Copper/O2-Mediated Oxidative C-C Activation of Nitriles for Selective Acylation-Bromination of Anilines.

This study reports selective dual amino acylation and C-H bromination of aniline compounds enabled by Cu/O2 catalyst systems. This method involves crucial oxidation-induced C-CN bond cleavage of α-methylene nitriles to generate an acylcyanide intermediate that is facilely intercepted by anilines. After amino acylation, the Cu(II) precatalyst in combination with NBS generates Cu(III)-Br in situ that engages in selective electrophilic para- or ortho-C-H bromination. The substrate scope, mechanistic aspects, and late-stage functionalization of biologically active anilines are studied. This study shows the synthetic potential of oxidative C-CN bond activation of nitriles for the development of valuable reactions.

Significance of atherosclerotic plaque location in recanalizing non-acute long-segment occlusion of the internal carotid artery.

To investigate the significance of atherosclerotic plaque location in hybrid surgery comprising both endovascular recanalization approaches and carotid endarterectomy for symptomatic atherosclerotic non-acute long-segment occlusion of the internal carotid artery (ICA), 162 patients were enrolled, including 120 (74.1%) patients in the proximal plaque group and 42 (25.9%) in the distal plaque group. Surgical recanalization was performed in all patients, with successful recanalization in 119 (99.2%) patients in the proximal and 39 (92.9%) in the distal plaque group. The total successful recanalization rate was 97.5% (158/162) with a failure rate of 2.5% (4/162). Periprocedural complications occurred in 5 (4.2% or 5/120) patients in the proximal plaque group, including neck infection in two (1.7%), recurrent nerve injury in 1 (0.8%), and laryngeal edema in 2 (1.7%), and 2 (4.8%) in the distal plaque group, including femoral puncture infection in 2 (4.8%). No severe complications occurred in either group. Univariate analysis showed plaque location was a significant (P = 0.018) risk factor for successful recanalization, and multivariate analysis indicated that the plaque location remained a significant independent risk factor for recanalization success (P = 0.017). In follow-up 6-48 months after the recanalization surgery, reocclusion occurred in two (2.8%) patients in the proximal plaque group and 4 (13.3%) in the distal plaque group. In conclusion, although hybrid surgery achieves similar outcomes in patients with ICA occlusion caused by either proximal or distal atherosclerotic plaques, plaque location may be a significant risk factor for successful recanalization of symptomatic non-acute long-segment ICA occlusion.

Changes in soil aggregate stability and aggregate-associated carbon under different slope positions in a karst region of Southwest China.

Soil aggregates are crucial for reducing soil erosion and enhancing soil organic carbon sequestration. However, knowledge regarding influences of different slope positions on compositions and carbon content for different soil aggregates is limited. Soil samples were collected from various slope positions including dip slope, anti-dip slope and valley depression in the Longtan karst valley of Southwest China. Contents of macroaggregate (> 0.25 mm), microaggregate (0.053-0.25 mm) and silt and clay fraction (< 0.053 mm), and aggregate-associated carbon contents under the three slope positions were measured. Compared to the anti-dip slope, the mean weight diameter under the dip slope and valley depression decreased by 28.48 % and 58.79 %, respectively, while the geometric mean diameter decreased by 39.01 % and 62.57 %, respectively. The mean carbon content in silt and clay fraction was 27.59 % and 21.00 % lower than the macroaggregate- and microaggregate-associated carbon content, respectively. Under the valley depression and dip slope, soil organic carbon contents in bulk soil (37.67 % and 10.36 %, respectively), microaggregate (37.56 % and 4.95 %), and silt and clay fraction (39.99 % and 12.84 %, respectively) were significantly lower than those under the anti-dip slope. However, the difference in macroaggregate-associated carbon content among the three slope positions was not significant. The silt and clay fraction was the major contributor to soil carbon pool in bulk soil in the study area because of its high content. Compared to the anti-dip slope, contribution of macroaggregates to soil carbon pool under the dip slope and valley depression decreased by 25.53 % and 47.95 %, respectively, whereas the contribution of silt and clay fraction increased by 22.68 % and 42.66 %, respectively. These results suggested that the anti-dip slope surpassed both the dip slope and valley depression in carbon sequestration and soil and water conservation in karst regions.

Ruthenium-Catalyzed Difunctionalization of Vinyl Cyclopropanes for Double m-C(sp2)-H/C-5(sp3)-H Functionalization.

