High stocking rates effects in continuous season long grazing reduces the contribution of microbial necromass to soil organic carbon in a semi-arid grassland in Inner Mongolia.

Livestock grazing strongly influences the accumulation of soil organic carbon (SOC) in grasslands. However, whether the changes occurring in SOC content under different intensities of continuous summer long grazing are associated with the changes in microbially-derived necromass C remains unclear. Here, we established a sheep grazing experiment in northern China in 2004 with four different stocking rates. Soil samples were collected after 17 years of grazing and analyzed for physical, chemical, and microbial characteristics. Grazing decreased SOC and microbial necromass carbon (MNC). Notably, grazing also diminished contributions of MNC to SOC. MNC declined with decreasing plant carbon inputs with degradation of the soil environment. Direct reductions in microbial necromass C, which indirectly reduced SOC, resulted from reduced in plant C inputs and microbial abundance and diversity. Our study highlights the key role of stocking rate in governing microbial necromass C and SOC and the complex relationships these variables.

Effects of inhaled fine particulate matter on the lung injury as well as gut microbiota in broilers.

Fine particulate matter (PM2.5) has been widely regarded as an important environmental risk factor that has widely influenced health of both animals and humans. Lung injury is the main cause of PM2.5 affecting respiratory tract health. Gut microbiota participates in the development of lung injury in many pathological processes. However, there is still unknown the specific effects of PM2.5 on the gut-lung axis in broilers. Thus, we conducted a broiler model based on 3-wk-old male Arbor Acres broiler to explore the underlying mechanism. Our results showed that PM2.5 exposure triggered TLR4 signaling pathway and induced the increase of IL-6, IFN-γ, TNF-α expression as well as the decrease of IL-10 expression in the lung. Inhaled PM2.5 exposure significantly altered the gut microbiota diversity and community. Specifically, PM2.5 exposure decreased α diversity and altered ß diversity of gut microbiota, and reduced the abundance of DTU089, Oscillospirales, Staphylococcus, and increased the Escherichia-Shigella abundance, leading to the increase of gut-derived lipopolysaccharides (LPS). Moreover, PM2.5 significantly disrupted the intestinal epithelial barrier by reducing the expression of muc2 and claudin-1 to increase intestinal permeability, which possibly facilitated the LPS translocation into the blood. Spearman analysis revealed that gut microbiota dysbiosis was positively related to TLR4, TNF-α, and IFN-γ expression in the lung. In summary, our results showed that PM2.5 exposure induced lung injury by causing inflammation and triggering TLR4 signaling pathway, and also induced gut microbiota dysbiosis resulting in the overproduction of gut-derived LPS. And gut microbiota dysbiosis may be associated with lung injury. The above results provide basis data to comprehend the potential role of gut microbiota dysbiosis in the lung injury as well as providing a new regulatory target for alleviating lung injury associated with environmental pollutants.

Comparative transcriptomics reveal differential gene expression among Plasmodium vivax geographical isolates and implications on erythrocyte invasion mechanisms.

The documentation of Plasmodium vivax malaria across Africa especially in regions where Duffy negatives are dominant suggests possibly alternative erythrocyte invasion mechanisms. While the transcriptomes of the Southeast Asian and South American P. vivax are well documented, the gene expression profile of P. vivax in Africa is unclear. In this study, we examined the expression of 4,404 gene transcripts belong to 12 functional groups and 43 erythrocyte binding gene candidates in Ethiopian isolates and compared them with the Cambodian and Brazilian P. vivax transcriptomes. Overall, there were 10-26% differences in the gene expression profile amongst geographical isolates, with the Ethiopian and Cambodian P. vivax being most similar. Majority of the gene transcripts involved in protein transportation, housekeeping, and host interaction were highly transcribed in the Ethiopian isolates. Members of the reticulocyte binding protein PvRBP2a and PvRBP3 expressed six-fold higher than Duffy binding protein PvDBP1 and 60-fold higher than PvEBP/DBP2 in the Ethiopian isolates. Other genes including PvMSP3.8, PvMSP3.9, PvTRAG2, PvTRAG14, and PvTRAG22 also showed relatively high expression. Differential expression patterns were observed among geographical isolates, e.g., PvDBP1 and PvEBP/DBP2 were highly expressed in the Cambodian but not the Brazilian and Ethiopian isolates, whereas PvRBP2a and PvRBP2b showed higher expression in the Ethiopian and Cambodian than the Brazilian isolates. Compared to Pvs25, gametocyte genes including PvAP2-G, PvGAP (female gametocytes), and Pvs47 (male gametocytes) were highly expressed across geographical samples.

