Electrochemical Tri- and Difluoromethylation-Triggered Cyclization Accompanied by the Oxidative Cleavage of Indole Derivatives

Considering their unique roles in organic synthesis, and pharmaceutical and agrochemical applications, the development of fluoroalkylation, cyclization, and indole oxidative cleavage are important topics. Herein, an unprecedented electrochemical tri- and difluoromethylation/cyclization/indole oxidative cleavage process occurring in an undivided cell is presented. The protocol employs a readily prepared Langlois reagent as the fluoroalkyl source, affording a series of tri- or difluoromethylated 2-(2-acetylphenyl)isoquinoline-1,3-diones in good yields with excellent stereoselectivity. It is worth noting that this new methodology merges the fluoroalkylation/cyclization of N-substituted acrylamide alkenes with the oxidative cleavage of an indole C(2)=C(3) bond under external oxidant-free conditions.     

Quantitative study of cellular heterogeneity in doxorubicin uptake and its pharmacological effect on cancer cells

Cellular heterogeneity in doxorubicin (DOX) uptake and its relationship with pharmacological effect on cancer cells were quantitatively investigated for the first time. An in vitro experimental model was established by treating human leukemia K562 and breast cancer MCF‐7 cells with different schedules of DOX with or without surface P‐glycoprotein (P‐gp) inhibitor verapamil (VER). The cellular heterogeneity in DOX uptake was quantitatively examined by single‐cell analysis using capillary electrophoresis coupled with laser‐induced fluorescence detection. The corresponding cytotoxic effect was tested by cellular morphology, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐tetrazolium and flow cytometry assays. The expression of cellular membrane surface P‐gp was determined by flow cytometry. Results showed that the cellular heterogeneity exists in DOX uptake. The single‐high DOX schedule leads to lower uptake heterogeneity and higher mean drug uptake. The cellular heterogeneity in DOX uptake was found to be negatively correlated with drug cytotoxicity and surface P‐gp expression, with r = ?0.7680 to ~ ?0.9587. VER reduces the cellular variation in DOX uptake, suggesting that surface P‐gp may be one of the causes of the cellular heterogeneity in DOX uptake. This research demonstrates the importance of quantitative study of cellular heterogeneity in drug uptake and its potential application in drug schedule design, response prediction and therapy modulation. Copyright © 2014 John Wiley & Sons, Ltd.     

Telaprevir fragments as organocatalysts in asymmetric direct aldol reactions of aldehydes

We have demonstrated that the fragments of Telaprevir can act as organocatalysts for asymmetric aldol reactions between aromatic aldehydes and acetone under mild conditions. The reaction conditions have been optimized in terms of the catalyst nature, choice of temperature, solvent, additive, and the catalyst loading. Under proper conditions, fairly good yield and enantioselectivity have been achieved.     

Synthesis of Diverse Functionalized Quinoxalines by Oxidative Tandem Dual C−H Amination of Tetrahydroquinoxalines with Amines

The tandem dual C−H amination of tetrahydroquinoxalines with free amines under aerobic copper catalysis conditions has been demonstrated. The synthetic protocol proceeds with good substrate and functional group compatibility, mild reaction conditions, short reaction time, the use of the naturally abundant [Cu]/O₂ catalyst system, excellent chemoselectivity and synthetic efficiency, and with no need for the pre-installation of specific aminating agents, which offers a practical platform for the rapid and diverse synthesis of diaminoquinoxalines. Moreover, this work has shown the potential of single-electron-oxidation-induced C−H functionalization of N-heterocycles, and its application in the development of optoelectronic materials.     

Tissue distribution and excretion study of neopanaxadiol in rats by ultra‐performance liquid chromatography quadrupole time‐of‐flight mass spectrometry

Neopanaxadiol (NPD), a major ginsenoside in Panax ginseng C. A. Meyer (Araliaceae), was reported to have neuroprotective effect. In this study, a method of ultra‐performance liquid chromatography quadrupole time‐of‐flight mass spectrometry (UPLC/QTOF‐MS) was developed and validated for quantitative analysis of NPD in tissues, urine and feces, using liquid–liquid extraction (LLE) to isolate NPD from different biological samples, and chromatographic separation was performed on an Agilent Zorbax Stable Bond C₁₈ (2.1 × 50 mm, 1.8 µm) column with 0.1% formic acid in water and acetonitrile. All standard calibration curves were linear (all r² > 0.995) within the test range. After oral administration, NPD was extensively distributed to most of the tissues without long‐term accumulation. The higher levels were observed in stomach and intestine, followed by kidney and liver. Approximately 64.56 ± 20.32% of administered dose in feces and 0.0233 ± 0.0356% in urine were found within 96 h, which indicated that the major elimination route was fecal excretion. This analytical method was applied to the study of NPD distribution and excretion in rats after oral intake for the first time. The results we found here are helpful for us to understand the pharmacological effects of NPD, as well as its toxicity. Copyright © 2014 John Wiley & Sons, Ltd.     

Effect of quality control on the proliferation of the extract from Taraxacum mongolicum Hand.‐Mazz. in Lactobacillus plantarum

In recent years, the fingerprint of high‐performance liquid chromatography has been extensively applied in the identification and quality control of traditional Chinese medicine. It can be a potential protocol for assessing the authenticity, stability and consistency of traditional Chinese medicine and guaranteeing the expected biological activity. In this paper, a method using high‐performance liquid chromatography to identify and control the quality of the extract of Taraxacum mongolicum Hand.‐Mazz. (TME) was established. With this method, the correlation coefficients of the similarity of 10 batches were ≥0.994. The TME displayed a steady proliferative effect in Lactobacillus plantarum. In brief, this study successfully built a reliable, simple and efficient method to control and confirm the quality and the stability of biological activity of the TME.     

Adaptive ANOVA decomposition of stochastic incompressible and compressible flows

Realistic representation of stochastic inputs associated with various sources of uncertainty in the simulation of fluid flows leads to high dimensional representations that are computationally prohibitive. We investigate the use of adaptive ANOVA decomposition as an effective dimension–reduction technique in modeling steady incompressible and compressible flows with nominal dimension of random space up to 100. We present three different adaptivity criteria and compare the adaptive ANOVA method against sparse grid, Monte Carlo and quasi-Monte Carlo methods to evaluate its relative efficiency and accuracy. For the incompressible flow problem, the effect of random temperature boundary conditions (modeled as high-dimensional stochastic processes) on the Nusselt number is investigated for different values of correlation length. For the compressible flow, the effects of random geometric perturbations (simulating random roughness) on the scattering of a strong shock wave is investigated both analytically and numerically. A probabilistic collocation method is combined with adaptive ANOVA to obtain both incompressible and compressible flow solutions. We demonstrate that for both cases even draconian truncations of the ANOVA expansion lead to accurate solutions with a speed-up factor of three orders of magnitude compared to Monte Carlo and at least one order of magnitude compared to sparse grids for comparable accuracy.