With in-depth research on 1,2-difunctionalization, remote difunctionalization has garnered widespread attention for achieving multifunctionality. Herein, we report a strategy for achieving remote difunctionalization under mild conditions. This strategy exhibited good substrate suitability and functional group tolerance. In addition, the significance of this method is further evidenced by its successful application in scaling up and conducting additional transformations of target compounds. Mechanistic studies showed that a radical might be involved in this process.

A Practical and Regioselective Strategy for Aromatic C-H Difunctionalization via Site-Selective C-H Thianthrenation.

Herein, we present a novel Catellani-type reaction that employed aryl-thianthrenium salts as aryl substrates to trigger the subsequent palladium/norbornene cooperatively catalyzed progress. This strategy can achieve site-selective C-H difunctionalization of aryl compounds without directing groups or a known initiating reagent. A series of functionalized syntheses of bioactive molecules further demonstrated the potential of this strategy.

Visible-Light-Mediated Synthesis of C-Alkyl Glycosides via Glycosyl Radical Addition and Aryl Migration.

A visible-light-induced glycoarylation of activated olefins has been accomplished. Glycosyl radicals are generated via radical transfer strategies between (TMS)3SiOH and glycosyl bromides. Subsequent radical translocation and rapid 1,4-aryl migration form ß-sugar amide derivatives, and eight types of sugars are compatible with this reaction. Further, the cascade reaction produced a quaternary carbon center with good functional group adaptability and high regioselectivity in mild conditions.

Stereoselective Synthesis of Multisubstituted Alkenes via Ruthenium-Catalyzed Remote Migration Arylation of Nonactivated Olefins.

Polysubstituted alkenes are an important class of organic intermediates that widely exist in various natural products and drug molecules. Herein, we reported a stereoselective synthesis of multisubstituted alkenes via ruthenium-catalyzed remote migration arylation of nonactivated olefins. This strategy exhibited wide substrate suitability and excellent functional group tolerance. In addition, we demonstrated the indispensable role of two types of ruthenium through mechanism experiments.

Photoredox-Catalyzed N-Directed Regioselective Difluoroalkylation of Unactivated C(sp3)-H Bonds.

We report a redox-neutral, visible-light-mediated difluoroalkylation of unactivated C(sp3)-H bonds in amides via nitrogen-centered radicals triggered intramolecular hydrogen atom transfer. Notably, all types (tertiary, secondary, and primary) of γ-C(sp3)-H bonds displayed excellent reactivity. This methodology presents a facile route for the regioselective introduction of α,α-difluoroketone fragments into organic molecules. Moreover, the resulting gem-difluoroketones can be readily converted to structurally diverse difluoro-containing molecules, offering broad potential applications in medicinal chemistry and chemical biology.

A functional gene module identification algorithm in gene expression data based on genetic algorithm and gene ontology.

Since genes do not function individually, the gene module is considered an important tool for interpreting gene expression profiles. In order to consider both functional similarity and expression similarity in module identification, GMIGAGO, a functional Gene Module Identification algorithm based on Genetic Algorithm and Gene Ontology, was proposed in this work. GMIGAGO is an overlapping gene module identification algorithm, which mainly includes two stages: In the first stage (initial identification of gene modules), Improved Partitioning Around Medoids Based on Genetic Algorithm (PAM-GA) is used for the initial clustering on gene expression profiling, and traditional gene co-expression modules can be obtained. Only similarity of expression levels is considered at this stage. In the second stage (optimization of functional similarity within gene modules), Genetic Algorithm for Functional Similarity Optimization (FSO-GA) is used to optimize gene modules based on gene ontology, and functional similarity within gene modules can be improved. Without loss of generality, we compared GMIGAGO with state-of-the-art gene module identification methods on six gene expression datasets, and GMIGAGO identified the gene modules with the highest functional similarity (much higher than state-of-the-art algorithms). GMIGAGO was applied in BRCA, THCA, HNSC, COVID-19, Stem, and Radiation datasets, and it identified some interesting modules which performed important biological functions. The hub genes in these modules could be used as potential targets for diseases or radiation protection. In summary, GMIGAGO has excellent performance in mining molecular mechanisms, and it can also identify potential biomarkers for individual precision therapy.

Water deficit aggravated the inhibition of photosynthetic performance of maize under mercury stress but is alleviated by brassinosteroids.

