SBA-15 Supported 1-Methyl-2-azaadamanane N-Oxyl (1-Me-AZADO) as Recyclable Catalyst for Oxidation of Alcohol.

Herein, we designed and synthesized an SBA-15 supported 1-methyl-2-azaadamanane N-oxyl (1-Me-AZADO) and investigated its catalytic performance for selective oxidation of alcohols under Anelli's conditions. The first example of immobilization of 1-Me-AZADO was very important to advance the oxgenation effectively because this supported N-oxyl has excellent catalytic activity for oxidation of alcohols to carbonyl compounds, and more importantly, it can be conveniently recovered and reused at least 6 times without significant effect on its catalytic efficiency.

A chromatography-free and aqueous waste-free process for thioamide preparation with Lawesson's reagent.

After completing the thio-substitution with Lawesson's reagent, ethanol was found to be effective in the decomposition of the inherent stoichiometric six-membered-ring byproduct from the Lawesson's reagent to a highly polarized diethyl thiophosphonate. The treatment significantly simplified the following chromatography purification of the desired thioamide in a small scale preparation. As scaling up the preparation of two pincer-type thioamides, we have successfully developed a convenient process with ethylene glycol to replace ethanol during the workup, including a traditional phase separation, extraction, and recrystallization. The newly developed chromatography-free procedure did not generate P-containing aqueous waste, and only organic effluents were discharged. It is believed that the optimized procedure offers the great opportunity of applying the Lawesson's reagent for various thio-substitution reactions on a large scale.

Ni-catalyzed reductive decyanation of nitriles with ethanol as the reductant.

A nickel-catalyzed reductive decyanation of aromatic nitriles has been developed, in which the readily available and abundant ethanol was applied as the hydride donor. Various functional groups on the aromatic rings, such as alkoxyl, amino, imino and amide, were compatible in this catalytic protocol. Heteroaryl, benzylic and alkenyl nitriles were also tolerated. Mechanistic investigation indicated that ethanol provided hydride efficiently via ß-hydride elimination in this reductive decyanation.

Tandem Synthesis of 2-Carboxybenzofurans via Sequential Cu-Catalyzed C-O Coupling and Mo(CO)6-Mediated Carbonylation Reactions.

A modular tandem synthesis of 2-carboxybenzofurans from 2-gem-dibromovinylphenols has been established based on a sequence of Cu-catalyzed intramolecular C-O coupling and Mo(CO)6-mediated intermolecular carbonylation reactions. This protocol allowed one-step access to a broad variety of functionalized benzofuran-2-carboxylic acids, esters, and amides in good to excellent yields under Pd- and CO gas-free conditions.

Quantitative Analysis of the Proteome and the Succinylome in the Thyroid Tissue of High-Fat Diet-Induced Hypothyroxinemia in Rats.

Hypothyroidism is a common disease, and its molecular mechanism still needs further investigation. Lysine succinylation is found to be involved in various metabolic processes associated with hypothyroidism. We performed quantitative analysis on lysine succinylome in thyroids of rats with hypothyroxinemia, which was induced through the administration of a high-fat diet. Overall, 129 differentially expressed proteins were quantified. Downregulated proteins were enriched in the thyroid hormone synthesis and thyroid hormone signaling pathways and were mainly localized in the mitochondria. In addition, 172 lysine succinylation sites on 104 proteins were obviously changed. Decreased succinylated proteins were involved in diverse metabolic pathways and were primarily localized in mitochondria. Finally, the mitochondrial oxygen consumption rates of human normal thyroid epithelial cells were measured to further verify the role of lysine succinylation. The mitochondrial oxygen consumption rates were markedly blunted in the cells treated with palmitic acid (all p < 0.05), and the changes were reversed when the cells were treated with palmitic acid and desuccinylase inhibitor together (all p < 0.05). Thus, we theorize that the thyroid differentially expressed proteins and changed succinylation levels played potential roles in the mitochondria-mediated energy metabolism in the high-fat diet-induced hypothyroxinemia rat model.

Inhibition of miR-383 suppresses oxidative stress and improves endothelial function by increasing sirtuin 1.

