Unprotected C-aryl glycosides are ubiquitous in biologically active compounds and are widely used in chemical biology. The stereochemistry at the anomeric carbon of a C-glycoside often dictates its function. Despite past advances in C-glycosylation, methods that provide selective access to both α and β anomers are scarce due to the challenge of controlling stereoselectivity. Herein, we demonstrate that native sugars, when transformed into glycosyl sulfonyl hydrazide precursors, undergo efficient radical cross-coupling with (hetero)aryl halides under redox-neutral nickel catalysis. The method has broad scope and excellent functional group tolerance, enabling the stereodivergent synthesis of diverse C-(hetero)aryl glycosides in either α or β anomeric forms through ligand control.

As emerging environmental pollutants, p-phenylenediamine quinones (PPD-Qs) have widespread human exposure and documented human health toxicity, including the pregnant women. However, the enantiomer-specific transport behaviors of these chemicals across the human placental barrier have not been well elucidated. To address this gap, this study analyzed 228 paired maternal and cord serum samples for nine PPD-Qs using an enantioselective method. In maternal serum, the major PPD-Qs were N, N'-di(o-tolyl)-p-phenylenediamine quinone (PTPD-Q; mean 1.89 ng/mL, range < LOD-6.69 ng/mL) and N-phenyl-N'-cyclohexyl-p-phenylenediamine quinone (CPPD-Q; 1.72 ng/mL, < LOD-9.38 ng/mL). For cord serum, N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-Q; mean 1.70 ng/mL, range < LOD-5.69 ng/mL) and PTPD-Q (1.32 ng/mL, < LOD-6.19 ng/mL) were found at relatively higher concentrations. In maternal serum and cord serum, mean enantiomer fraction values of 6PPD-Q were 0.41 and 0.38, respectively. The highest transplacental transfer efficiency (TTE) was observed for 6PPD-Q (mean 0.98, range 0.03-4.24), followed by N, N'-di-sec-butyl-p-phenylenediamine quinone (0.91, 0.03-3.91), CPPD-Q (0.81, 0.02-4.42), and PTPD-Q (0.66, 0.02-3.46). S-6PPD-Q (mean 1.34) exhibited a higher mean TTE value than R-6PPD-Q (1.11). The physicochemical properties of PPD-Qs did not significantly correlate with their calculated TTE values. For the first time, we provide evidence of enantioselective transplacental transfer of PPD-Qs, highlighting the need for enantioselective risk assessment of these emerging contaminants during pregnancy.

The development of safe, environmentally friendly, edible antimicrobial packaging films represents a promising alternative to conventional plastic packaging for reducing spoilage and extending the shelf life of fresh food. Here, we propose a novel strategy to construct edible beta-CD-MOF/carvacrol@zein (BCCZ) composite films by intertwining beta-CD-MOF loaded with the antimicrobial essential oil carvacrol, and zein. The resulting BCCZ films exhibit high humidity-triggered, long-lasting bactericidal efficacy, effective fruit preservation, and excellent biosafety. Characterization revealed that BCCZ films possess a compact texture, hydrophilic surface, low water vapor permeability, and high humidity sensitivity. Additionally, this film act as a "storehouse" for carvacrol, enabling humidity-controlled release (96.3% release at 100% RH and only 12.0% at 43% RH on day 7). BCCZ film effectively inhibited Gram-positive Staphylococcus aureus, Gram-negative Escherichia coli, and fungi (Botrytis cinerea) through the release of liquid-phase and vapor-phase carvacrols under both direct contact and indirect contact conditions in high humidity. Owing to the film's humidity-triggered, long-term release of carvacrol, strawberries packed in BCCZ films maintained their freshness and appearance significantly better after seven days of storage at 21 degrees C. This work provides valuable insights and holds promise for the design and commercial application of safe, environmentally friendly freshness-preserving packaging films.