Mercury (Hg) significantly inhibits maize (Zea mays L.) production, which could be aggravated by water deficit (WD) due to climate change. However, there is no report on the maize in response to combined their stresses. This work was conducted for assessing the response and adaptive mechanism of maize to combined Hg and WD stress using two maize cultivars, Xianyu (XY) 335 and Yudan (YD) 132. The analysis was based on plant growth, physiological function, and transcriptomic data. Compared with the single Hg stress, Hg accumulation in whole plant and translocation factor (TF) under Hg+WD were increased by 64.51 % (1.44 mg kg-1) and 260.00 %, respectively, for XY 335; and 50.32 % (0.62 mg kg-1) and 220.02 %, respectively, for YD 132. Combined Hg and WD stress further increased the reactive oxygen species accumulation, aggravated the damage of the thylakoid membrane, and decreased chlorophyll content compared with single stress. For example, Chl a and Chl b contents of XY 335 were significantly decreased by 48.67 % and 28.08 %, respectively at 48 h after Hg+WD treatment compared with Hg stress. Furthermore, transcriptome analysis revealed that most of down-regulated genes were enriched in photosynthetic-antenna proteins, photosynthesis, chlorophyll and porphyrin metabolism pathways (PsbS1, PSBQ1 and FDX1 etc.) under combined stress, reducing light energy capture and electron transport. However, most genes related to the brassinosteroids (BRs) signaling pathway were up-regulated under Hg+WD stress. Correspondingly, exogenous BRs significantly enhanced the maize tolerance to stress by decreasing Hg accumulation and TF, and raising activities of antioxidant enzyme, the content of chlorophyll and photosynthetic performance. The PI, Fv/Fm and Fv/Fo of Hg+WD+BR treatment were increased by 29.88 %, 32.06 %, and 14.56 %, respectively, for XY 335 compared to Hg+WD. Overall, combined Hg and WD stress decreased photosynthetic efficiency by adversely affecting light absorption and electron transport, especially in stress-sensitive variety, but BRs could alleviate the inhibition of photosynthesis, providing a novel strategy for enhancing crop Hg and WD tolerance and food safety.

Copper-Catalyzed Hydrogen Atom Transfer and Aryl Migration Strategy for the Arylalkylation of Activated Alkenes.

Herein, we describe the copper-catalyzed arylalkylation of activated alkenes via hydrogen-atom transfer and aryl migration strategy. The reaction was carried out through a radical-mediated continuous migration pathway using N-fluorosulfonamides as the alkyl source. The primary, secondary, and tertiary alkyl radicals formed by intramolecular hydrogen-atom transfer proceeded smoothly. This methodology is an efficient approach for the synthesis of various amide derivatives possessing a quaternary carbon center with good yields and high regioselectivity.

Site-selective coupling of remote C(sp3)-H/meta-C(sp2)-H bonds enabled by Ru/photoredox dual catalysis and mechanistic studies.

Construction of C(sp2)-C(sp3) bonds via regioselective coupling of C(sp2)-H/C(sp3)-H bonds is challenging due to the low reactivity and regioselectivity of C-H bonds. Here, a novel photoinduced Ru/photocatalyst-cocatalyzed regioselective cross-dehydrogenative coupling of dual remote C-H bonds, including inert γ-C(sp3)-H bonds in amides and meta-C(sp2)-H bonds in arenes, to construct meta-alkylated arenes has been accomplished. This metallaphotoredox-enabled site-selective coupling between remote inert C(sp3)-H bonds and meta-C(sp2)-H bonds is characterized by its unique site-selectivity, redox-neutral conditions, broad substrate scope and wide use of late-stage functionalization of bioactive molecules. Moreover, this reaction represents a novel case of regioselective cross-dehydrogenative coupling of unactivated alkanes and arenes via a new catalytic process and provides a new strategy for meta-functionalized arenes under mild reaction conditions. Density functional theory (DFT) calculations and control experiments explained the site-selectivity and the detailed mechanism of this reaction.

Ruthenium-Catalyzed Stereo- and Site-Selective ortho- and meta-C-H Glycosylation and Mechanistic Studies.

C-aryl glycosides are popular basic skeletons in biochemistry and pharmaceutical chemistry. Herein, ruthenium-catalyzed highly stereo- and site-selective ortho- and meta-CAr -H glycosylation is described. A series of C-aryl pyranosides and furanosides were synthesized by this method. The strategy showed good substrate scope, and various N-heterocyclic directing groups were compatible with the reaction system. A mechanistic study suggested that the key pathway of ortho-CAr -H glycosylation might involve oxidative addition/reduction elimination, whereas aryl meta-C-H glycosylation was mediated by σ-activation. Density functional theory calculations also showed that the high stereoselectivity of meta-CAr -H glycosylation was due to steric hindrance.

