Chlorogenic acids (CGAs) have gained considerable attention as pervasive human dietary constituents with potential cardiovascular-preserving effects. The main sources include coffee, yerba mate,
...leaves, and Lonicerae Japonicae Flos. CGA consumption can reduce the risks of hypertension, atherosclerosis, heart failure, myocardial infarction, and other factors associated with cardiovascular risk, such as obesity and type 2 diabetes. This review recapitulates recent advances of CGAs in the cardiovascular-preserving effects, pharmacokinetics, sources, and safety. Emerging evidence indicates that CGAs exhibit circulatory guarding properties through the suppression of oxidative stress, leukocyte infiltration, platelet aggregation, platelet-leukocyte interactions, vascular remodeling, and apoptosis as well as the regulation of glucose and lipid metabolism and vasodilatory action in the cardiovascular system. CGAs exert these effects by acting on complex signaling networks, but the global mechanisms are still not clear. The oral bioavailability of CGA is poor, and there is a potential sensitization concern about CGA. The bioactive metabolites, systematic toxicity, and optimized structure are needed for further identification.
Aiming at the problem of prediction accuracy of stochastic volatility series, this paper proposes a method to optimize the grey model(GM(1,1)) from the perspective of residual error. In this study, a ...new fitting method is firstly used, which combines the wavelet function basis and the least square method to fit the residual data of the true value and the predicted value of the grey model(GM(1,1)). The residual prediction function is constructed by using the fitting method. Then, the prediction function of the grey model(GM(1,1)) is modified by the residual prediction function. Finally, an example of the wavelet residual-corrected grey prediction model (WGM) is obtained. The test results show that the fitting accuracy of the wavelet residual-corrected grey prediction model has irreplaceable advantages.
Abstract
Biobased thermoplastic polyamide elastomers (TPAEs) have received increasing attention in both academia and industry. Here, a series of semi‐biobased long‐chain TPAEs are successfully ...synthesized via one‐step melt polymerization, employing polyamide 1210 (PA1210) and polyetheramines (PEAs) as hard and soft segments, respectively. The prepared TPAEs demonstrate excellent mechanical properties, energy dissipation capabilities, low density, good damping, high resilience, and low melting temperature. More interestingly, the properties of the TPAEs can be customized by adjusting the content and molecular weight of PEA. By varying the molecular weights of the PEAs, two different thermal behaviors can be observed in the prepared TPAEs. Specifically, PEA with low molecular weight has good compatibility with PA1210, leading to an increase in the conformation of the crystalline region and a significant decrease in melting temperature. Meanwhile, high molecular weight PEA causes strong phase separation with PA1210, leading to limited crystalline regions and inadequate physical cross‐linking, further resulting in suboptimal mechanical properties. This work provides new insights into the design and preparation of PEA‐type biobased long‐chain TPAEs.
Site-selective functionalization of C-H bonds will ultimately afford chemists transformative tools for editing and constructing complex molecular architectures. Towards this goal, it is essential to ...develop strategies to activate C-H bonds that are distal from a functional group. In this context, distinguishing remote C-H bonds on adjacent carbon atoms is an extraordinary challenge due to the lack of electronic or steric bias between the two positions. Herein, we report the design of a catalytic system leveraging a remote directing template and a transient norbornene mediator to selectively activate a previously inaccessible remote C-H bond that is one bond further away. The generality of this approach has been demonstrated with a range of heterocycles, including a complex anti-leukaemia agent and hydrocinnamic acid substrates.
The CRISPR RNA-guided Cas9 nuclease gene-targeting system has been successfully used for genome editing in a variety of organisms. Here, we report the use of dual sgRNA-guided Cas9 nuclease to ...generate knockout mutants of protein coding genes, noncoding genes, and repetitive sequences in C. elegans. Co-injection of C. elegans with dual sgRNAs results in the removal of the interval between two sgRNAs and the loss-of-function phenotype of targeted genes. We sought to determine how large an interval can be eliminated and found that at least a 24 kb chromosome segment can be deleted using this dual sgRNA/Cas9 strategy. The deletion of large chromosome segments facilitates mutant screening by PCR and agarose electrophoresis. Thus, the use of the CRISPR/Cas9 system in combination with dual sgRNAs provides a powerful platform with which to easily generate gene knockout mutants in C. elegans. Our data also suggest that encoding multiple sgRNA sequences into a single CRISPR array to simultaneously edit several sites within the genome may cause the off-target deletion of chromosome sequences.
Metal‐Free Directed C−H Borylation of Pyrroles Wang, Zheng‐Jun; Chen, Xiangyang; Wu, Lei ...