Health Information on Pre-Exposure Prophylaxis From Search Engines and Twitter: Readability Analysis.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is proven to prevent HIV infection. However, PrEP uptake to date has been limited and inequitable. Analyzing the readability of existing PrEP-related information is important to understand the potential impact of available PrEP information on PrEP uptake and identify opportunities to improve PrEP-related education and communication. OBJECTIVE: We examined the readability of web-based PrEP information identified using search engines and on Twitter. We investigated the readability of web-based PrEP documents, stratified by how the PrEP document was obtained on the web, information source, document format and communication method, PrEP modality, and intended audience. METHODS: Web-based PrEP information in English was systematically identified using search engines and the Twitter API. We manually verified and categorized results and described the method used to obtain information, information source, document format and communication method, PrEP modality, and intended audience. Documents were converted to plain text for the analysis and readability of the collected documents was assessed using 4 readability indices. We conducted pairwise comparisons of readability based on how the PrEP document was obtained on the web, information source, document format, communication method, PrEP modality, and intended audience, then adjusted for multiple comparisons. RESULTS: A total of 463 documents were identified. Overall, the readability of web-based PrEP information was at a higher level (10.2-grade reading level) than what is recommended for health information provided to the general public (ninth-grade reading level, as suggested by the Department of Health and Human Services). Brochures (n=33, 7% of all identified resources) were the only type of PrEP materials that achieved the target of ninth-grade reading level. CONCLUSIONS: Web-based PrEP information is often written at a complex level for potential and current PrEP users to understand. This may hinder PrEP uptake for some people who would benefit from it. The readability of PrEP-related information found on the web should be improved to align more closely with health communication guidelines for reading level to improve access to this important health information, facilitate informed decisions by those with a need for PrEP, and realize national prevention goals for PrEP uptake and reducing new HIV infections in the United States.

Fine Particulate Matter Perturbs the Pulmonary Microbiota in Broiler Chickens.

(1) Fine particulate matter (PM2.5) seriously affects the respiratory tract health of both animals and humans. Growing evidence indicates that the pulmonary microbiota is involved in the development of respiratory tract health; however, there is still much that is unknown about the specific changes of pulmonary microbiota caused by PM2.5 in broilers. (2) In this experiment, a total of 48 broilers were randomly divided into a control group and PM-exposure group. The experiment lasted for 21 days. Microbiota, inflammation biomarkers, and histological markers in the lungs were determined. (3) On the last day of the experiment, PM significantly disrupted the structure of lung tissue and induced chronic pulmonary inflammation by increasing IL-6, TNFα, and IFNγ expression and decreasing IL-10 expression. PM exposure significantly altered the α and ß diversity of pulmonary microbiota. At the phylum level, PM exposure significantly decreased the Firmicutes abundance and increased the abundance of Actinobacteria and Proteobacteria. At the genus level, PM exposure significantly increased the abundance of Rhodococcus, Achromobacter, Pseudomonas, and Ochrobactrum. We also observed positive associations of the above altered genera with lung TNFα and IFNγ expression. (4) The results suggest that PM perturbs the pulmonary microbiota and induces chronic inflammation, and the pulmonary microbiota possibly contributes to the development of lung inflammation.

Analysis of the Differential Expression and Antiviral Activity of Porcine Interferon-α In Vitro.

Porcine interferon α (poIFN-α) is a crucial cytokine that can prevent and treat viral infections. Seventeen functional porcine IFN-α subtypes were found in the porcine genome. In this study, multiple sequence alignment was performed to analyze IFN-α protein structure and function. Phylogenetic tree analysis of the poIFN gene family defined the evolutionary relationship of various subtypes. PoIFN-αs, including poIFN-α1-17, were expressed in an Escherichia coli expression system. The antiviral activities of these IFN-α proteins against vesicular stomatitis virus (VSV) and pseudorabies virus (PRV) were examined in PK-15 cells. We found that the antiviral activity of different poIFN-α molecules greatly differed as follows: the poIFN-α14 and 17 subtypes had the greatest antiviral activities against VSV and PRV in PK-15 cells, poIFN-α1, 2, 3, and 8 exhibited lower biological activities, and poIFN-α4, 5, 6, 7, 9, 10, 11, 12, 13, and 16 had minimal or no effect in the tested target cell‒virus systems. Moreover, our studies demonstrated that the antiviral activity of IFN-α was positively correlated with the induction of IFN-stimulated genes, such as 2'-5' oligoadenylate synthetase 1 (OSA1), interferon-stimulated gene 15 (ISG15), myxoma resistance protein 1 (Mx1), and protein kinase R (PKR). Thus, our experimental results provide important information about the antiviral functions and mechanism of poIFN-α.

