2-Substituted thiazole-4-carboxamide derivatives as tiazofurin mimics: synthesis and in vitro antitumour activity

Tiazofurin analogues bearing a 5-hydroxymethyl-2-methyl-tetrahydrofuro[2,3-d][1,3]dioxol-6-ol moiety as a sugar mimic (2 and 3), and two novel thiazole-based acyclo-C-nucleosides 4 and 16 have been synthesized in multistep sequences starting from d-xylose (compounds 2 and 3) or from d-arabinose (compounds 4 and 16). All synthesized analogues showed potent in vitro antitumour activities against a panel of human tumour cell lines. Flow cytometry data suggest that cytotoxic effects of analogues 2–4 and 16 in the culture of K562 cells might be mediated by apoptosis. It was also found that these analogues induced changes in cell cycle distribution of K562 cells. Results of western blot analysis (upregulation of Bax and downregulation of Bcl-2, activation of caspase-3 and the presence of a PARP cleavage product) suggest that tiazofurin mimics (2–4 and 16) in K562 cells induced apoptosis in a caspase-dependent way.     

Stereoselective synthesis of erythro-β-chloroamines and their conversion into functionalized trans-oxazolidin-2-ones

New erythro-β-chloroamines were synthesized by a mild and efficient stereoselective chlorination of unprotected amino alcohol diesters. These products are shown to be excellent building blocks for the synthesis of new substituted trans-oxazolidin-2-ones.     

Stereoselective hydrogenation of methylcyclohex-2-ene-1,4-diols used in the synthesis of ampelomins and deoxy-carbasugars

Stereoselective hydrogenation of methylcyclohex-2-ene-1,4-diols used as important intermediates for the preparation of ampelomins and deoxy-carbasugars was studied. These olefins were obtained in few steps from a chiral cis-diol resulting from microbial oxidation of toluene. Although the stereoselective hydrogenation of this type of substrates is difficult, high yields were obtained for heterogeneous hydrogenation using Adam’s catalyst, where steric hindrance controlled the stereochemical outcome of the process. On the other hand, for homogeneous hydrogenation of similar olefins using Crabtree’s catalyst, coordination with the allylic alcohols allowed for a controlled hydrogen addition from the more hindered face. In this manner two protocols for the hydrogenation of these types of substrates resulting in complementary stereoselectivities are described.     

Reduction of nitrobenzene derivatives using sodium borohydride and transition metal sulfides

Reported here is the reduction of aromatic nitro compounds using sodium borohydride and transition metal sulfides as catalysts. The reaction conditions were optimized using the reduction of nitrobenzene as a model reaction. The catalysts studied were iron sulfide (Fe₃S₄), copper sulfide (CuS), zinc sulfide (ZnS), cobalt sulfide (Co₃S₄), and nickel sulfide (NiS). The reduction was monitored using gas chromatography. Quantitative conversions were achieved using Co₃S₄ and NiS, representing a ten-fold increase in reactivity compared to the non-catalyzed reaction. Fe₃S₄ and ZnS had no apparent effect on the reduction of nitrobenzene while the reduction using CuS showed a marginal increase. The reduction method was applied to several aryl-nitro derivatives containing either electron-withdrawing or electron-donating groups. Halogen containing aryl-nitro compounds were reduced without dehalogenation. The reduction had no effect on other functional groups such as carboxylic acids, esters, amides, or alkenes, indicating that the reduction is highly chemoselective.     

Comprehensive two‐dimensional gas chromatography coupled with static headspace sampling to analyze volatile compounds: Application to almonds

The hyphenation of static headspace sampling with comprehensive 2D GC equipped with a modulator based on capillary flow technology and a flame ionization detector was used to separate and identify 43 representative target volatile compounds (light hydrocarbons, carbonyls, pyrazines, alcohols, furans, and benzenes) frequently detected in the roasting process of nuts. Five column combinations with differing degrees of orthogonality (one conventional and four inverted phase sets) were tested in order to obtain the best conditions for analyzing these volatile compounds. Optimization of the working conditions for each of the different column combinations was performed by means of a central composite design. The best results in terms of separation and differentiation among the different chemical groups were achieved with a combination of inverted phase columns (first dimension: highly polar, INNOWax; second dimension: mid‐polar, ZB‐35). Additionally, a reference template was developed to provide an effective and rapid analysis of the target compounds. Finally, the proposed method was successfully employed to identify volatile compounds in raw and roasted almond samples from the Spanish cultivar Largueta.     

Ionic liquids as stationary phases in gas chromatography: Determination of chlorobenzenes in soils

The present research focuses on the evaluation of different ionic liquid (IL) stationary phases in gas chromatography. The different IL columns were evaluated in terms of peak resolution (R_s) and peak symmetry for the separation of the chlorobenzenes. The determination of chlorobenzenes in soil samples by means of the optimal IL stationary phase (SLB‐IL82) is proposed as an application. Soil pretreatment was based on a simplified quick, easy, cheap, effective, rugged, and safe extraction procedure and a large injection volume via a programed temperature vaporizer working in solvent vent mode. The retention time of the chlorobenzenes increased as the polarity of the IL column decreased. SLB‐IL82 is the stationary phase that provides the best values as regards R_s and asymmetry factor. Soil sample blanks were spiked with the analytes before subjecting the sample to the extraction process. The existence of a matrix effect was checked and the analytical characteristics of the method were determined in a fortified garden soil sample. The method provided good linearity, good repeatability and reproducibility values, and the LODs were in the 0.1–4.7 μg/kg range. Two fortified soil samples were applied to validate the proposed methodology.     