Angewandte Chemie International Edition,
April 6, 2021, Letnik:
60, Številka:
15
Journal Article
Recenzirano
Robust strategies to enable the rapid construction of complex organoboronates in selective, practical, low‐cost, and environmentally friendly modes remain conspicuously underdeveloped. Here, we ...develop a general strategy for the site‐selective C−H borylation of pyrroles by using only BBr3 directed by pivaloyl groups, avoiding the use of any metal. The site‐selectivity is generally dominated by chelation and electronic effects, thus forming diverse C2‐borylated pyrroles against the steric effect. The formed products can readily engage in downstream transformations, enabling a step‐economic process to access drugs such as Lipitor. DFT calculations (wB97X‐D) demonstrate the preferred positional selectivity of this reaction.
An efficient metal‐free system has been uncovered for the site‐selective C−H borylation of pyrroles by using only BBr3 directed by pivaloyl groups. The site‐selectivity is generally dominated by chelation and electronic effects, thus forming diverse C2‐borylated pyrroles against the steric effect.
Many genes play essential roles in development and fertility; their disruption leads to growth arrest or sterility. Genetic balancers have been widely used to study essential genes in many organisms. ...However, it is technically challenging and laborious to generate and maintain the loss-of-function mutations of essential genes. The CRISPR/Cas9 technology has been successfully applied for gene editing and chromosome engineering. Here, we have developed a method to induce chromosomal translocations and produce genetic balancers using the CRISPR/Cas9 technology and have applied this approach to edit essential genes in Caenorhabditis elegans. The co-injection of dual small guide RNA targeting genes on different chromosomes resulted in reciprocal translocation between nonhomologous chromosomes. These animals with chromosomal translocations were subsequently crossed with animals that contain normal sets of chromosomes. The F1 progeny were subjected to a second round of Cas9-mediated gene editing. Through this method, we successfully produced nematode strains with specified chromosomal translocations and generated a number of loss-of-function alleles of two essential genes (csr-1 and mes-6). Therefore, our method provides an easy and efficient approach to generate and maintain loss-of-function alleles of essential genes with detailed genetic background information.
Prized for their ability to generate chemical complexity rapidly, catalytic carbon-hydrogen (C-H) activation and functionalization reactions have enabled a paradigm shift in the standard logic of ...synthetic chemistry. Directing group strategies have been used extensively in C-H activation reactions to control regio- and enantioselectivity with transition metal catalysts. However, current methods rely heavily on coordination with nitrogen and/or oxygen atoms in molecules and have therefore been found to exhibit limited generality in asymmetric syntheses. Here, we report enantioselective C-H activation with unsaturated hydrocarbons directed by phosphorus centres to rapidly construct libraries of axially chiral phosphines through dynamic kinetic resolution. High reactivity and enantioselectivity are derived from modular assembly of an iridium catalyst with an endogenous phosphorus atom and an exogenous chiral phosphorus ligand, as confirmed by detailed experimental and computational studies. This reaction mode significantly expands the pool of enantiomerically enriched functional phosphines, some of which have shown excellent efficiency for asymmetric catalysis.
The efficient and stereoselective synthesis of polysubstituted butadienes, especially the multifunctional butadienes, represents a great challenge in organic synthesis. Herein, we wish to report a ...distinctive Pd(0) carbene-initiated decarboxylative olefination approach that enables the direct coupling of diazo esters with vinylethylene carbonates (VECs), vinyl oxazolidinones, or vinyl benzoxazinones to afford alcohol-, amine-, or aniline-containing 1,3-dienes in moderate to high yields and with excellent stereoselectivity. This protocol features operational simplicity, mild reaction conditions, a broad substrate scope, and gram-scalability. Notably, a structurally unique allylic Pd(II) intermediate was isolated and characterized. DFT calculation and control experiments demonstrated that a rare Pd(0) carbene intermediate could be involved in this reaction. Moreover, the polysubstituted butadienes as novel building blocks were unprecedentedly assembled into macrocycles, which efficiently inhibited the P-glycoprotein and dramatically reversed multidrug resistance in cancer cells by 190-fold.
Heteroarenes containing carbon-silicon (C-Si) bonds are important building blocks that play an important role in the construction of natural products, pharmaceuticals, and organic materials. In this ...context, the C-H silylation of heteroarenes is a topic of intense interest. Indole C-H silylation can preferentially occur at the nucleophilic C3 and C2 position (pyrrole core), while accessing the C4-C7 positions (benzene core) of the indole remains highly challenging. Here, we show a general strategy for the regioselective C7-H silylation of indole derivatives. Mainly, the regioselectivity is determined by strong coordination of the palladium catalyst with phosphorus (III) directing group. Using this expedient synthetic strategy, the diverse C7-silylated indoles are synthesized effectively which exhibits the broad functional group compatibility. Moreover, this protocol also been extended to other heteroarenes such as carbazoles. The obtained silylated indoles have been employed in various transformations to enable the corresponding differently functionalized indole derivatives. Significantly, a cyclopalladated intermediate is successfully synthesized to test the hypothesis about the P(III)-directed C-H metalation event. A series of mechanistic experiments and density functional theory (M06-2X) calculations has shown the preferred pathway of this directed C-H silylation process.
PDF