Comparative transcriptomics reveal differential gene expression in Plasmodium vivax geographical isolates and implications on erythrocyte invasion mechanisms.

Plasmodium vivax uses Duffy binding protein (PvDBP1) to bind to the Duffy Antigen-Chemokine Receptor (DARC) to invade human erythrocytes. Individuals who lack DARC expression (Duffy-negative) are thought to be resistance to P. vivax. In recent years, P. vivax malaria is becoming more prevalent in Africa with a portion of these cases detected in Duffy-negatives. Apart from DBP1, members of the reticulocyte binding protein (RBP) and tryptophan-rich antigen (TRAg) families may also play a role in erythrocyte invasion. While the transcriptomes of the Southeast Asian and South American P. vivax are well documented, the gene expression profile of P. vivax in Africa and more specifically the expression level of several erythrocyte binding gene candidates as compared to DBP1 are largely unknown. This paper characterized the first P. vivax transcriptome in Africa and compared with those from the Southeast Asian and South American isolates. The expression of 4,404 gene transcripts belong to 12 functional groups including 43 specific erythrocyte binding gene candidates were examined. Overall, there were 10-26% differences in the gene expression profile amongst the geographical isolates, with the Ethiopian and Cambodian P. vivax being most similar. Majority of the gene transcripts involved in protein transportation, housekeeping, and host interaction were highly transcribed in the Ethiopian P. vivax. Erythrocyte binding genes including PvRBP2a and PvRBP3 expressed six-fold higher than PvDBP1and 60-fold higher than PvEBP/DBP2. Other genes including PvRBP1a, PvMSP3.8, PvMSP3.9, PvTRAG2, PvTRAG14, and PvTRAG22 also showed relatively high expression. Differential expression was observed among geographical isolates, e.g., PvDBP1 and PvEBP/DBP2 were highly expressed in the Cambodian but not the Brazilian and Ethiopian isolates, whereas PvRBP2a and PvRBP2b showed higher expression in the Ethiopian and Cambodian than the Brazilian isolates. Compared to Pvs25, the standard biomarker for detecting female gametocytes, PvAP2-G (PVP01_1440800), GAP (PVP01_1403000), and Pvs47 (PVP01_1208000) were highly expressed across geographical samples. These findings provide an important baseline for future comparisons of P. vivax transcriptomes from Duffy-negative infections and highlight potential biomarkers for improved gametocyte detection.

Biodiversity and soil pH regulate the recovery of ecosystem multifunctionality during secondary succession of abandoned croplands in northern China.

The 'Grain-for-Green' program in China provides a valuable opportunity to investigate whether spontaneous restoration can reverse the deterioration of grassland ecosystem functions. Previous studies have focused on individual ecosystem functions, but the response of and mechanisms driving variation in ecosystem multifunctionality (EMF) during restoration are poorly understood. Here, we quantified EMF using productivity, nutrient cycling, and water regulation functions along abandoned croplands in a recovery chronosequence (5, 15 and 20 years) and in natural grasslands in the desert steppe and typical steppe. We also analyzed the effects of plant and microbial diversity and an abiotic factor (soil pH) on EMF. Our results showed that EMF increased gradually concomitant with recovery time, shifting toward EMF values comparable to those in natural grasslands in both desert and typical steppe. Similar results were found for the productivity function, the water regulation function, and soil organic carbon. However, even after 20 years of restoration, EMF did not reach the levels observed in natural grasslands. Structural equation modeling showed that the driving mechanisms of EMF differed between the two steppe types. Specifically, in the desert steppe, plant diversity, especially the diversity of perennial graminoids and perennial herbs, had a positive effect on EMF, but in the typical steppe, soil bacterial diversity had a negative effect, while soil pH had a positive effect on EMF. Our results demonstrated that spontaneous grassland restoration effectively enhanced EMF, and emphasized the importance of biodiversity and soil pH in regulating EMF during secondary succession. This work provides important insights for grassland ecosystem management in arid and semi-arid regions.

Accessing chiral sulfones bearing quaternary carbon stereocenters via photoinduced radical sulfur dioxide insertion and Truce-Smiles rearrangement.

