Vicinal C-functionalization of alkenes. Pd/light-induced multicomponent coupling reactions leading to functionalized esters and lactones

Under photoirradiation conditions using a xenon light, and in the presence of PdCl(2)(PPh(3))(2) as a catalyst, four-component coupling reactions comprising of α-substituted iodoalkanes, alkenes, carbon monoxide, and alcohols proceeded smoothly to give functionalized esters in good yields. When alkenyl alcohols were used as acceptor alkenes, three-component coupling reactions accompanied by intramolecular esterification proceeded to give lactones in good yields. The present reaction system represents the vicinal C-functionalization of alkenes.     

Catalyzing methanolysis of alkyl halides in the interior of an amphiphilic molecular basket

A molecular basket with four cholate units assembled on a cone-shaped calix[4]arene assumed reversed micelle-like conformation in 5% methanol/carbon tetrachloride. The inwardly facing hydroxyl groups on the cholates concentrated the polar solvent from the mostly nonpolar mixture. Methanolysis of alkyl halides benefited from the concentrated pocket of methanol if the substrate was capable of entering the basket. Substrates that were too large or too hydrophobic to fit within the basket showed no rate acceleration.     

Gold-catalyzed intramolecular hydroalkoxylation/cyclization of conjugated dienyl alcohols

Catalytic intramolecular additions of hydroxyl groups to tethered conjugated dienes are described. The reactions proceed smoothly at 60 °C in the presence of 5 mol % of (PPh₃)AuCl/AgOTf as a catalyst. A broad range of structurally diverse conjugated dienes produce substituted tetrahydrofurans and tetrahydropyrans in good yields. This reaction represents an atom-economic route to construct five- and six-membered cyclic ethers.     

Conformational analysis of N-aryl-N-(2-azulenyl)acetamides

Aromatic amides bearing 2-azulenyl group on the amide nitrogen were synthesized and their structures were investigated. The π-electron density of the N-aryl group was found to influence the cis-trans conformational preferences of these compounds in solution. X-ray crystallography revealed that the plane of the 2-azulenyl ring has a strong tendency to lie coplanar with the amide plane when the azulene group is located on the same side as the amide oxygen atom.     

Dissection of molecular and histological subtypes of papillary thyroid cancer using alternative splicing profiles

Despite growing evidence of the relevance of alternative splicing (AS) to cancer development and progression, the biological implications of AS for tumor behaviors, including papillary thyroid cancer (PTC), remain elusive. With the aim of further understanding the molecular and histological subtypes of PTC, we in this study explored whether AS events might act as new molecular determinants. For this purpose, AS profiles were analyzed in RNA-sequencing data from The Cancer Genome Atlas (TCGA) and from a Korean patient dataset. A total of 23 distinct exon-skipping (ES) events that correlated significantly with PTC oncogenic activity and differentiation scores were identified. The two top-ranked ES events, NUMA1_17515 in exon 18 of NUMA1 and TUBB3_38175 in exon 6 of TUBB3, showed high correlations with oncogenic activities and discriminated histological and molecular subtypes of PTC. Furthermore, two novel intron-retention (IR) events for TUBB3 were uncovered. All ES and IR events for the TUBB3 gene were predicted to induce nonsense-mediated mRNA decay. The relative abundances of intron reads in the PTC dataset from TCGA showed IR levels to differ significantly among PTC subtypes, possibly reflecting their different tumor behaviors. This study provides a landscape of AS changes among PTC subtypes and identified two significant AS events, NUMA1_17515 and TUBB3_38175, as potential AS biomarkers for PTC subclassification and characterization. The AS events identified in this study may be involved in the development of phenotypic differences underlying the functional characteristics and histological differentiation of PTCs.Subject terms: Cancer genomics, RNA splicing     

Isolation of Anti-Diabetic Active Compounds from Benincasae Exocarpium and Development of Simultaneous Analysis by HPLC-PDA

