The production of enantiomerically pure 1-phenylethanol by enzymatic kinetic resolution method using response surface methodology

As the enantiomers of 1-phenylethanol are valuable intermediates in several industries, the lipase catalyzed kinetic resolution of (R,S) -1-phenylethanol is a relevant research topic. In this study, the goal was to determine the optimum reaction parameters to produce enantiomerically pure 1-phenylethanol by lipase (Novozyme 435) catalyzed kinetic resolution using response surface methodology (RSM). Reactions were performed with 40–400 mM (R,S)-1-phenylethanol, 120–1200 mM vinyl acetate and 2–22 mg/mL biocatalyst concentrations (BC _L ), at 20–60 °C and with a stirring rate of 50–400 rpm for 5–120 min. The samples were analyzed using high performance liquid chromatography (HPLC) with a Chiralcel OB column. Optimum reaction parameters to reach 100% enantiomeric excess for the substrate ( ee _s ) were determined as follows: substrate concentration (C _s ): 240 mM, BC _L : 11 mg/mL, at 42 °C with a reaction time of 75 min. Model validation was performed using these conditions and ee _s was calculated as 100%, which indicates the predicted model was efficient and accurate. When compared to the literature, it was observed that the reaction time decreased significantly. This is an important result considering the industrial scale perspective.     

Protein tyrosine phosphatase 1B inhibitors from a marine-derived fungal strain aspergillus sp. SF-5929

Abstract

In the course of our continuing investigation of bioactive secondary metabolites from marine-derived fungal strains, a racemate of a novel diphenolic derivative named (±)-tylopilusin D (1) along with ten previously known secondary metabolites (2–11) were isolated from a marine-derived fungal strain Aspergillus sp. SF-5929. Their structures were elucidated mainly by analysis of NMR and MS data. In addition, the inhibitory effects of the isolated compounds against protein tyrosine phosphatase 1B (PTP1B) activity were evaluated, and compounds 1, 2, and 5–7 inhibited PTP1B activity with IC₅₀ values ranging from 3.3 to 8.1?µM. Kinetics studies suggested that compounds 1, 2, and 5 had noncompetitive inhibitory effects against PTP1B.     

饮用水中三氯甲烷与其他氯消毒副产物在活性炭上的吸附竞争研究

通过等温吸附实验，探究了三氯甲烷（CHCl₃）与二氯一溴甲烷（CHBrCl₂）、二氯乙酸（Cl₂CHCOOH）在活性炭上的竞争吸附关系，同时探究了在低浓度条件下CHBrCl₂和Cl₂CHCOOH浓度变化对活性炭吸附CHCl₃的影响。实验结果表明，活性炭吸附CHCl₃和CHBrCl₂符合Freundlich模型，对Cl₂CHCOOH的吸附符合Langmuir模型；活性炭对3种消毒副产物均为优先吸附，吸附能力由大到小依次为CHBrCl₂、CHCl₃、Cl₂CHCOOH；低浓度条件下，活性炭对消毒副产物的吸附效果随体系中物质种类的增加而降低；低浓度条件下，Cl₂CHCOOH的浓度变化对CHCl₃的吸附效果影响不大，但吸附效果随水体中CHBrCl₂浓度的升高而降低。     

Development and validation of a reversed‐phase HPLC method for CYP1A2 phenotyping by use of a caffeine metabolite ratio in saliva

CYP1A2 is important for metabolizing various clinically used drugs. Phenotyping of CYP1A2 may prove helpful for drug individualization therapy. Several HPLC methods have been developed for quantification of caffeine metabolites in plasma and urine. Aim of the present study was to develop a valid and simple HPLC method for evaluating CYP1A2 activity during exposure in xenobiotics by the use of human saliva. Caffeine and paraxanthine were isolated from saliva by liquid‐liquid extraction (chlorophorm/isopropanol 85/15v/v). Extracts were analyzed by reversed‐phase HPLC on a C₁₈ column with mobile phase 0.1% acetic acid/methanol/acetonitrile (80/20/2 v/v) and detected at 273nm. Caffeine and paraxanthine elution times were <13min with no interferences from impurities or caffeine metabolites. Detector response was linear (0.10–8.00µg/ml, R²>0.99), recovery was >93% and bias <4.47%. Intra‐ and inter‐day precision was <5.14% (n=6). The limit of quantitation was 0.10µg/ml and the limit of detection was 0.018±0.002µg/mL for paraxanthine and 0.032±0.002µg/ml for caffeine. Paraxanthine/caffeine ratio of 34 healthy volunteers was significantly higher in smokers (p<0.001). Saliva paraxanthine/caffeine ratios and urine metabolite ratios were highly correlated (r=0.85, p<0.001). The method can be used for the monitoring of CYP1A2 activity in clinical practice and in studies relevant to exposure to environmental and pharmacological xenobiotics. Copyright © 2015 John Wiley & Sons, Ltd.     