From the viewpoint of synthetic accessibility and functional group compatibility, photoredox-catalyzed sulfur dioxide insertion strategy enables in situ generation of functionalized sulfonyl radicals from easily accessible starting materials under mild conditions, thereby conferring broader application potential. Here we present two complementary photoinduced sulfur dioxide insertion systems to trigger radical asymmetric Truce-Smiles rearrangements for preparing a variety of chiral sulfones that bear a quaternary carbon stereocenter. This protocol features broad substrate scope and excellent stereospecificity. Aside from scalability, the introduction of a quaternary carbon stereocenter at position ß to bioactive molecule-derived sulfones further demonstrates the practicality and potential of this methodology.

Tim-3/Galectin-9 signaling pathway is involved in the cytokine changes in mice with alveolar echinococcosis.

BACKGROUND: Tim-3/Galectin-9 is involved in the immune escape of many pathogens. However, the role of Tim-3/Galectin-9 in persistent infection of Echinococcus multilocularis (Em), which is related to immune escape, is still unclear. OBJECTIVE: To investigate the role of Tim-3/Galectin-9 and related cytokines in mice with persistent infection of Em. METHODS: Em infection model was established by injecting the protoscoleces. Serum was collected at days 2, 8, 30, 60, 90, 180 and 270 after infection. Lymphocytes were isolated from liver tissue samples with Ficoll. Tim-3 + CD4 + T percentage was analyzed by flow cytometry. CD4 + T cells were isolated from liver tissues of Em infected mice and cultured in vitro. The mRNA levels of Tim-3, Galectin-9, IFN-γ and IL-4 were detected by qRT-PCR. Cytokine levels in serum and culture supernatant (IFN-γ and IL-4) were analyzed by cytometric bead array. RESULTS: The expression of Tim-3 and Galectin-9 mRNA significantly increased after 30 days of infection, reached peak on day 90, and then decreased slightly on days 180-270. The expression of IFN-γ mRNA, increased on day 2 and 8 after infection, slightly decreased on days 30-60, and obvious decreased on days 90-270, but were still higher than those of the control group. The expression of IL-4 mRNA gradually increased along with the time of infection. In serum of Em infected mice, level of IFN-γ peaked at day 30 and then gradually decreased; whereas IL-4 level peaked at day 90 and then gradually decreased. In vitro experiment found that Tim-3/Galectin-9 directly caused the changes in the levels of IFN-γ and IL-4. CONCLUSIONS: Tim-3/Galectin-9 signaling pathway may be involved in the development of persistent infection of Em by regulating the production of Th1 and Th2 cytokines.

Direct arylation of N-heterocycles enabled by photoredox catalysis.

N-Heterobiaryls are common skeletons found in biological molecules, pharmaceuticals and ligands. Herein, we document an efficient and redox-neutral photocatalytic system to obtain functionalized N-heterobiaryls under mild conditions. Substrates bearing variegated functional groups are compatible with the developed photocatalytic conditions. This method is translatable to gram-scale synthesis, with a photocatalyst loading as low as 0.1 mol% and minimal variation of the yield. The starting materials are commercially available, demonstrating the practicality and accessibility of this methodology. Interestingly, phenols can serve both as coupling partners and proton donors. Arenes without a phenolic hydroxyl group also underwent efficient coupling with HFIP as a solvent.

AMP-activated kinase regulates porcine reproductive and respiratory syndrome virus infection in vitro.

Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important pathogen in the pig industry worldwide. Many viruses manipulate their cellular metabolism to replicate themselves and cause infection. A conserved cellular energy sensor, 5'-AMP-activated protein kinase (AMPK), maintains cellular energy homeostasis. We found that PRRSV infection caused significant AMPK activation in a time-dependent manner via the ROS-calcium/calmodulin-dependent protein kinase-2 pathway. RNA interference-mediated AMPK knockdown could increase PRRSV replication in MARC-145 cells, suggesting that AMPK contributed to PRRSV infection regulation. Moreover, investigation of the effect of AMPK activity on PRRSV replication showed that PRRSV replication could be suppressed by the pharmacological agonists 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside and A769662. Conversely, an AMPK inhibitor, compound C, markedly enhanced PRRSV infection. Furthermore, the AMPK agonist A769662 was found to exert no effect on PRRSV entry, assembly, and release, suggesting that A769662 may hinder the PRRSV genome replication in MARC-145 cells. In conclusion, AMPK may be a promising antiviral drug target against PRRSV infection.