Starting from the pyrimidine-biphenyl compound 1 as a lead structure, a series of di-substituted pyrimidine-biphenyl compounds were designed and synthesized by introducing disubstituents to its delta-ring. All the target compounds were characterized by H-1 NMR, C-13 NMR, F-19 NMR, and HRMS. The results of herbicidal activity evaluation in the greenhouse assay showed that most of the compounds exhibited excellent herbicidal activity against Echinochloa crusgalli, Digitaria sanguinalis, and Amaranthus retroflexus in post-emergence treatments. Notably, N-(2-((4,6-dimethoxypyrimidin- 2-yl)oxy)-benzyl)-3'-methoxy-5'-methyl-[1,1'-biphenyl]-2-amine (4f) demonstrated an average pre- and post-emergence weed control of 81% against four tested weeds, exhibiting broad-spectrum herbicidal activities. The study of molecular mode of action revealed that the target compound 4f was acetohydroxyacid synthase (AHAS). 4f established extensive hydrophobic interactions with the residues within the hydrophobic cavity of AHAS, particularly enhancing the interactions with residues M352, V485, and the cofactor flavin adenine dinucleotide (FAD). Consequently, 4f (IC50=98.1 mu mol/L) exhibited higher AHAS inhibitory activity compared to the lead structure 1 (IC50=157 mu mol/L). These findings suggested that 4f was worthy of further investigation.

This study reports a novel strategy for palladium-catalyzed aryl isocyanide insertion, offering a brand-new route for the efficient synthesis of quinoline derivatives. The remarkable features of this method are reflected in two aspects. On the one hand, it ingeniously utilizes a palladium catalyst to directly and highly selectively activate the C(sp2)-H bonds of aromatic substrates, demonstrating excellent chemoselectivity. On the other hand, by integrating C(sp2)-H functionalization with [4 + 1] cyclization within a single reaction system, this approach significantly streamlines the synthesis process. It enables the direct construction of quinoline derivatives via a one-step operation starting from simple and easily accessible raw materials, achieving remarkable synthetic efficiency.

C-H functionalization has surfaced as a powerful tool in molecular synthesis. meta-Selective arene C-H activations typically rely on rather costly palladium or rhodium catalysts, elaborate template auxiliaries, or elevated temperatures, and meta-glycosylations are scarce. In contrast, we herein report on a visible-light-induced ruthenium-catalyzed meta-C-H glycosylation that utilizes a stable ruthenium-(II) catalyst under exceedingly mild conditions at room temperature. This strategy is operative without an exogenous photocatalyst. The versatile ruthenium-(II) catalyst featured high meta- and anomeric α-selectivity, employing readily accessible glycosyl bromides.

Given the prevalence of the malignant weed Chinese Sprangletop (Leptochloa chinensis (L.) Nees) in rice fields, the development of novel herbicides against this weed has aroused wide interest. Here, we report a novel diphenyl ether-pyrimidine hybrid, DEP-5, serving as a systematic pre/postemergence herbicide candidate for broad-spectrum weed control in rice fields, specifically for L. chinensis. Notably, DEP-5 exhibits over 80% herbicidal activity against the resistant biotypes even at 37.5 g a.i./ha under greenhouse conditions and has complete control of L. chinensis at 150 g a.i./ha in the rice fields. We uncover that DEP-5 acts as a noncompetitive inhibitor of acetohydroxyacid synthase (AHAS) with an inhibition constant (Ki) of 39.4 μM. We propose that DEP-5 binds to AHAS in two hydrophobic-driven binding modes that differ from commercial AHAS inhibitors. Overall, these findings demonstrate that DEP-5 has great potential to be developed into a herbicide for L. chinensis control and inspire fresh concepts for novel AHAS-inhibiting herbicide design.

Herbicides are useful tools for managing weeds and promoting food production and sustainable agriculture. In this study, we report on the development of a novel class of lipophilic pyrimidine-biphenyl (PMB) herbicides. Firstly, three PMBs, Ia, IIa, and IIIa, were rationally designed via a scaffold hopping strategy and were determined to inhibit acetohydroxyacid synthase (AHAS). Computational simulation was carried out to investigate the molecular basis for the efficiency of PMBs against AHAS. With a rational binding mode, and the highest in vitro as well as in vivo potency, Ia was identified as a preferable hit. Furthermore, these integrated analyses guided the design of eighteen new PMBs, which were synthesized via a one-step Suzuki–Miyaura cross-coupling reaction. These new PMBs, Iba-ic, were more effective in post-emergence control of grass weeds compared with Ia. Interestingly, six of the PMBs displayed 98–100% inhibition in the control of grass weeds at 750 g ai/ha. Remarkably, Ica exhibited ≥ 80% control against grass weeds at 187.5 g ai/ha. Overall, our comprehensive and systematic investigation revealed that a structurally distinct class of lipophilic PMB herbicides, which pair excellent herbicidal activities with new interactions with AHAS, represent a noteworthy development in the pursuit of sustainable weed control solutions.

