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The vapor‐phase nitrilation of dimethyl adipate (DMA) with ammonia (NH3) is an environmentally benign route leading to adiponitrile (ADN) with great application value. In this study, the performance of HZSM‐5 zeolites, widely used in industry as the solid acid catalysts, was investigated. It exhibits a strong correlation between the SiO2/Al2O3 ratio (SAR) in HZSM‐5 zeolites and the reactivity (both activity and selectivity). The influence of Al density closely related to the value of SAR on the reactivity of HZSM‐5 was thus elucidated by mechanistic experiments. As a result, the introduction of Al element to the framework is beneficial to the activation of ester functionality, thus improving the activity, especially at a high liquid hourly space velocity (LHSV). However, a high Al density will lead to poor selectivity and deactivation due to too strong adsorption of esters and intermediates (e. g., amides). Herein, the balanced adsorption/desorption capability was reached on HZSM‐5 with SAR as 631 (i. e., HZSM‐5‐631), which provides the best selectivity to nitriles (SADN+MCP, 92.5 %) at a high single‐pass conversion of DMA (CDMA, 98.0 %). [ABSTRACT FROM AUTHOR]

Aims: Apatinib is widely used in Chinese cancer patients. As the in vivo drug disposition of apatinib has large individual differences, adverse events are prone to occur. Cytochrome P450 (CYP)3A5 and cancer types maybe the main factors affecting this individual differences. The objective of our study was to establish a population pharmacokinetics (PK) model of apatinib in adult cancer patients, and to explore optimal dosage regimens for individualized treatment. Methods: Adult patients with various types of cancer treated with apatinib were enrolled. The concentration of apatinib in plasma was determined by high‐performance liquid chromatography–tandem mass spectrometry. CYP3A5 genotype was determined using TaqMan allelic discrimination technique. The population PK model was developed by NONMEM V7.4. The dosing regimen was optimized based on Monte Carlo simulations. Results: A population PK model of apatinib in adult cancer patient was established. CYP3A5 genotype and systemic cancer type (digestive system cancers, nondigestive system cancers) were the most significant covariates for PK parameters. Patients with CYP3A5*1 expressers (CYP3A5*1/*1 and CYP3A5*1/*3) had lower apparent clearance and apparent volume of distribution than patients who do not express CYP3A5*1 (CYP3A5*3/*3). Patients with nondigestive system cancer had higher apparent volume of distribution and absorption rate constant than digestive system cancer. The results of dose simulation suggest that the apatinib dose in patients who do not express CYP3A5*1 should be 33.33–50.00% higher than that in CYP3A5*1 expressers. Conclusions: A population PK model of apatinib in adult cancer patients was established. CYP3A5 genotype and systemic cancer type had concurrent effects on PK parameters. CYP3A5 patients who do not express CYP3A5*1 required higher doses. [ABSTRACT FROM AUTHOR]

In this study, palladium‐based heterogeneous catalysts were successfully prepared by encapsulating the palladium diphosphine complexes into an imine‐linked 2D‐COF (TPB‐DMTP‐COF) through a one pot self‐assembly approach. It not only prevents the oxidation of phosphine‐based ligand during the stepwise impregnation but also suppresses the coordination of imine linkers at the COF host to the palladium guest, thus enabling highly efficient encapsulation of the active bidentate phosphine chelated palladium complex by the widely explored imine‐linked COF. Besides, the dosage of diphosphine ligand (Xantphos‐SO3H, L) and the ratio of palladium to L in the preparation of [Pd]@COF hybrids can be readily adjusted under such one pot procedure to satisfy the requirement of crystallinity, porosity, active sites, and CO adsorption capacity for the catalytic performance in the methoxycarbonylation of olefins. The resultant [Pd]@COF‐A‐0.25‐0.5 provides satisfied catalytic performance for both aliphatic and aromatic olefins with total esters up to 92.1 % under optimized conditions. These findings provide the basis for a novel design concept to design heterogeneous catalysts with high efficiency for reaction processes comprising the alkoxycarbonylation of olefins. [ABSTRACT FROM AUTHOR]

