Synthesis of 3-substituted 4-piperidinones via a one-pot tandem oxidation-cyclization-oxidation process: stereodivergent reduction to 3,4-disubstituted piperidines

A novel approach to 3-substituted 4-piperidinones is described. The one-pot tandem oxidation-cyclization-oxidation of unsaturated alcohols 1a-e by PCC or PCC and trifluoromethanesulfonic acid affords piperidinones 2a-e in good yield. Reduction of 2a-e by L-Selectride gives the corresponding cis 3,4-disubstituted piperidines with diastereomeric ratios of >99:1. By contrast, reduction of 2a-e by Al-isopropoxydiisobutylalane gives the trans products with diastereomeric ratios of up to 99:1.     

Glutamine: fructose-6-phosphate amidotransferase (GFAT): homology modelling and designing of new inhibitors using pharmacophore and docking based hierarchical virtual screening protocol

Glutamine: fructose-6-phosphate amidotransferase (GFAT), also termed GFPT1 and GFAT1, catalyzes the first committed step of the hexosamine biosynthesis pathway in mammals and consequently plays an important role in type 2 diabetes. In the present study, a combination of pharmacophore modelling, homology modelling, and molecular docking analysis was performed to design new glutamine competitive inhibitors of human GFAT, and to investigate important interaction details of inhibitor molecules. A pharmacophore model of GFAT inhibitors was developed, subsequently validated, and utilized for the screening by the PHASE database to identify new molecules. Afterwards, homology modelling was performed to construct the glutamine-binding site of the GFAT protein. The modelled active site was utilized to dock the studied molecules to investigate important receptor-ligand interactions and to scrutinize database-screened molecules on the basis of essential interactions. This systematic in silico protocol helped us to identify new molecules that would be explored for the treatment of type 2 diabetes and its complications.     

Three Validated Methods for Simultaneous Determination of Ofloxacin and Dexamethasone in Binary Mixture

JPC – Journal of Planar Chromatography – Modern TLC - Three selective, precise, and accurate methods were developed and validated for the simultaneous determination of ofloxacin and...     

Simultaneous Densitometric TLC Analysis of Olmesartan Medoxomil and Hydrochlorothiazide in the Tablet Dosage Form

JPC – Journal of Planar Chromatography – Modern TLC - A simple, rapid, and selective densitometric thin-layer chromatographic (TLC) method has been established and validated for...     

Photon channelling in foams

Experiments by Gittings, Bandyopadhyay and Durian (Europhys. Lett. 65, 414 (2004)) demonstrate that light possesses a higher probability to propagate in the liquid phase of a foam due to total reflection. The authors term this observation photon channelling which we investigate in this article theoretically. We first derive a central relation in the work of Gitting et al. without any free parameters. It links the photon's path-length fraction f in the liquid phase to the liquid fraction ɛ. We then construct two-dimensional Voronoi foams, replace the cell edges by channels to represent the liquid films and simulate photon paths according to the laws of ray optics using transmission and reflection coefficients from Fresnel's formulas. In an exact honeycomb foam, the photons show superdiffusive behavior. It becomes diffusive as soon as disorder is introduced into the foams. The dependence of the diffusion constant on channel width and refractive index is explained by a one-dimensional random-walk model. It contains a photon channelling state that is crucial for the understanding of the numerical results. At the end, we shortly comment on the observation that photon channelling only occurs in a finite range of ɛ.     

Chemical composition of the essential oil of Pituranthos scoparius

The essential oils obtained by hydro distillation of the aerial parts of Pituranthos scoparius were collected from different regions of Algeria and gave various yields ranging from 0.6 up to 2.8% (v/w). These samples were analyzed by GC and GC-MS showing the occurrence of monoterpene hydrocarbons and some oxygenated compounds. The major components were alpha-pinene (4.4-35.8%), limonene (0.8-66.5%), bornyl acetate (tr-9.6%), myristicin (tr-31.1) and dill apiole (0.4-47.3%). The aerial parts of P. scoparius could be either very rich or very poor in limonene, myristicin or dill apiole. Cluster analysis shows differences in essential oil compositions of samples coming from the different area collected.     