4-Quinolone derivatives undergo an unexpected ring expansion reaction with alpha-halo esters/phosphonates/sulfones in the presence of a base, such as NaH, to produce novel benzazepinones. Under these mild and transition-metal-free conditions, most substrates gave moderate to excellent yields. The reaction could be applied in gram-scale synthesis of drug-like molecules that greatly accelerated our structure-activity relationship studies. A plausible mechanism was proposed.

Glycosyl donor activation emerged as an enabling technology for anomeric functionalization, but aimed primarily at O-glycosylation. In contrast, we herein disclose mechanistically distinct electrochemical glycosyl bromide donor activations via halogen-atom transfer and anomeric C-glycosylation. The anomeric radical addition to alkenes led to C-alkyl glycoside synthesis under precious metal-free reaction conditions from readily available glycosyl bromides. The robustness of our e-XAT strategy was further mirrored by C-aryl and C-acyl glycosides assembly through nickela-electrocatalysis. Our approach provides an orthogonal strategy for glycosyl donor activation with expedient scope, hence representing a general method for direct C-glycosides assembly.

Radikalische Glykosyladditionsreaktionen sind gut erforscht und haben sich als eine effiziente Syntheseroute von C ‐Alkylglykosiden erwiesen. Jedoch sind mehrkomponentige Domino‐Transformationen, für einen schnellen und kontrollierbaren Aufbau strukturell diversifizierter C ‐Alkylglykoside, in einem einzigen Schritt, noch selten. Im Gegensatz dazu berichten wir hier über eine Ruthenium(II)‐katalysierte Domino‐ meta ‐C−H‐Ethylglykosylierung, welche die Herstellung anspruchsvoller meta ‐ C ‐Alkylglykoside ermöglicht. Unsere Ruthenium(II)‐Katalyse zeichnete sich durch milde Reaktionsbedingungen, ausschließlicher meta ‐Selektivität und einer hohen anomeren Selektivität aus. Darüber hinaus ermöglichte die Ruthenium(II)‐katalysierte Domino‐ meta ‐C−H‐Glykosylierung die Synthese vielseitiger 1,2‐ trans ‐ C ‐Alkylglykoside mit kommerziell erhältlichen Vinylarenen, Acrylaten und leicht zugänglichen Glykosylbromiden.

Glycosyl anomeric radical addition reactions have been well-explored and proved efficient for the C-alkyl glycosides synthesis, but multicomponent Domino transformations for the rapid and controllable construction of structurally diversified C-alkyl glycosides in a single step are still rare. In contrast, we, herein, report a ruthenium(II)-catalyzed Domino meta-C-H ethyl glycosylation, enabling the construction of challenging meta-C-alkyl glycosides. Our ruthenium(II) catalysis was reflected by the mild reaction condition, exclusive meta-site selectivity and high levels of anomeric selectivity. In addition, the ruthenium(II)-catalyzed Domino meta-C-H glycosylation allowed for the synthesis of versatile 1,2-trans-C-alkyl glycosides with commercially available vinyl arenes, acrylates and easily accessible glycosyl bromides.

Ruthenium-catalyzed σ-bond activation-assisted meta-C-H functionalization has emerged as a useful tool to forge distal C-C bonds. However, given the limited number of mechanistic studies, a clear understanding of the origin of the site-selectivity and the complete reaction pattern is not available. Here, we present systematic computational studies on ruthenium-catalyzed C-H functionalization with primary, secondary, tertiary alkyl bromides and aryl bromides. The C-H scission and the C-C formation were carefully examined. Monocyclometalated ruthenium(II) complexes were identified as the active species, which then underwent inner-sphere single electron transfer (ISET) to activate the organic bromides. The site-selectivity results from the competition between the close-shell reductive elimination and the open-shell radical coupling. Based on this mechanistic understanding, a multilinear regression model was built to predict the site-selectivity, which was further validated by experiments.