The laboratory trophic transfer of hexabromocyclododecanes (HBCDs) was studied using predatory (oscar) fish and a prey species (tiger barb) exposed to a technical HBCD. Gut absorption, dynamic changes of diastereomer pattern and enantiomer fractions, and potential metabolism of HBCDs were examined. Compared with β- or γ-HBCD, α-HBCD showed lower absorption efficiency in the gut of oscar fish. A predominance of γ-HBCD was observed in the tiger barb after 5 d HBCD-exposed and oscar feeding on the tiger barb for 16 d. After 20 d of depuration, 41.1% γ-HBCD and 42.7% β-HBCD disappeared, and α-HBCD exceeded the initial amount. The transformation from γ-HBCD predominance in the food to α-HBCD predominance in the oscar was attributed mainly to the isomerization of γ-HBCD (at least 3% and up to 22.7%) to α-HBCD. Selective enrichment of the (+) α- and (−) β-enantiomers and no enantioselective enrichment of γ-HBCD were observed in the tiger barbs. No enantioselective uptake of the 3 diasteromers was found in the oscar gut. The enantiomer fractions of α- and γ-diastereomers were significantly higher, but that of β-diastereomer were significantly lower in the oscars than in the tiger barbs, indicating enantioselective metabolism of the 3 diastereomers. Two HBCD monohydroxylated metabolites were detected in the 2 fish species, but their composition patterns differed, indicating a species-specific metabolism of HBCD in the studied fish species. Environ Toxicol Chem 2013;32:2565-2570. © 2013 SETAC [ABSTRACT FROM AUTHOR]

The article describes the first total synthesis of prionoid E, a secoabietane diterpene quinone isolated from Salvia prionitis, through Wacker oxidation and aldol condensation, the primary steps in the synthetic sequence. Prionoid E was prepared in 15 steps in 3.7% yield beginning from anisole and methylsuccinic anhydride on one hand, and from 2-hydroxy-2-methylpropanoic acid on the other hand. The application of this method to synthesis prionoid E and its analogs for evaluation of their biological activity is reportedly ongoing.

Background and Purpose: Peroxisome proliferator-activated receptors (PPARs) are attractive targets for the treatment of type 2 diabetes and the metabolic syndrome. P633H (2-[4-(2-Fluoro-benzenesulphonyl)-piperazin-1-yl]-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-phenyl}-propionic acid), a novel PPARalpha/gamma dual agonist, was investigated for its very different effects on insulin resistance and dyslipidemia in db/db and KK-A(y) mice.Experimental Approach: The action of P633H at PPARalpha/gamma was characterized by using transactivation assays. Functional activation of PPARalpha/gammain vitro was confirmed by pre-adipocyte differentiation and regulation of target gene expression. Anti-diabetic studies were performed in two different diabetic mice models in vivo.Key Results: P633H activated both PPARalpha and PPAR gamma, (with EC(50) values of 0.012 micromol and 0.032 micromol respectively). Additionally, P633H promoted pre-adipocyte differentiation, up-regulated expression of adipose specific transport protein (aP2) mRNA (3T3-Ll cells) and acyl-CoA oxidase mRNA (LO2 cells). In db/db mice, P633H reduced serum glucose, insulin, triglycerides, non-esterified fatty acids and liver triglycerides. It also improved glucose intolerance without affecting food intake and body weight after 15 days of treatment. However in KK-A(y) mice, hyperglycaemia, dyslipidemia and impaired glucose tolerance were not relieved even after a 25 day treatment with P633H. Further studies with real-time PCR and electron microscopy revealed that P633H promoted progression of diabetes in KK-A(y) mice by increasing hepatic gluconeogenesis and exacerbating pancreatic pathology.Conclusion and Implications: Although P633H was a high-potency PPARalpha/gamma dual agonist, with good functional activity in vitro, it produced opposing anti-diabetic effects in db/db and KK-A(y) mice. [ABSTRACT FROM AUTHOR]

The PSAP organocatalyst is prepared from Boc-protected L-proline in 2 steps. [ABSTRACT FROM AUTHOR]