A catalytic domino reduction–imine formation–intramolecular cyclization–oxidation for the general synthesis of a wide variety of biologically relevant N‐polyheterocycles, such as quinoxaline‐ and ...quinoline‐fused derivatives, and phenanthridines, is reported. A simple, easily available, and environmentally friendly dioxomolybdenum(VI) complex has proven to be a highly efficient and versatile catalyst for transforming a broad range of starting nitroarenes involving several redox processes. Not only is this a sustainable, step‐economical as well as air‐ and moisture‐tolerant method, but also it is worth highlighting that the waste byproduct generated in the first step of the sequence is recycled and incorporated in the final target molecule, improving the overall synthetic efficiency. Moreover, selected indoloquinoxalines have been photophysically characterized in cyclohexane and toluene with exceptional fluorescence quantum yields above 0.7 for the alkyl derivatives.
A catalytic domino reduction / imine formation / intramolecular cyclization / oxidation allows the synthesis of a wide variety of biologically relevant N‐polyheterocycles. The reported process employs an inexpensive and nontoxic dioxomolybdenum(VI) complex as catalyst, easily available nitroarenes as starting materials and different glycols as reducing agents with reuse of the waste reduction carbonyl byproduct, which is embodied into the final compounds.
A general catalytic system for the coupling of aryl halides and sulfonates with thiols based on the use of the CyPF-t-Bu ligand (1) is reported. The reactions catalyzed by complexes of 1 occur in ...excellent yields with broad scope and exhibit extraordinary turnover numbers and high tolerance of functional groups. Turnover numbers usually exceed those of previous catalysts by 2 or 3 orders of magnitude. In addition, the reactions of aryl tosylates with alkane thiols to form aryl sulfides are reported for the first time. Finally, the synthesis of a diarylsulfide from two bromoarenes was accomplished using a hydrogen sulfide surrogate.
Indenes and related polycyclic structures have been efficiently synthesized by gold(I)‐catalyzed cycloisomerizations of appropriate ortho‐(alkynyl)styrenes. Disubstitution at the terminal position of ...the olefin was demonstrated to be essential to obtain products originating from a formal 5‐endo‐dig cyclization. Interestingly, a complete switch in the selectivity of the cyclization of o‐(alkynyl)‐α‐methylstyrenes from 6‐endo to 5‐endo was observed by adding an alcohol to the reaction media. This allowed the synthesis of interesting indenes bearing an all‐carbon quaternary center at C1. Moreover, dihydrobenzoafluorenes can be obtained from substrates bearing a secondary alkyl group at the β‐position of the styrene moiety by a tandem cycloisomerization/1,2‐hydride migration process. In addition, diverse polycyclic compounds were obtained by an intramolecular gold‐catalyzed alkoxycyclization of o‐(alkynyl)styrenes bearing a nucleophile in their structure. Finally, the use of a chiral gold complex allowed access to elusive chiral 1H‐indenes in good enantioselectivities.
Going for gold! A full account for the gold(I)‐catalyzed reactions of ortho‐(alkynyl)styrenes is reported. Selective 5‐endo cyclizations are achieved by control of substrate olefin substitution patterns, which give rise to a wide variety of interesting 1H‐indenes (see scheme). These compounds can be prepared in an enantioselective way by using a chiral gold complex.
Spanish legislation regulates the labelling of Iberian pig meat and dry-cured products, which are labelled as “Ibérico” or “100% Ibérico” when they come from Duroc x Iberian crossbred or Iberian ...purebred pigs. Although the analytical authentication of breed origin is not mandatory, a genetic diagnostic tool is demanded by producers and consumers. We have designed a 64 Single Nucleotide Variant genotyping panel displaying extreme allelic frequencies between Duroc and Iberian purebred samples. Average proportions of Iberian alleles of 0.99, 0.01, 0.77 and 0.48 were estimated by admixture clustering analysis of known origin samples, for Iberian and Duroc purebred, 75% Iberian and 50% Iberian classes, respectively. A supervised analysis with 1419 samples showed some overlapping between contiguous classes, but the calculated degrees of separability ranged from 0.800 to 0.996, exceeding the threshold value (0.70) for considering suitable for prediction. Therefore, this panel is a useful genetic tool to infer purebred or crossbred Iberian origin of live animals, meat and dry-cured products.
Push‐pull alkynylcyclopropane derivatives are claimed as suitable and active substrates for gold‐catalyzed transformations. Thus, 2(3H)‐azepinones can be readily prepared from ...alkynylcyclopropanecarboxamides through a nucleophilic addition/cyclopropane ring‐opening cascade process and, in this manuscript, the scope and the limitations of such reaction sequence are reported. The cascade reaction is general and occurs with complete regio‐ and quimioselection to form the seven‐membered heterocycles with the exception of primary alkyl‐substituted alkynylcyclopropanecarboxamides that render 4‐methoxy‐6‐oxo‐4‐enenitriles in moderate yields. Additionally, less activated alkynylcyclopropylmethanols undergo regioselective cycloisomerization at low temperature leading to oxabicyclo4.1.0heptanes. Notably, the cyclopropane ring opening of these adducts takes place under thermal conditions to form dihydropyranones.
This study evaluates the effectiveness of adding a diet smartphone application to standard counseling to modify dietary composition over the long term (12 months).
