Highly Enantioselective Construction of Tricyclic Derivatives by the Desymmetrization of Cyclohexadienones

The asymmetric synthesis of tricyclic compounds by the desymmetrization of cyclohexadienones is presented. The reaction tolerated a large variety of substituents at different positions of the cyclohexadienone, and heterocyclic rings of different sizes were accessible. Density functional theory calculations showed that the reaction proceeds through an asynchronous [4+2] cycloaddition.     

Chemical Probes for the Functionalization of Polyketide Intermediates

A library of functionalized chemical probes capable of reacting with ketosynthase‐bound biosynthetic intermediates was prepared and utilized to explore in vivo polyketide diversification. Fermentation of ACP mutants of S. lasaliensis in the presence of the probes generated a range of unnatural polyketide derivatives, including novel putative lasalocid A derivatives characterized by variable aryl ketone moieties and linear polyketide chains (bearing alkyne/azide handles and fluorine) flanking the polyether scaffold. By providing direct information on microorganism tolerance and enzyme processing of unnatural malonyl‐ACP analogues, as well as on the amenability of unnatural polyketides to further structural modifications, the chemical probes constitute invaluable tools for the development of novel mutasynthesis and synthetic biology.     

Isothermal Titration Calorimetry Study of a Bistable Supramolecular System: Reversible Complexation of Cryptand[2.2.2] with Potassium Ions

Isothermal titration calorimetry (ITC) is used to investigate the thermodynamics of the complexation of potassium ions by 1,10‐diaza‐4,7,13,16,21,24‐hexaoxabicyclo[8.8.8]hexacosane (cryptand[2.2.2]) in aqueous solution. By changing the pH of the solution it was possible to trigger the reversible complexation/decomplexation of the cryptand in consecutive in situ experiments and to assess for the first time the use of ITC to monitor the thermodynamics of a bistable system.     

Enzymatic synthesis of a chiral chalcogran intermediate

Two lipases, Novozyme 435 (lipase B from Candida Antarctica) and Lipozyme TL IM (Thermomyces lanuginosus) were used successfully for the kinetic resolution of racemic 1-(2-furyl)-3-pentanol, the key intermediate in synthesis of the bark beetle pheromone, chalcogran. The desired S-(+)-enantiomer was prepared in enantiomeric excesses higher than 98 % and with yields of 26.3 % and 32.5 %, respectively. Methyl tert-butyl ether and vinyl acetate were found to be the best reaction media and the acetyl donor to achieve fast and effective resolution.     

Photodynamic Activity on Biofilm in Endotracheal Tubes of Patients Admitted to an Intensive Care Unit

Ventilator-associated pneumonia (VAP) is an infection that arises after endotracheal intubation affecting patients under intensive care. The presence of the endotracheal tube (ETT) is a risk factor since it is colonized by multispecies biofilm. Antimicrobial photodynamic therapy (aPDT) could be a strategy to decontaminate ETTs. We verify if methylene blue (MB) associated with external illumination of the ETT could be an alternative to destroy biofilm. We performed an in vitro and ex vivo study. In vitro study was performed with P. aeruginosa biofilm grew over ETT for 7 days. After treatment, the surviving cells were cultured for 3 days and the biofilm was analyzed by crystal violet absorbance. Ex vivo study employed ETT obtained from extubated patients. aPDT was performed with MB (100 µm ) and red LED (λ = 640±20 nm). We quantified the biofilm thickness and used scanning electron microscopy and fluorescence technique to verify morphological and functional changes after aPDT. Our results showed that bacteria remain susceptible to aPDT after sequential treatments. We also attested that aPDT can reduce biofilm thickness, disrupt biofilm attachment from ETT surface and kill microbial cells. These data suggest that aPDT should be investigated to decrease VAP incidence via ETT decontamination.     