Previous research has shown that suppression of miR-383 can prevent inflammation of the endothelium, as well as postpone the development of atherosclerosis. However, the role of miR-383 in endothelial cell apoptosis in diabetes remains unclear. The aim of this study was to investigate the function of miR-383 in high glucose-induced apoptosis and oxidative stress in endothelial cells. A series of experiments involving qualitative polymerase chain reaction, cell transfection, luciferase assay, assessment of cell death, detection of catalase and superoxide dismutase concentrations, detection of intracellular reactive oxygen species (ROS), and western blot analysis were performed in this study. We found that miR-383 expression was promoted, while NAD+-dependent deacetylase and sirtuin 1 (SIRT1) expressions were suppressed in the endothelium of the aorta in db/db mice as well as in human umbilical vein endothelial cells, which were treated with high glucose (HG). Increased expression of miR-383 decreased expression of SIRT1, while suppression of miR-383 promoted expression of SIRT1 in human umbilical vein endothelial cells (HUVECs). Furthermore, suppression of miR-383 following transfection with miR-383 suppressor repressed cell death and generation of ROS in HUVECs. SIRT1 knockdown by siRNA-SIRT1 reversed the suppressive effect of miR-383 inhibition on ROS production and cell apoptosis induced by HG treatment. Overall, the findings of our research suggested that suppression of miR-383 repressed oxidative stress and reinforced the activity of endothelial cells by upregulation of SIRT1 in db/db mice, and targeting miR-383 might be promising for effective treatment of diabetes.

Inhibition of miR-383 suppresses oxidative stress and improves endothelial function by increasing sirtuin 1

Previous research has shown that suppression of miR-383 can prevent inflammation of the endothelium, as well as postpone the development of atherosclerosis. However, the role of miR-383 in endothelial cell apoptosis in diabetes remains unclear. The aim of this study was to investigate the function of miR-383 in high glucose-induced apoptosis and oxidative stress in endothelial cells. A series of experiments involving qualitative polymerase chain reaction, cell transfection, luciferase assay, assessment of cell death, detection of catalase and superoxide dismutase concentrations, detection of intracellular reactive oxygen species (ROS), and western blot analysis were performed in this study. We found that miR-383 expression was promoted, while NAD+-dependent deacetylase and sirtuin 1 (SIRT1) expressions were suppressed in the endothelium of the aorta in db/db mice as well as in human umbilical vein endothelial cells, which were treated with high glucose (HG). Increased expression of miR-383 decreased expression of SIRT1, while suppression of miR-383 promoted expression of SIRT1 in human umbilical vein endothelial cells (HUVECs). Furthermore, suppression of miR-383 following transfection with miR-383 suppressor repressed cell death and generation of ROS in HUVECs. SIRT1 knockdown by siRNA-SIRT1 reversed the suppressive effect of miR-383 inhibition on ROS production and cell apoptosis induced by HG treatment. Overall, the findings of our research suggested that suppression of miR-383 repressed oxidative stress and reinforced the activity of endothelial cells by upregulation of SIRT1 in db/db mice, and targeting miR-383 might be promising for effective treatment of diabetes.

Bidentate Geometry-Constrained Iminopyridyl Ligands in Cobalt Catalysis: Highly Markovnikov-Selective Hydrosilylation of Alkynes.

Reported herein is a well-defined bidentate geometry-constrained iminopyridyl cobalt complex for an efficient and highly Markovnikov-selective hydrosilylation of alkynes, featuring a broad substrate scope including aromatic/heteroaromatic/aliphatic alkynes and primary/secondary silanes. TON is up to 4950. The kinetic study together with structures clearly revealed that the ligand played the key effect on the efficiency.

Pd-Catalyzed reductive heck reaction of olefins with aryl bromides for Csp2-Csp3 bond formation.

We developed a Pd-catalyzed intermolecular reductive Heck reaction to construct Csp2-Csp3 bonds between aryl bromides and olefins. Various styrene derivatives, acyclic and cyclic alkenes, were well tolerated to couple with varied aryl bromides in linear selectivity. Kinetic and deuterium labeling experiments suggested that i-PrOH provides a hydride through ß-H elimination.

An efficient Pd-NHC catalyst system in situ generated from Na2PdCl4 and PEG-functionalized imidazolium salts for Mizoroki-Heck reactions in water.

Three PEG-functionalized imidazolium salts L1-L3 were designed and prepared from commercially available materials via a simple method. Their corresponding water soluble Pd-NHC catalysts, in situ generated from the imidazolium salts L1-L3 and Na2PdCl4 in water, showed impressive catalytic activity for aqueous Mizoroki-Heck reactions. The kinetic study revealed that the Pd catalyst derived from the imidazolium salt L1, bearing a pyridine-2-methyl substituent at the N3 atom of the imidazole ring, showed the best catalytic activity. Under the optimal conditions, a wide range of substituted alkenes were achieved in good to excellent yields from various aryl bromides and alkenes with the catalyst TON of up to 10,000.