Multiresidue analysis of quinolones in water by ultra‐high perfomance liquid chromatography with tandem mass spectrometry using a simple and effective sample treatment

A rapid and simple analytical method has been developed for the determination of 19 quinolones in environmental water samples using ultra high performance liquid chromatography with tandem mass spectrometry. Chromatographic and detection conditions have been optimized and the separation was achieved in less than 4 min. The separation was carried out using a new‐generation column filled with superficially porous particles, resulting in lower backpressure and better resolution than totally porous particle columns. The quinolones were detected by electrospray ionization in positive mode using multiple‐reaction monitoring mode for acquisition. A sample treatment based on liquid–liquid extraction and phase separation via salting‐out was employed to achieve a fast and simple extraction that enables the multiresidue analysis. The method has been validated for an environmental well water sample from a mountain area. Very low limits of detection (between 10 and 90 ng/L) with relative standard deviations lower than 16.5% and recoveries higher than 73% were achieved. Moreover, well waters from different origins (mountain and coast areas and irrigated land) have been evaluated and similar results were obtained.     

Simultaneous determination of pharmaceuticals and some of their metabolites in wastewaters by high performance liquid chromatography with tandem mass spectrometry

The present work describes the development of a sensitive and reliable analytical method based on solid‐phase extraction followed by analysis using liquid chromatography with tandem mass spectrometry for the simultaneous determination of pharmaceuticals from antibiotics (fluoroquinolones, sulfonamides, and their N⁴‐acetyl metabolites, and trimethoprim as sulfonamides synergist) and anthelmintics groups. SPE was optimized using different cartridges (Strata‐X, Oasis HLB, Strata C₁₈‐E, Isolute C₁₈, SampliQ C₈/Si‐SCX). The highest recovery was achieved using Strata X cartridge (>80%) with good reproducibility (RSDs < 5%) despite various physicochemical properties of the compounds. Investigated analytes were identified and quantitatively determined by liquid chromatography with tandem mass spectrometry using multiple reaction monitoring. The method was shown to be linear over the concentration range of 0.05–30 μg/L for febantel and albendazole, and 0.10–60 μg/L for all other pharmaceuticals. Correlation coefficients were >0.99 for all compounds except for sulfamethazine (0.98). In order to demonstrate the applicability of the developed method, wastewater from the veterinary industry was analyzed. Results evidenced the presence of febantel, praziquantel, albendazole, enrofloxacin, sulfamethazine, and sulfadiazine.     

Bovine lactoferrin purification from whey using Yellow HE‐4R as the chromatographic affinity ligand

The worldwide production of whey increases by around 186 million tons each year and it is generally considered as a waste, even when several whey proteins have important economic relevance. For its valorization, inexpensive ligands and integrated chromatography methods need to be developed for specific and low‐cost protein purification. Here, we describe a novel affinity process with the dye Yellow HE‐4R immobilized on Sepharose for bovine lactoferrin purification. This approach based on a low‐cost ligand showed an efficient performance for the recovery and purification of bovine lactoferrin directly from whey, with a yield of 71% and a purification factor of 61.     

Retention behavior of a homologous series and positional isomers of aliphatic amino acids in hydrophilic interaction chromatography

The retention behavior of several series of free α‐ and ω‐amino acids and positional isomers of amino pentanoic acid in the hydrophilic interaction chromatography mode (HILIC) was studied. The study was carried out on three stationary phases followed by post‐column derivatization with fluorescence detection in order to describe the retention mechanism of the tested amino acids. The effect of chromatographic conditions including acetonitrile content in the mobile phase, mobile phase pH (ranging from 3.5 to 6.5) and concentration of buffer in the mobile phase was investigated. The effect of the number of carbon atoms (n_C) in aliphatic chains of the individual homologue of α‐ and ω‐amino acids and the logarithm of the partition coefficient (logD) on retention was also a part of the presented study. A good correlation (r > 0.98) between the logk and logD values of amino acids or n_C, respectively, was observed. The described linear relationships were subsequently applied to predict the retention behavior of individual members of the homologous series of amino acids and to optimize the mobile phase composition in HILIC. The obtained results confirmed that the retention mechanism of α‐amino acids, ω‐amino acids and positional isomers of amino acids was based on the logD values and the number of carbon atoms in the aliphatic chains of amino acids. The elution order of ω‐amino acids and positional isomers of amino pentanoic acid was strongly dependent on the mobile phase pH in the investigated range whereas the retention factors of all α‐amino acids remained essentially unchanged on all tested stationary phases.