Diabetes is a chronic metabolic disease that is a constant problem. Previous studies have reported that Benincasa cerifera Savi. extracts are effective in treating diabetes and its complications. Benincasae Exocarpium (BE) is a fruit peel of B. cerifera that has been reported to be used for the prevention and treatment of metabolic diseases such as hyperglycemia, obesity, and hyperlipidemia. However, there are not enough studies on the compounds and bioassays to support the efficacy of BE. The inhibitory activity of the BE extracts and fractions against advanced glycation end-products (AGE) formation and α-glucosidase activity was evaluated. These assays are relevant for the treatment of type 2 diabetes and its complications. Based on these results, compounds 1–11 were isolated through bioassay-guided isolation. In addition, we developed a high-performance liquid chromatography (HPLC) method that can simultaneously analyze these 11 compounds. Activity evaluation of the compounds was also conducted, and eight compounds exhibited significant activity. Among these, flavonoid compounds showed strong activity. A quantitative evaluation of eight bioactive compounds (2, 5–11) was conducted. In conclusion, this study demonstrated the potential of BE for prevention and treatment of type 2 diabetes and its complications.     

Promoting grain growth in Ni-rich single-crystal cathodes for high-performance lithium-ion batteries through Ce doping

Journal of Solid State Electrochemistry - Preparing a high-performance Ni-rich single-crystal cathode for Li-ion batteries is challenging. This is because calcination must be performed at a high...     

ESR Study of a Nitroxide Radical in Sol-Gel Glasses

A spin probe TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidinyl-1-oxy) was dissolved in a tetraethyl orthosilicate sol-gel reaction system and measured by electron spin resonance spectroscopy at 295 K. The nitrogen hyperfine coupling constant was from 1.64–1.66 mT in the sol-gel solutions. The values were sensitive to the ethanol-to-water ratio of the solutions. The hyperfine coupling constant in the xerogels was 1.70 mT, which was almost the same as that in water, indicating that the probe molecules were trapped in silica pores with water adsorbed on the silica surfaces. The motion of TEMPOL in the xerogels was considerably slower than in the sol-gel solutions. The local viscosity estimated was from 70–90 cP. The ESR spectra of TEMPOL were altered during the sol-gel process, indicating that adsorbed water on the silicas surfaces has an important role for trapping organic molecules in sol-gel glasses.     

Analysis of transient membrane protein interactions by single-molecule diffusional mobility shift assay

Various repertoires of membrane protein interactions determine cellular responses to diverse environments around cells dynamically in space and time. Current assays, however, have limitations in unraveling these interactions in the physiological states in a living cell due to the lack of capability to probe the transient nature of these interactions on the crowded membrane. Here, we present a simple and robust assay that enables the investigation of transient protein interactions in living cells by using the single-molecule diffusional mobility shift assay (smDIMSA). Utilizing smDIMSA, we uncovered the interaction profile of EGFR with various membrane proteins and demonstrated the promiscuity of these interactions depending on the cancer cell line. The transient interaction profile obtained by smDIMSA will provide critical information to comprehend the crosstalk among various receptors on the plasma membrane.Subject terms: Fluorescence imaging, Super-resolution microscopy, Single-molecule biophysics     

Neuroprotective Effect and Antioxidant Potency of Fermented Cultured Wild Ginseng Root Extracts of Panax ginseng C.A. Meyer in Mice

Wild ginseng has better pharmacological effects than cultivated ginseng. However, its industrialization is limited by the inability to grow wild ginseng on a large scale. Herein, we demonstrate how to optimize ginseng production through cultivation, and how to enhance the concentrations of specific ginsenosides through fermentation. In the study, we also evaluated the ability of fermented cultured wild ginseng root extract (HLJG0701-β) to inhibit acetylcholinesterase (AChE), as well as its neuroprotective effects and antioxidant activity. In in vitro tests, HLJG0701-β inhibited AChE activity and exerted neuroprotective and antioxidant effects (showing increased catalyst activity but decreased reactive oxygen species concentration). In in vivo tests, after HLJG0701-β was orally administered at doses of 0, 125, 250, and 500 mg/kg in an animal model of memory impairment, behavioral evaluation (Morris water maze test and Y-maze task test) was performed. The levels of AChE, acetylcholine (ACh), blood catalase (CAT), and malondialdehyde (MDA) in brain tissues were measured. The results showed that HLJG0701-β produced the best results at a dose of 250 mg/kg or more. The neuroprotective mechanism of HLJG0701-β was determined to involve the inhibition of AChE activity and a decrease in oxidative stress. In summary, both in vitro and in vivo tests confirmed that HJG0701-β administration can lead to memory improvement.