Synthesis,characterization and α‐amylase and α‐glucosidase inhibition studies of novel vanadyl chalcone complexes

A series of chalcone ligands and their corresponding vanadyl complexes of composition [VO (L^I–IV)₂(H₂O)₂]SO₄ (where L^I = 1,3‐Diphenylprop‐2‐en‐1‐one, L^II = 3‐(2‐Hydroxy‐phenyl)‐1‐phenyl‐propenone, L^III = 3‐(3‐Nitro‐phenyl)‐1‐phenyl‐propenone, L^IV = 3‐(4‐Methoxy‐phenyl)‐1‐phenyl‐propenone) have been synthesized and characterized using various spectroscopic (Fourier‐transform infrared, electrospray ionization mass, nuclear magnetic resonance, electron paramagnetic resonance, thermogravimetric analysis, vibrating sample magnetometer) and physico‐analytic techniques. Antidiabetic activities of synthesized complexes along with chalcones were evaluated by performing in vitro and in silico α‐amylase and α‐glucosidase inhibition studies. The obtained results displayed moderate to significant inhibition activity against both the enzymes by vanadyl chalcone complexes. The most potent complexes were further investigated for the enzyme kinetic studies and displayed the mixed inhibition for both the enzymes. Further, antioxidant activity of vanadyl chalcone complexes was evaluated for their efficiency to release oxidative stress using 2,2‐diphenyl‐1‐picryl‐hydrazyl‐hydrate assay, and two complexes (Complexes 2 and 4 ) have demonstrated remarkable antioxidant activity. All the complexes were found to possess promising antidiabetic and antioxidant potential.     

Palladium‐catalyzed decarboxylative coupling of α,β‐unsaturated carboxylic acids with aryl tosylates

We report a general method for selective cross‐coupling of α,β‐unsaturated carboxylic acids with aryl tosylates enabled by versatile Pd(II) complexes. This method features the general cross‐coupling of ubiquitous α,β‐unsaturated carboxylic acids by decarboxylation. The transformation is characterized by its operational simplicity, the use of inexpensive, air‐stable Pd(II) catalysts, scalability and wide substrate scope. The reaction proceeds with high trans selectivity to furnish valuable (E)‐1,2‐diarylethenes.     

Molecular dynamics of the intramolecular 1, 3-dipolar ene reaction of a nitrile oxide and an alkene: non-statistical behavior of a reaction involving a diradical intermediate*

ABSTRACT

Potential energy surfaces and molecular dynamics of the intramolecular 1, 3-dipolar cycloaddition and ene reaction of a nitrile oxide with an alkene were performed in the gas phase and in dichloromethane with density functional theory. One hundred trajectories were propagated in the gas phase and in dichloromethane, respectively. Twenty percent of the trajectories in the gas phase involve bicyclic intermediate and the mean time gap is 472fs. A dynamically stepwise reaction is observed. In dichloromethane, more reactive trajectories were obtained and the time gap is larger than that in the gas phase.     

Et2Zn-mediated stoichiometric C(sp)-H silylation of 1-alkynes and chlorosilanes

A first example of an Et₂Zn mediated silylation of 1-aklynes is reported. A series of functional groups are tolerated in this reaction. Mechanistic studies support Zn alkynilides as intermediates in the reaction. This reaction protocol provides a practical method for the preparation of alkynylsilanes and expands the application of organometallic zinc in organic synthesis.     

Effect of Zr concentration on the mechanical and thermodynamic properties of NbIr3 intermetallic compounds from theoretical estimations

ABSTRACT

The iridium is an important metal which has excellent resistance to corrosion at high temperature. L1₂ intermetallic compounds i.e. Ir₃Nb and Ir₃Zr, with similar lattice parameters are ideal for working at high temperature. They are fully soluble due to their low lattice misfit. A first-principle investigation into the effect of doping Zr with different concentrations on the electronic structure, mechanical and thermodynamic properties of NbIr₃ has been studied to prompt the development of novel high-temperature materials. Nine Zr_xNb_8?xIr₂₄ compounds are carefully considered. The results show that adding Zr into these compounds can strengthen their structural stability and ductility. Nevertheless, it reduces the elastic modulus and elastic stiffness. Simultaneously, with the increase of Zr content, the thermodynamic properties of these compounds decrease. It is also found that the changes of elastic modulus are mainly attributed to the variations of bonds in these compounds.