N-Heterocyclic carbene copper-catalyzed direct alkylation of terminal alkynes with non-activated alkyl triflates.

(NHC)-Cu-catalyzed C(sp)-C(sp3) bond formation has been successfully achieved under mild conditions. Nonactivated alkyl triflates, which could be easily derived from alcohols, were utilized as C-O electrophiles. Mechanistic studies suggested that copper acetylide was the active species. Scale-up reactions further demonstrated the practicality and efficiency of the developed strategy.

Highly bulky and stable geometry-constrained iminopyridines: Synthesis, structure and application in Pd-catalyzed Suzuki coupling of aryl chlorides.

A series of bulky geometry-constrained iminopyridylpalladium chlorides were developed. The steric environment adjacent to the nitrogen atom in the pyridine rings and diimine parts enhanced the thermal stability of the palladium species. Bulkier groups at the imino group stabilized the palladium species and the corresponding palladium chlorides showed high activities in the coupling reaction of aryl chlorides.

Molecularly imprinted polymers as the extracted sorbents of clenbuterol ahead of liquid chromatographic determination.

A pre-treatment methodology for clenbuterol hydrochloride (CLEN) isolation and enrichment in a complex matrix environment was developed through exploiting molecularly imprinted polymers (MIPs). CLEN-imprinted polymers were synthesized by the combined use of ally-ß-cyclodextrin (ally-ß-CD) and methacrylic acid (MAA), allyl-ß-CD and acrylonitrile (AN), and allyl-ß-CD and methyl methacrylate (MMA) as the binary functional monomers. MAA-linked allyl-ß-CD MIPs (M-MAA) were characterized by Fourier transform-infrared (FT-IR) spectroscopy and a scanning electron microscope (SEM). Based upon the results, M-MAA polymers generally proved to be an excellent selective extraction compared to its references: AN-linked allyl-ß-CD MIPs (M-AN) and MMA-linked allyl-ß-CD MIPs (M-MMA). M-MAA polymers were eventually chosen to run through a molecularly imprinted solid-phase extraction (MISPE) micro-column to enrich CLEN residues spiked in pig livers. A high recovery was achieved, ranging from 91.03% to 96.76% with relative standard deviation (RSD) ≤4.45%.

A mild copper-catalyzed aerobic oxidative thiocyanation of arylboronic acids with TMSNCS.

A facile and efficient transformation of arylboronic acids to their corresponding aryl thiocyanates has been successfully developed. Based on the CuCl-catalyzed oxidative cross-coupling reaction between arylboronic acids and trimethylsilylisothiocyanate (TMSNCS) under oxygen atmosphere, the transformation can be readily conducted at ambient temperature. The newly-developed protocol provided a competitive synthetic approach to aryl thiocyanates that can tolerate a broad range of reactive functional groups and/or strong electron-withdrawing groups.

Thyroid-stimulating hormone regulates hepatic bile acid homeostasis via SREBP-2/HNF-4α/CYP7A1 axis.

BACKGROUND & AIMS: Bile acids (BAs) play a crucial role in dietary fat digestion and in the regulation of lipid, glucose, and energy metabolism. Thyroid-stimulating hormone (TSH) is a hormone produced by the anterior pituitary gland that directly regulates several metabolic pathways. However, the impact of TSH on BA homeostasis remains largely unknown. METHODS: We analyzed serum BA and TSH levels in healthy volunteers under strict control of caloric intake. Thyroidectomized rats were administered thyroxine and injected with different doses of TSH. Tshr(-/-) mice were supplemented with thyroxine, and C57BL/6 mice were injected with Tshr-siRNA via the tail vein. The serum BA levels, BA pool size, and fecal BA excretion rate were measured. The regulation of SREBP-2, HNF-4α, and CYP7A1 by TSH were analyzed using luciferase reporter, RNAi, EMSA, and CHIP assays. RESULTS: A negative correlation was observed between the serum levels of TSH and the serum BA levels in healthy volunteers. TSH administration led to a decrease in BA content and CYP7A1 activity in thyroidectomized rats supplemented with thyroxine. When Tshr was silenced in mice, the BA pool size, fecal BA excretion rate, and serum BA levels all increased. Additionally, we found that HNF-4α acts as a critical molecule through which TSH represses CYP7A1 activity. We further confirmed that the accumulation of mature SREBP-2 protein could impair the capacity of nuclear HNF-4α to bind to the CYP7A1 promoter, a mechanism that appears to mediate the effects of TSH. CONCLUSIONS: TSH represses hepatic BA synthesis via a SREBP-2/HNF-4α/CYP7A1 signaling pathway. This finding strongly supports the notion that TSH is an important pathophysiological regulator of liver BA homeostasis independently of thyroid hormones.

