developed to furnish 1-aminoisoquinolines. This protocol features readily available starting materials, excellent chemoselectivity, broad substrate scope, and satisfactory yields

Additional file 1 of Lack of relationship between PROX1 expression and clinicopathological parameters and prognosis in gastric cancer patients: a meta-analysis and TCGA analysis

Additional file 1: Supplementary Table 1. Results for the meta-analysis between PROX1 expression and clinicopathological parameters of GC

Nucleotide Dynamics at the A-Site Cleft in the Peptidyltransferase Center of <i>H. marismortui</i> 50S Ribosomal Subunits

Resistance mutations to antibiotics targeting rRNA can be far from the drug-binding site. Crystallography studies revealed that the antibiotic resistance mutation G2482A (G2447A in E. coli) in Haloarcula marismortui 50S ribosomes does not directly contact the drug or introduce changes to the ribosomal structure except for losing a potassium ion coordinated to a base triple at the drug-binding site. Using molecular dynamics simulations, we tested hypotheses regarding the effects of the G2482A mutation and ion coordination on the conformational dynamics of the 50S ribosome. Simulations show that the mutation enhances conformational fluctuation at the antibiotic binding site, weakens the hydrogen-bonding network, and increases flexibility at the 50S peptidyl transferase center (PTC). Our data supports the view that distant mutations can perturb the dynamic network in the ribosomal PTC, thereby raising the entropic cost of antibiotic binding. These results underscore the importance of considering conformational dynamics in rational drug design

Summertime Clean-Background Ozone Concentrations Derived from Ozone Precursor Relationships are Lower than Previous Estimates in the Southeast United States

Background ozone in this study is defined as the amount of ozone that is not affected by the emissions of ozone precursors in the region of study and is transported from the distant troposphere or the stratosphere. It is one of the factors that must be considered in regional ozone control strategies. Different methods have been applied to define the background ozone level. We develop a new method based on the O3–CO–HCHO relationships, which can be applied to both observation and modeling data for regions with high isoprene emission ozone, such as the Southeast United States. We make use of the extensive aircraft and surface observations in the Southeast in the summer of 2013. Compared to the diagnostic results using the relationship of O3–NOz (total reactive nitrogen excluding nitrogen oxides), zero-emission (model-only), and 5th percentile methods, the new method is most consistent using observation or model data and the resulting background ozone concentrations are 4–50% lower than the other methods for field campaigns. Using this method, we find that the summertime background ozone at the surface is in the range of 10–15 ppbv in the inland areas of the Southeast, which is lower than that reported in previous studies. This background ozone tends to increase from urban centers to rural regions and from the surface to higher altitude due to changing ozone lifetime driven by anthropogenic emissions and dry deposition to the surface. The better quantification of background ozone using the new method highlights the importance of the contributions by natural emissions to ozone and the necessity to control anthropogenic emissions in ozone nonattainment areas of the Southeast