Mercury stress tolerance in wheat and maize is achieved by lignin accumulation controlled by nitric oxide.

Nitric oxide (NO) is an important phytohormone for plant adaptation to mercury (Hg) stress. The effect of Hg on lignin synthesis, NO production in leaf, sheath and root and their relationship were investigated in two members of the grass family - wheat and maize. Hg stress decreased growth and lignin contents, significantly affected phenylpropanoid and monolignol pathways (PAL, phenylalanine ammonia-lyase; 4-coumarate: CoA ligase, 4CL; cinnamyl alcohol dehydrogenase, CAD), with maize identified to be more sensitive to Hg stress than wheat. Among the tissue types, sheath encountered severe damage compared to leaves and roots. Hg translocation in maize was about twice that in wheat. Interestingly, total NO produced under Hg stress was significantly decreased compared to control, with maximum reduction of 43.4% and 42.9% in wheat and maize sheath, respectively. Regression analysis between lignin and NO contents or the activities of three enzymes including CAD, 4CL and PAL displayed the importance of NO contents, CAD, 4CL and PAL for lignin synthesis. Further, the gene expression profiles encoding CAD, 4CL and PAL provided support for the damaging effect of Hg on wheat sheath, and maize shoot. To validate NO potential to mitigate Hg toxicity in maize and wheat, NO donor and NO synthase inhibitor were supplemented along with Hg. The resulting phenotype, histochemical analysis and lignin contents showed that NO mitigated Hg toxicity by improving growth and lignin synthesis and accumulation. In summary, Hg sensitivity was higher in maize seedlings compared to wheat, which was associated with the lower lignin contents and reduced NO contents. External supplementation of NO is proposed as a sustainable approach to mitigate Hg toxicity in maize and wheat.

One-Pot Stereoselective Synthesis of 2,3-Diglycosylindoles and Tryptophan-C-glycosides via Palladium-Catalyzed C-H Glycosylation of Indole and Tryptophan.

We described a novel palladium-catalyzed C-H glycosylation of indole or tryptophan for a one-pot stereoselective synthesis of 2,3-diglycosylindoles and tryptophan-C-glycosides. In this strategy, the use of air and base-free and ligand-free conditions provided a highly efficient route to construct C-glycosides. The method can be applied to a wide range of cost-effective and convenient glycosyl chloride donors. Mechanistic studies indicated that the indole 2,3-diglycosylation sequence was C3 and then C2.

Palladium-catalyzed rearrangement reaction to access 1-phenanthrol derivatives.

This manuscript describes an unusual Pd-catalyzed rearrangement reaction. It provides efficient access to 1-phenanthrol derivatives using allyloxy-tethered aryl iodides. This rearrangement process involves the cleavage of a C-I bond, a C-O bond and C-H bonds, and the formation of two C-C bonds in one-pot. It is likely that the key to the success of this rearrangement is via ß-carbon elimination from a strained palladacycle.

Three-Component Ruthenium-Catalyzed meta-C-H Alkylation of Phenol Derivatives.

Herein, we realized the multicomponent reactions of phenol derivatives via a six-membered cycloruthenated intermediate for the first time. This strategy exhibited good substrate suitability and functional group tolerance with various phenol derivatives and provided a potential synthetic drug approach. Mechanistic studies showed that a radical might be involved in this process. In addition, the meta alkylated phenol was obtained by further removal of the directing group.

Highly regioselective and stereoselective synthesis of C-Aryl glycosides via nickel-catalyzed ortho-C-H glycosylation of 8-aminoquinoline benzamides.

C-Aryl glycosides are of high value as drug candidates. Here a novel and cost-effective nickel catalyzed ortho-CAr-H glycosylation reaction with high regioselectivity and excellent α-selectivity is described. This method shows great functional group compatibility with various glycosides, showing its synthetic potential. Mechanistic studies indicate that C-H activation could be the rate-determining step.

Modular Synthesis of Aryl Thio/Selenoglycosides via the Catellani Strategy.

We described a novel palladium-catalyzed domino procedure for the preparation of (hetero)aryl thio/selenoglycosides. Readily available (hetero)aryl iodides and easily accessible 1-thiosugars/1-selenosugars are utilized as the substrates. Meanwhile, 10 types of sugars are quite compatible with this reaction with good regio- and stereoselectivity, high efficiency, and broad applicability (up to 89%, 53 examples). This method enables the straightforward formation of the C(sp2)-S/Se bond of (hetero)aryl thio/selenoglycosides.