Developing methods for the direct functionalization of quinones for assembly of highly functionalized quinones or bioactive natural products is an essential topic in the field of direct C–H ...functionalization. Quinone units are key motifs in many bioactive compounds and materials, and many innovative methods have been elaborated for the generation of these units. A major part of the established synthetic strategies combines installation of substituents on hydroquinones, phenols, or phenyl ethers through different coupling reactions with oxidation to produce the desired quinones. Most of these above‐mentioned methods introduce multiple chemical steps; however, the synthesis of quinoid compounds through the direct C–H functionalization of simple quinones remains challenging. This minireview summarizes the recently developed achievements for assembly of functionalized quinones through direct functionalization of simple quinones. Our focus will be on the methods and mechanism of these reactions that have appeared in the last two decades.
We focus on the recent advances, mainly in the past twenty years, in the synthesis of quinoid compounds through the direct functionalization of simple quinones. These reactions are classified by reaction types, including alkylation, arylation, amination/phosphination, sulfenylation, and others, in which the scope and limits, as well as the mechanisms of these reactions, are highlighted.
An efficient cobalt(III)‐catalyzed C‐2‐selective indole C–H hydroarylation of acrolein, enones, and glyoxylates was achieved under mild reaction conditions. The versatile cobalt(III) catalyst ...displayed excellent positional selectivity with the assistance of pyrimidinyl, pyridyl, and pyrazolyl directing groups, thus overcoming the inherent C‐3 selectivity of an electrophilic indole derivatization. This approach provides an expedient route to indolyl‐substituted aldehydes, ketones, and esters with wide functional group tolerance. In addition, it also features high step‐ and atom‐economy.
A Cu0‐catalyzed protocol is proposed for the synthesis of 8‐acylquinolines through a 3+2+1 annulation starting from anthranils and phenylacetaldehydes. This protocol is of particular interest in ...preparing 8‐aldehyde quinolines, which have been hard to access so far. Both AgOTf and dioxygen played an important role in the reaction. C3‐heterocycle or phenylethylene substituted anthranils could also be employed in the reaction. An interesting esterification of aldehyde was observed.
A Cu0‐catalyzed protocol is proposed for the synthesis of 8‐acylquinolines through a 3+2+1 annulation starting from anthranils and phenylacetaldehydes. This protocol is of particular interest in preparing 8‐aldehyde quinolines, which have been hard to access so far. Both AgOTf and dioxygen played an important role in the reaction. C3‐heterocycle or phenylethylene substituted anthranils could also be employed in the reaction. An interesting esterification of aldehyde was observed.
An efficient catalytic system for Sonogashira–Hagihara‐type reactions displaying ligand acceleration in the copper‐catalyzed formation of C(sp2)C(sp) bonds is described. The structure of the ligand ...plays a key role for the coupling efficiency. Various copper sources show excellent catalytic activity, even in sub‐mol % quantities. A wide variety of substituents is tolerated in the substrates. Mechanistic details have been revealed by kinetic measurements and DFT calculations.
Just a pinch of copper! An efficient system for the formation of C(sp2)C(sp) bonds has been developed. In sub‐mol % quantities various copper sources showed excellent catalytic activity. Different combinations of aryl(hetero) iodides and terminal aryl(hetero) alkynes were applied, leading to the desired products in moderate to excellent yields (see scheme; DMEDA=N,N′‐dimethylethylenediamine). Mechanistic details of this process have been revealed by kinetic measurements and DFT calculations.
Accumulating evidence proposed Janus-associated kinase (JAK) inhibitors as therapeutic targets warranting rapid investigation.
This study evaluated the efficacy and safety of ruxolitinib, a JAK1/2 ...inhibitor, for coronavirus disease 2019.
We conducted a prospective, multicenter, single-blind, randomized controlled phase II trial involving patients with severe coronavirus disease 2019.
Forty-three patients were randomly assigned (1:1) to receive ruxolitinib plus standard-of-care treatment (22 patients) or placebo based on standard-of-care treatment (21 patients). After exclusion of 2 patients (1 ineligible, 1 consent withdrawn) from the ruxolitinib group, 20 patients in the intervention group and 21 patients in the control group were included in the study. Treatment with ruxolitinib plus standard-of-care was not associated with significantly accelerated clinical improvement in severe patients with coronavirus disease 2019, although ruxolitinib recipients had a numerically faster clinical improvement. Eighteen (90%) patients from the ruxolitinib group showed computed tomography improvement at day 14 compared with 13 (61.9%) patients from the control group (P = .0495). Three patients in the control group died of respiratory failure, with 14.3% overall mortality at day 28; no patients died in the ruxolitinib group. Ruxolitinib was well tolerated with low toxicities and no new safety signals. Levels of 7 cytokines were significantly decreased in the ruxolitinib group in comparison to the control group.
Although no statistical difference was observed, ruxolitinib recipients had a numerically faster clinical improvement. Significant chest computed tomography improvement, a faster recovery from lymphopenia, and favorable side-effect profile in the ruxolitinib group were encouraging and informative to future trials to test efficacy of ruxolitinib in a larger population.