Hexachlorocyclotriphosphazene (HCCP)-mediated direct formation of thioethers and ethers from quinazolin-4(3H)-ones.

A hexachlorocyclotriphosphazene (HCCP)-mediated direct formation of quinazoline (thio)ethers from quinazolin-4(3H)-ones has been developed. Treatment of quinazolin-4(3H)-ones with HCCP, diisopropylethylamine (DIPEA), and thiophenols resulted in formation of the corresponding 4-arylthioquinazoline derivatives in moderate to excellent yields. This method has also been utilized to prepare 4-aryloxyquinazoline and 4-alkoxyquinazoline derivatives using phenols and sodium alkoxides as the nucleophiles.

A general and facile one-pot process of isothiocyanates from amines under aqueous conditions.

A general and facile one-pot protocol for the preparation of a broad range of alkyl and aryl isothiocyanates has been developed from their corresponding primary amines under aqueous conditions. This synthetic process involves an in situ generation of a dithiocarbamate salt from the amine substrate by reacting with CS(2) followed by elimination to form the isothiocyanate product with cyanuric acid as the desulfurylation reagent. The choice of solvent is of decisive importance for the successful formation of the dithiocarbamate salt particularly for highly electron-deficient substrates. This novel and economical method is suitable for scale-up activities.

Switching the chemoselectivity in the amination of 4-chloroquinazolines with aminopyrazoles.

The chemoselectivity in the amination of 4-chloroquinazolines with 3-amino-1H-pyrazoles was studied. Under the conditions of Pd(2)(dba)(3)/Xantphos/Na(2)CO(3), 4-chloroquinazolines underwent selective amination with the cyclic secondary amino group of 3-amino-1H-pyrazoles, whereas 4-chloroquinazolines were exclusively aminated with the primary amino group of 3-amino-1H-pyrazoles via S(N)Ar substitution in the presence of HCl.

Efficient NO equivalent for activation of molecular oxygen and its applications in transition-metal-free catalytic aerobic alcohol oxidation.

tert-Butyl nitrite (TBN) was identified as an efficient NO equivalent for the activation of molecular oxygen. The unique property of TBN enabled TEMPO-catalyzed aerobic alcohol oxidation to be performed in high-volume efficiency. Up to a 16,000 turnover number was achieved in this transition-metal-free aerobic catalytic system. Under the optimal reaction conditions, various alcohols were converted into their corresponding carbonyl compounds with TEMPO/HBr/TBN as catalyst. The newly developed method was suitable for the oxidation of solid substrate alcohols with high melting point and/or low solubility under the help of minimum solvent to form a slurry.

Adsorptive stripping voltammetric determination of netilmicin in the presence of formaldehyde.

A linear sweep adsorptive stripping voltammetric method for the determination of netilmicin in the presence of formaldehyde has been proposed for the first time. In the presence of 3.0 x 10(-3) g ml(-1) formaldehyde, netilmicin exhibits a sensitive cathodic peak at -1.30 V (vs. the saturated calomel electrode, SCE) in a medium of Britton-Robinson buffer (pH 8.7) with a scan rate of 100 mV s(-1) after a preconcentration period of 120 s at -1.10 V (vs. SCE). The peak current showed a linear dependence on the netilmicin concentration over the range 4.2 x 10(-9)-1.0 x 10(-7) g ml(-1). The achieved limits of detection and quantitation were 1.0 x 10(-10) and 3.3 x 10(-10) g ml(-1) netilmicin, respectively. It was deduced from the experiments that the amine-aldehyde condensation product formed between netilmicin and formaldehyde is mainly responsible for the appearance of the peak. The electrochemical behavior of netilmicin in the presence of formaldehyde has been studied. The method was applied to the direct determination of netilmicin in injectable formulations and spiked human urine and serum samples.