GEOMETRIC STRUCTURE GUIDED MODEL AND ALGORITHMS FOR COMPLETE DECONVOLUTION OF GENE EXPRESSION DATA.

Complete deconvolution analysis for bulk RNA-seq data is important and helpful to distinguish whether the differences of disease-associated GEPs (gene expression profiles) in tissues of patients and normal controls are due to changes in cellular composition of tissue samples, or due to GEPs changes in specific cells. One of the major techniques to perform complete deconvolution is nonnegative matrix factorization (NMF), which also has a wide-range of applications in the machine learning community. However, the NMF is a well-known strongly ill-posed problem, so a direct application of NMF to RNA-seq data will suffer severe difficulties in the interpretability of solutions. In this paper, we develop an NMF-based mathematical model and corresponding computational algorithms to improve the solution identifiability of deconvoluting bulk RNA-seq data. In our approach, we combine the biological concept of marker genes with the solvability conditions of the NMF theories, and develop a geometric structures guided optimization model. In this strategy, the geometric structure of bulk tissue data is first explored by the spectral clustering technique. Then, the identified information of marker genes is integrated as solvability constraints, while the overall correlation graph is used as manifold regularization. Both synthetic and biological data are used to validate the proposed model and algorithms, from which solution interpretability and accuracy are significantly improved.

Effects of Clostridium butyricum on Growth Performance, Gut Microbiota and Intestinal Barrier Function of Broilers.

This study was conducted to evaluate the effects of Clostridium butyricum dietary supplementation on the growth, antioxidant, immune response, gut microbiota, and intestinal barrier function of broilers under high stocking density (HSD) stress. A total of 324 1-day-old Arbor Acres male broilers were randomly assigned to three treatments with six replicates, each replicate including 18 chickens (18 birds/m2). The experiment lasted 6 weeks. The three treatments were basal diet (control, CON), basal diet supplemented with 1 × 109 colony forming units (cfu)/kg C. butyricum (CB), and basal diet supplemented with 10 mg/kg virginiamycin (antibiotic, ANT). The results showed that the body weight (BW) and average daily gain (ADG) of broilers in the CB group were significantly higher than those in the CON group in three periods (p < 0.05). The total antioxidant capacity (T-AOC) and the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity in serum of the CB group were significantly increased compared with those in the CON and ANT groups at 42 days (p < 0.05). At 42 days, the serum immunoglobulin M (IgM) and immunoglobulin G (IgG) levels of the CB group were significantly higher than those of the CON group. Compared with the CON group, interleukin-1ß (IL-1ß) in the CB group was significantly decreased in the starter and grower stages (p < 0.05), but there was no significant difference between the two treatment groups (p > 0.05). C. butyricum significantly decreased the high stocking density-induced expression levels of IL-1ß and tumor necrosis factor-α (TNF-α) in the ileum of broilers at different stages. Additionally, C. butyricum could increase the expressions of claudin-1 and zonula occludens-1 (ZO-1) in intestinal tissue. Moreover, C. butyricum significantly increased the Sobs and Shannon indices in the CB group compared with the ANT group (p < 0.05), while the Ace index in the CB group was significantly higher than that of the CON group (p < 0.05). Furthermore, by using 16S rRNA gene sequencing, the proportion of Bacteroides in the CB group was increased compared to those in the CON and ANT groups at the genus level. In conclusion, C. butyricum supplemented into feed could improve the growth performance and feed utilization of broilers by promoting immune and intestinal barrier function and benefiting the cecal microflora.

Systematic Review of Smartphone Apps as a mHealth Intervention to Address Substance Abuse in Adolescents and Adults.

BACKGROUND: Substance abuse represents a foremost national concern for adolescents and adults; investigators have implemented a variety of interventions, delivered with both in-person and mobile-based apps' modalities. The electronic techniques could be more effective because they avoid the cost, privacy, and accessibility issues associated with in-person intervention. To address this issue, a systematic review of the scientific evidence relative to the efficacy of app-based interventions delivered by mobile devices (smartphones) to reduce substance abuse in adolescents and adults was carried out. METHODS: To identify relevant studies published from 2005 to 2019, a comprehensive search was conducted. Databases that were searched include CINAHL, Cochrane CENTRAL, Embase, PsycINFO, PubMed, and Web of Science. Keywords and relevant controlled vocabulary terms related to substance abuse and technology were included. Studies were included if they had examined reductions in substance abuse and problem behaviors as a primary outcome with app-based interventions delivered to adolescents and adults. RESULTS: The initial search yielded 21,641 articles, duplicates were removed, and 14,797 citations remained; title/abstract screening yielded 190 full-text articles. One hundred seventy-three were excluded because they did not meet the inclusion criteria, leaving 17 final articles to be analyzed in this review. Use of app-based interventions showed some evidence of effectiveness in reducing substance abuse in the adolescent adult population. CONCLUSION: Most intervention studies analyzed focused on alcohol reduction. Further research is needed on diverse substance abuse utilizing larger sample sizes, longitudinal studies, and theoretical foundations on the practice of delivering interventions using mobile-based apps.