Saffron: Chemical Composition and Neuroprotective Activity

Crocus sativus L. belongs to the Iridaceae family and it is commonly known as saffron. The different cultures together with the geoclimatic characteristics of the territory determine a different chemical composition that characterizes the final product. This is why a complete knowledge of this product is fundamental, from which more than 150 chemical compounds have been extracted from, but only about one third of them have been identified. The chemical composition of saffron has been studied in relation to its efficacy in coping with neurodegenerative retinal diseases. Accordingly, experimental results provide evidence of a strict correlation between chemical composition and neuroprotective capacity. We found that saffron’s ability to cope with retinal neurodegeneration is related to: (1) the presence of specific crocins and (2) the contribution of other saffron components. We summarize previous evidence and provide original data showing that results obtained both “in vivo” and “in vitro” lead to the same conclusion.     

New 4-(benzotriazol-1-yl)-1,2,3-triazole derivatives

A new 4-(benzotriazol-1-yl)-1,2,3-triazole structure was obtained by the diazotization reaction of either of 1-(2-aminophenyl)-4-carboxamido-5-amino-1H-1,2,3-triazole ( 1c ) or of the corresponding Dimroth isomer 1d . It underwent some common reactions to evaluate its chemical behaviour and structure. An analogous reaction sequence was carried out from the 2-nitro-4-methylphenyl azide, to assign the structure to the nitro derivatives prepared. The structure of the new compounds prepared was confirmed by chemical and spectroscopic methods.     

Characterization of the Phytochemical Composition and Bioactivities of Anacyclus maroccanus Ball. and Anacyclus radiatus Loisel Aerial Parts: Preliminary Evidence for the Possible Development of Moroccan Plants

In the present study, the phytochemical composition and bioactivities of A. maroccanus (AM) and A. radiatus (AR), two ecotypes collected in the Demnate road and Essaouira regions, respectively, were studied to highlight a pharmacological interest and to enable possible pharmaceutical development. To this end, methanolic and ethyl acetate extracts were prepared for each ecotype by fractionation; next, their phytochemical composition was evaluated by spectrophotometric and chromatographic analysis. Moreover, in line with the available evidence for Anacyclus spp. and their traditional use, a screening of bioactivities, including antioxidant, hypoglycemic, antiglycative, chelating, and antibacterial activities, was performed. The extracts were characterized by high amounts of polyphenols, tannins, and flavonoids, especially in the methanolic extracts; these samples were also enriched in carotenoids despite a lower chlorophyll content. Chlorogenic acid and rutin were the major identified compounds. The extracts also showed interesting hypoglycemic, antiglycative, and antibacterial properties, although with differences in efficacy and potency. Present results provide more scientific basis to the ethnopharmacological uses of Anacyclus spp. and suggest a further interest in AM and AR ecotypes as natural sources of bioactive compounds and/or phytocomplexes for possible pharmaceutical and nutraceutical developments.     

Bipolar Electrochemiluminescence Imaging: A Way to Investigate the Passivation of Silicon Surfaces

This work depicts the original combination of electrochemiluminescence (ECL) and bipolar electrochemistry (BPE) to map in real-time the oxidation of silicon in microchannels. We fabricated model silicon-PDMS microfluidic chips, optionally containing a restriction, and monitored the evolution of the surface reactivity using ECL. BPE was used to remotely promote ECL at the silicon surface inside microfluidic channels. The effects of the fluidic design, the applied potential and the resistance of the channel (controlled by the fluidic configuration) on the silicon polarization and oxide formation were investigated. A potential difference down to 6 V was sufficient to induce ECL, which is two orders of magnitude less than in classical BPE configurations. Increasing the resistance of the channel led to an increase in the current passing through the silicon and boosted the intensity of ECL signals. Finally, the possibility of achieving electrochemical reactions at predetermined locations on the microfluidic chip was investigated using a patterning of the silicon oxide surface by etched micrometric squares. This ECL imaging approach opens exciting perspectives for the precise understanding and implementation of electrochemical functionalization on passivating materials. In addition, it may help the development and the design of fully integrated microfluidic biochips paving the way for development of original bioanalytical applications.