Multivariate optimization of a GC-MS method for determination of sixteen priority polycyclic aromatic hydrocarbons in environmental samples

This paper describes the development and optimization, by using multivariate analysis, of a GC-MS-SIM method for evaluation of the 16 polyaromatic hydrocarbons considered as priority pollutants in atmospheric particulate material by the US EPA. In order to assure an adequate separation in the shortest analysis time, a multivariate design was used to set the conditions of the oven temperature program. The optimization process was carried out using factorial fractional design and Box-Behnken design. The following factors were evaluated: initial temperature, temperature rate #1, intermediary temperature, temperature rate #2, and final temperature. The optimized conditions were set at: 70 degrees C (2 min) --> 200 degrees C (30 degrees C/min, 5 min) --> 300 degrees C (5 degrees C/min, 1.67 min). Moreover, we have also optimized the injector temperature as 310 degrees C and sampling time as 0.8 min. The total analysis time was 33 min. Validation of GC-MS-SIM yielded satisfactory results for repetitivity of the detector response and retention times, and linearity of calibration curves. LOD were established as 0.13-0.34 ng/mL (peak area) and 0.18-0.72 ng/mL (peak height). The method has been shown to be appropriate for the analysis of samples of atmospheric particulate material and/or other environmental matrices.     

High precision delta(17)O isotope measurements of oxygen from silicates and other oxides: method and applications

The use of infrared laser-assisted fluorination to release oxygen from milligram quantities of silicates or other oxide mineral grains is a well-established technique. However, relatively few studies have reported the optimisation of this procedure for oxygen-17 isotope measurements. We describe here details of an analytical system using infrared (10 μm) laser-assisted fluorination, in conjunction with a dual inlet mass spectrometer of high resolving power ( approximately 250) to provide (17)O and (18)O oxygen isotope measurements from 0.5-2 mg of silicates or other oxide mineral grains. Respective precisions (1) of typically 0.08 and 0.04 per thousand are obtained for the complete analytical procedure. Departures from the mass-dependent oxygen isotope fractionation line are quantified by Delta(17)O; our precision (1) of such measurements on individual samples is shown to be +/-0.024 per thousand. In turn, this permits the offset between parallel, mass-dependent fractionation lines to be characterised to substantially greater precision than has been possible hitherto. Application of this system to investigate the (17)O versus (18)O relationship for numerous terrestrial whole-rock and mineral samples, of diverse geological origins and age, indicates that the complete data set may be described by a single, mass-dependent fractionation line of slope 0.5244+/- 0.00038 (standard error). Copyright 1999 John Wiley & Sons, Ltd.     

Copper and iron interactions with angiotensin-converting enzyme inhibitors. A study by fast-atom bombardment tandem mass spectrometry

Fast atom bombardment, combined with high-energy collision-induced tandem mass spectrometry, has been used to investigate gas-phase metal-ion interactions with captopril, enalaprilat and lisinopril, all angiotensin-converting enzyme inhibitors.Suggestions for the location of metal-binding sites are presented. For captopril, metal binding occurs most likely at both the sulphur and the nitrogen atom. For enalaprilat and lisinopril, binding preferably occurs at the amine nitrogen. Copyright 1999 John Wiley & Sons, Ltd.     

A validated RP‐HPLC method for the evaluation of the influence of grapefruit juice on liver S9 activation of sacubitril

Grapefruit juice inhibits esterase enzyme. Therefore, a possible interaction with ester prodrugs should be taken into consideration. In this study, the influence of grapefruit juice on sacubitril (SAC) rat liver S9 activation by esterase enzyme was evaluated. An RP‐HPLC method was developed and validated for estimation of SAC in rat liver S9 fraction using a C₁₈ Cyano column as stationary phase and acetonitrile–sodium di‐hydrogen phosphate buffer (0.02 m , pH 4 adjusted by o‐phosphoric acid, 40:60, v/v), as mobile phase at a flow rate of 1 mL/min and UV detection at 254 nm. The method was successfully applied to an in vitro study in which SAC was incubated with rat liver S9 fraction prepared from rats that had previously ingested grapefruit juice for a week. The calculated SAC concentration after incubation was compared with that of SAC incubated with rat liver S9 fraction from the rat control group. The statistical significance between the results of test and control incubation sets was assessed. In conclusion, the current study demonstrated that grapefruit juice decreased SAC hydrolysis, hence delaying its activation to sacubitrilat (active form) in gut lumen. Based on this food–drug interaction, it may be required that grapefruit juice should be consumed with caution in patients receiving SAC.