AbstractC‐Oligosaccharide sind pharmakologisch relevant, weil sie hydrolysebeständiger sind als O‐Oligosaccharide. Trotz unbestreitbarer Fortschritte sind C‐Oligosaccharide nach wie vor wenig erforscht, meist aufgrund des Mangels an effizienten und selektiven Strategien für den Aufbau von C‐C‐Bindungen. Im Gegensatz dazu veröffentlichen wir hier eine vielseitige und robuste Strategie für die Synthese strukturell komplexer C‐Oligosaccharide via einer katalytischen C(sp3)‐H‐Aktivierung. Auf diese Weise ist eine Fülle von komplexen interglykosidischen (2→1)‐ und (1→1)‐C‐Oligosaccharide mittels einer Palladium‐katalysierter C(sp3)‐H‐Glykosid‐Glykosylierung einfacher zugänglich. Die Isolierung von Schlüsselintermediaten des Palladacyclus und experimentell isotopisch markierten Verbindungen ergaben eine trans‐ Stereoselektivität für die C(sp3)‐H‐Glykosylierung. Der glykosidische C(sp3)‐H‐Aktivierungsmechanismus wurde ebenfalls für die Diversifizierung von Furanosen, Pyranosen und Disacchariden angewandt.

Catalyzed C-H activation has surfaced as an enabling tool for molecular assembly, with a plethora of translational applications. The enormous developments toward the utilization of ubiquitous C-H bonds as latent functionalities has thus enabled the efficient assembly of increasingly complex scaffolds. Recently, a paradigm shift has occurred to enable sustainable, industry-relevant C-H functionalization manifolds. Among the most prominent transition metals for C-H activations, ruthenium offers several salient features, including cost-effective, robust, and mild C-H activations with unique reactivities for remote functionalization. Indeed, ruthenium(II) catalysis by carboxylate assistance offers a highly functional group tolerant and predictable toolbox for directed as well as nondirected C-H functionalizations, with a major impact to improve the sustainability in industrial settings. These assets have allowed the use of nontoxic, nonflammable, and cost-effective H2O as a reaction medium for sustainable ruthenium(II)-catalyzed C-H activations. In this perspective, we summarize the potential of water for sustainable ruthenium(II)-catalyzed C-H activations up to February 2022.

Fungal infections caused by Candida species are among the most prevalent in hospitalized patients. However, current methods for the detection of Candida fungal cells in clinical samples rely on time-consuming assays that hamper rapid and reliable diagnosis. Herein, we describe the rational development of new Phe-BODIPY amino acids as small fluorogenic building blocks and their application to generate fluorescent antimicrobial peptides for rapid labelling of Candida cells in urine. We have used computational methods to analyse the fluorogenic behaviour of BODIPY-substituted aromatic amino acids and performed bioactivity and confocal microscopy experiments in different strains to confirm the utility and versatility of peptides incorporating Phe-BODIPYs. Finally, we have designed a simple and sensitive fluorescence-based assay for the detection of Candida albicans in human urine samples.

为解决传统加热法合成异喹啉-离子液体存在的问题,开发了一种超声辅助合成异喹啉-离子液体的方法.通过异喹啉季铵化过程的对比研究,证明了该方法具有环保性强、产率高、反应时间短等优点.将其扩展至阴离子交换反应,发现超声辐射法有效促进了异喹啉溴化物与简单阴离子[N(CF3SO2)2]?和[PF6]?,以及与复杂阴离子2,4-二氯苯氧乙酸的阴离子交换反应.对所得到的异喹啉-离子液体进行了结构表征以及热行为和溶解度的研究和讨论.结果表明,所得液体具有良好的热稳定性,为快速、高效建立绿色多功能化离子液体库奠定了基础.

C-oligosaccharides are pharmacologically relevant because they are more hydrolysis-resistant than O-oligosaccharides. Despite indisputable advances, C-oligosaccharides continue to be underdeveloped, likely due to a lack of efficient and selective strategies for the assembly of the interglycosidic C-C linkages. In contrast, we, herein, report a versatile and robust strategy for the synthesis of structurally complex C-oligosaccharides via catalyzed C(sp3 )-H activations. Thus, a wealth of complex interglycosidic (2→1)- and (1→1)-C-oligosaccharides becomes readily available by palladium-catalyzed C(sp3 )-H glycoside glycosylation. The isolation of key palladacycle intermediates and experiments with isotopically-labeled compounds identified a trans-stereoselectivity for the C(sp3 )-H glycosylation. The glycoside C(sp3 )-H activation manifold was likewise exploited for the diversification of furanoses, pyranoses and disaccharides.