Organocatalyst-controlled site-selective arene C-H functionalization.

Over the past three decades, organocatalysis has emerged as a powerful catalysis platform and has gradually been incorporated into the routine synthetic toolbox to obtain chiral molecules. However, its application in the site- and enantioselective functionalization of inactive aryl C-H bonds remains in its infancy. Here, we present an organocatalyst-controlled para-selective arene C-H functionalization strategy that addresses this issue, which remains an enduring challenge in arene functionalization chemistry. By emulating enzyme catalysis, the chiral phosphoric acid catalyst offers an ideal chiral environment for stereoinduction, and the projecting substituents give control of chemo- and site-selectivity. Various types of nucleophile are compatible with this method, affording more than 100 para-selective adducts with stereodefined carbon centres or axes in viable molecular contexts. This protocol is expected to provide a general strategy for para-selective functionalization of arene C-H bonds in a controlled manner.

Electrochemical phenothiazination of naphthylamines and its application in photocatalysis.

N-Phenylphenothiazine as an inexpensive, highly reductive and oxygen tolerant organophotocatalyst has exhibited potential in various challenging photochemical transformations. Here we report a general and straightforward method to access structurally diverse N-phenylphenothiazine derivatives by means of a novel electrochemical tool. The introduction of a 2-naphthylamine moiety with an extended π-system and an amine group led to the variation of spectral characterization. Photochemical verification experiments demonstrated that the formed N-arylation products with good efficacy and chemo/site-control displayed competitive catalytic activity in challenging transformations.

Chiral Phosphoric Acid-Catalyzed Remote Control of Axial Chirality at Boron-Carbon Bond.

The previously elusive catalytic enantioselective construction of axially chiral B-aryl-1,2-azaborines with a C-B stereogenic axis has been realized through a chiral phosphoric acid-catalyzed desymmetrization strategy reported herein. The electrophilic aromatic substitution reaction of 3,5-disubsituted phenols with diazodicarboxamides could afford these axially chiral structures in good efficiency with excellent enantiocontrol. The efficient long-range stereochemical control is achieved by multiple well-defined H-bonding interactions between chiral phosphoric acid and both substrates. Meanwhile, the reaction duration could be markedly shortened with weakly acidic N-H in 1,2-azaborine acting as H-bond donor. The scalability of the reaction and facile cleavage of the N-N bond in the product further demonstrated the practicality of this method.

Copper-Catalyzed Synthesis of Axially Chiral Biaryls with Diaryliodonium Salts as Arylation Reagents.

NOBIN and BINAM derivatives harboring biaryl frameworks are recognized as a class of important atropisomers with versatile applications. Here, we present an efficient synthetic route to access such compounds through copper-catalyzed domino arylation of N-arylhydroxylamines or N-arylhydrazines with diaryliodonium salts and [3,3]-sigmatropic rearrangement. This reaction features mild conditions, good substrate compatibility, and excellent efficiency. The practicality of this protocol was further extended by the synthesis of biaryl amino alcohols.

Metal-free oxidative cross-coupling enabled practical synthesis of atropisomeric QUINOL and its derivatives.

As an important platform molecule, atropisomeric QUINOL plays a crucial role in the development of chiral ligands and catalysts in asymmetric catalysis. However, efficient approaches towards QUINOL remain scarce, and the resulting high production costs greatly impede the related academic research as well as downstream industrial applications. Here we report a direct oxidative cross-coupling reaction between isoquinolines and 2-naphthols, providing a straightforward and scalable route to acquire the privileged QUINOL scaffolds in a metal-free manner. Moreover, a NHC-catalyzed kinetic resolution of QUINOL N-oxides with high selectivity factor is established to access two types of promising axially chiral Lewis base catalysts in optically pure forms. The utility of this methodology is further illustrated by facile transformations of the products into QUINAP, an iconic ligand in asymmetric catalysis.