A randomized, controlled, ...multicenter clinical trial was conducted involving the participation of 833 subjects from primary care clinics (415 to the intervention (counseling + application) group (IG) and 418 to the control (counseling) group (CG)). Both groups were counseled about a healthy diet and physical activity. For the 3-month intervention period, the IG was also trained to use a diet smartphone application that involved dietary self-monitoring and tailored feedback. Nutritional composition was estimated using a self-reported food frequency questionnaire.
An analysis of repeated measures revealed an interaction between the group and the percentages of carbohydrates (
= 0.031), fats (
= 0.015) and saturated fats (
= 0.035) consumed. Both groups decreased their energy intake (Kcal) at 12 months (IG: -114 (95% CI: -191 to -36); CG: -108 (95% CI: -184 to -31)). The IG reported a higher percentage intake of carbohydrates (1.1%; 95% CI: 0.1 to 2.0), and lower percentage intakes of fats (-1.0%; 95% CI: -1.9 to -0.1) and saturated fats (-0.4%; 95%CI: -0.8 to -0.1) when compared to the CG.
Better results were achieved in terms of modifying usual diet composition from counseling and the diet smartphone application compared to counseling alone. This was evaluated by a self-reported questionnaire, which indicated an increased percentage intake of carbohydrates, and decreased percentage intakes of fats and saturated fats.
In this work, we show the advantages of label-free, tridimensional mass spectrometry imaging using dual beam analysis (25 keV Bi
3
+
) and depth profiling (20 keV with a distribution centered at Ar
...1500
+
) coupled to time of flight secondary ion mass spectrometry (3D-MSI-TOF-SIMS) for the study of A-172 human glioblastoma cell line treated with B-cell lymphoma 2 (Bcl-2) inhibitor ABT-737. The high spatial (~250 nm) and high mass resolution (m/Δm ~10,000) of TOF-SIMS permitted the localization and identification of the intact, unlabeled drug molecular ion (
m/z
811.26 C
42
H
44
ClN
6
O
5
S
2
–
M – H
–
) as well as characteristic fragment ions. We propose a novel approach based on the inspection of the drug secondary ion yield, which showed a good correlation with the drug concentration during cell treatment at therapeutic dosages (0–200 μM with 4 h incubation). Chemical maps using endogenous molecular markers showed that the ABT-737 is mainly localized in subsurface regions and absent in the nucleus. A semiquantitative workflow is proposed to account for the biological cell diversity based on the spatial distribution of endogenous molecular markers (e.g., nuclei and cytoplasm) and secondary ion confirmation based on the ratio of drug-specific fragments to molecular ion as a function of the therapeutic dosage.
Graphical Abstract
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We carried out a study to investigate the associations between mitochondrial DNA polymorphisms and meat quality traits (intramuscular fat and protein content of the longissimus) in an Iberian porcine ...line named Torbiscal. The studied pigs (n = 319) belong to 9 maternal lineages and were previously assigned to 6 mitochondrial haplotypes (H1 to H6), based on Cytochrome b and Dloop sequences. Statistical analyses, following a bivariate mixed model, show a greater fat content and lower protein content in H3 haplotype carriers than H1, H2, H4, H5, and H6 haplotype carriers. The magnitudes of these differences are close to 1 g of fat and -0.5 g of protein per 100 g of muscle. To identify the causative mutation of these effects on intramuscular fat and protein contents, the complete mitochondrial DNA sequence of 6 individuals was determined, each one carrying a different mitochondrial haplotype. The alignments of these 6 complete mitochondrial sequences allowed identification of 32 substitutions and 2 indels. Two polymorphic positions were exclusively detected in H3 carriers: a synonymous transition 9104C > T in the gene-coding region of Cytochrome c oxidase subunit III and a substitution 715A > G in 12S rRNA. Genotyping results of a larger number of Torbiscal samples showed the exclusive presence of 9104T and 715G alleles in H3 carriers. The detected candidate substitutions are located in essential mitochondrial genes, and although they do not change the amino acid composition, we cannot disregard a potential change in the secondary structure of their corresponding mRNA. The usefulness of these polymorphisms as markers in selection programs requires validation of the consistency of these results in other Iberian pig lines.
Metal‐free borylative cyclization of biphenyl‐embedded 1,3,5‐trien‐7‐ynes in the presence of simple and inexpensive BCl3 provided synthetically useful borylated building blocks. The outcome of the ...process depends on the reaction temperature, with borylated phenanthrenes obtained at 60 °C and phenanthrene‐fused borylated cyclobutanes formed at 0 °C. Based on DFT calculations, a mechanism for these novel transformations has been proposed, which involves an uncommon skeletal rearrangement, including migration of a methyl group and alkyne fragmentation, unprecedented in BCl3‐promoted cyclization reactions.
Metal‐free borylative cyclization reactions of 1,3,5‐trien‐7‐ynes provide straightforward access to polycyclic borylated building blocks. Depending on the temperature, either phenanthrenes (at 60 °C) or phenanthrene‐fused cyclobutanes (at 0 °C) can be obtained selectively. The reaction at 60 °C proceeds through an unusual skeletal rearrangement unprecedented in BCl3‐promoted cyclizations.
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