A convenient transition metal-free procedure for the direct thiolation of 1,3,4-oxadiazole C-H bonds using diaryl disulfides has been developed. Other substrates including indole, benzothiazole, ...N-phenylbenzimidazole, and caffeine were also thiolated in this manner, providing the corresponding products in good to excellent yields.
In this study, the active noise control (ANC) method was used to suppress high-decibel and low-frequency power transformer noise. An appropriate ANC system was selected based on the transformer noise ...characteristics and experimental condition. A new filter-X least mean square (FXLMS) adaptive ANC algorithm based on offline and online secondary-path modeling was proposed to realize faster and more stable secondary-path online modeling than that of the random white-noise FXLMS algorithm and to ensure the convergence, stability, and reduction in transformer noise control. Moreover, the genetic algorithm is adopted to optimize the convergence coefficient, while the effect of the convergence coefficient on the algorithm was analyzed using simulation and theory. In addition, the transformer noise online monitoring and active control system was designed including software and hardware, and the hardware devices were selected based on the noise feature. In the 50 000 KVA transformer noise reduction experiment, the system achieved a noise reduction of 8-15 dB and an 84.10-96.86% decrease in average sound energy density in a certain area.
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•A nanoparticles-in-microparticles system was fabricated by electrospray technology for curcumin colon-targeting oral delivery in ulcerative colitis treatment.•Encapsulation in ...hydrogel microparticles could avoid the immature drug release of nanoparticles in the upper gastrointestinal tract.•Curcumin-loaded in the nanoparticles-in-microparticles systems were apt to reach colitis lesion and enter into inflammatory macrophages to suppress inflammation.
Although nano-systems can promote the cellular internalization, polymeric nanoparticles (NPs) are easily to be destroyed or eliminated in the gastrointestinal tract, which leads to premature drug release or insufficient colonic accumulation. A novel oral nano-in-micro system for the efficient colonic delivery of curcumin (Cur) was developed in this study, in which the hyaluronic acid (HA)/zein complex NPs loading Cur were embedded in alginate/chitosan hydrogel microparticles (Cur@NMPs) with the electrospray technology. The Cur@NMPs showed uniform-sized sphere with an average size of 218.36 ± 10 μm, encapsulating Cur@HA/zein NPs with the average size of 148.64 ± 3.21 nm. Cur in NMPs showed the sustained drug-release profiles in simulated gastric fluid, whereas it showed the rapid release in simulated colonic fluid. Mediated by the HA-CD44 receptor recognition, Cur@HA/zein NPs had the increased cellular uptake efficiency in macrophages. Furthermore, NMPs had the significant colon-retention and bio-adhesiveness capacity in colon tissues. As expected, the oral administration of Cur@NMPs significantly mitigated colitis symptoms in DSS-induced UC mice by inhibiting TLR4/NF-κB pathway. The above results can provide a useful drug delivery strategy for Cur in the treatment of UC by retaining the advantages of nano- and micro-scaled carriers.
During the last decades, smart tactile sensing systems based on different sensing techniques have been developed due to their high potential in industry and biomedical engineering. However, smart ...tactile sensing technologies and systems are still in their infancy, as many technological and system issues remain unresolved and require strong interdisciplinary efforts to address them. This paper provides an overview of smart tactile sensing systems, with a focus on signal processing technologies used to interpret the measured information from tactile sensors and/or sensors for other sensory modalities. The tactile sensing transduction and principles, fabrication and structures are also discussed with their merits and demerits. Finally, the challenges that tactile sensing technology needs to overcome are highlighted.
Although multitudinous nanoscale drug-delivery systems (DDSs) have been recommended to improve anti-ulcerative colitis (UC) outcomes, to enhance the mucoadhesion of nanosystems on the colon and ...specifically release the loaded drugs in response to the colon micro-environment would be critical factors. The application of curcumin (Cur), an acknowledged anti-UC phytochemical compound, for UC therapy requires more efficient nano-carriers to improve its therapeutic outcome. Herein, we developed the colon-targeted nano-micelles with mucoadhesive effect and Azo reductase-triggered drug release profiles for Cur delivery in UC treatment. Specifically, the amphiphilic block polymer containing the Azo-reductase sensitive linkage (PEG-Azo-PLGA), and catechol-modified TPGS (Cat-TPGS) were synthesized respectively. Based on the self-assembly of the mixed polymers, Cur-micelles (142.7 ± 1.7 nm of average size, 72.36% ± 1.54% of DEE) were obtained. Interestingly, the Cur-micelles exhibited the Azo-reductase sensitive particle dissociation and drug release, the enhanced cellular uptake and the prolonged retention on colonic mucosa, mediated by the strong mucoadhesion of catechol structure. Ultimately, Cur-micelles significantly mitigated colitis symptoms and accelerated colitis repair in DSS-treated mice by regulating the intestinal flora and the levels of pro-inflammatory factors (MPO, IL-6, IL-1β, and TNF-α) related to TLR4/MyD88/NF-κB signaling pathway. This work provides an effective drug delivery strategy for anti-UC drugs by oral administration.
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The oral colon-targeted mucoadhesive Cur-micelles significantly mitigated colitis symptoms and accelerated colitis repair in DSS-treated mice by regulating the intestinal flora and the levels of pro-inflammatory factors (MPO, IL-6, IL-1β, and TNF-α) related to TLR4/MyD88/NF-κB signaling pathway.
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