Silver-Catalyzed, Aldehyde-Induced α-C-H Functionalization of Tetrahydroisoquinolines with Concurrent C-P Bond Formation/N-Alkylation.

The first facile and efficient silver-catalyzed, aldehyde-induced three-component reaction of N-unprotected tetrahydroisoquinolines, aldehydes, and dialkyl phosphonates has been developed, providing a general one-step approach to structurally diverse C1-phosphonylated THIQs accompanied by concurrent C-P bond formation/N-alkylation with remarkable functional group tolerance and excellent regioselectivity for endo products.

Palladium-Catalyzed Domino Addition and Cyclization of Arylboronic Acids with 3-Hydroxyprop-1-yn-1-yl Phosphonates Leading to 1,2-Oxaphospholenes.

A novel and efficient palladium-catalyzed domino addition-cyclization of a wide range of arylboronic acids with various 3-hydroxyprop-1-yn-1-yl phosphonates has been developed, affording a convenient and powerful tool for the preparation of valuable 1,2-oxaphospholenes with mild reaction conditions, broad substrate applicability, and good to excellent yields. Mechanistic studies revealed that the reaction might involve Michael addition and nucleophilic substitution.

Ag-mediated cascade decarboxylative coupling and annulation: a convenient route to 2-phosphinobenzo[b]phosphole oxides.

The first facile and practical silver-mediated cascade reaction of arylpropiolic acids with diarylphosphine oxides has been developed, providing a general, one step approach to structurally sophisticated 2-phosphinobenzo[b]phosphole oxide frameworks of importance in materials science via sequential decarboxylative C-P cross-coupling and C-H/P-H functionalization with operational simplicity and excellent functional group compatibility.

Palladium-catalyzed Suzuki cross-coupling of arylhydrazines via C-N bond cleavage.

The first example of Pd-catalyzed Suzuki cross-coupling of readily available arylhydrazines with arylboronic acids via C-N bond cleavage was developed under air, affording various biaryl compounds with broad substrate applicability and moderate to good yields. Moreover, the rigorous exclusion of air/moisture is not required in these transformations. Thus, the protocol represents a simple and efficient procedure to access biaryl compounds.

Palladium-catalyzed air-based oxidative coupling of arylboronic acids with H-phosphine oxides leading to aryl phosphine oxides.

We present a novel and highly efficient methodology that allows for the construction of C-P bonds via the palladium-catalyzed air-based oxidative coupling of various commercially available arylboronic acids with easily oxidized H-phosphine oxides leading to valuable aryl phosphine oxides, particularly triarylphosphine oxides, with the use of air as the green oxidant, broad substrate applicability and good to excellent yields. The described catalytic system should be an efficient complement to the Chan-Lam type reaction and be useful in synthetic programs.

Danshen injection mitigated the cerebral ischemia/reperfusion injury by suppressing neuroinflammation via the HIF-1α/CXCR4/NF-κB signaling pathway.

Danshen injection (DI) is effective in treating cardiovascular and cerebrovascular diseases, including ischemic stroke (IS), including IS, but its mechanism is unclear. A middle cerebral artery occlusion model was used to simulate ischemia/reperfusion (I/R) injury in SD rats. Overexpression of hypoxia-inducible factor 1α (HIF-1α) was achieved by AAV-HIF-1α. Rats were treated with DI or saline. Neurological scores and infarction rates were assessed. I/R damage was examined by HE, 2,3,5-triphenyltetrazolium and Nissl stainings. Expression levels of relative proteins [TNF-α, IL-6, IL-1ß, SOD, MDA, ROS, HIF-1α, CXC chemokine receptor 4 (CXCR4) and NF-κB] were measured. DI treatment improved neurological scores and reduced infarction rates, suggesting that it inhibits inflammation and oxidative stress. The expression levels of HIF-1α, CXCR4 and NF-κB were decreased. However, the effectiveness of DI on inflammation inhibition was lost after HIF-1α overexpression. DI may directly target HIF-1α to suppress neuroinflammation and reduce I/R injury by suppressing the HIF-1α/CXCR4/NF-κB signaling pathway.

HIF-1α knockdown attenuates inflammation and oxidative stress in ischemic stroke male rats via CXCR4/NF-κB pathway.

BACKGROUND: Hypoxia inducible factor-1α (HIF-1α) is a sensitive indicator of oxygen homeostasis, of which the expression elevates following hypoxia/ischemia. This study reveals the specific mechanisms underlying the effects of HIF-1α on ischemic stroke (IS). METHODS: IS model was established using middle cerebral artery occlusion (MCAO)-modeled male rats and oxygen glucose deprivation/reoxygenation (OGD/R)-treated mice hippocampal cells HT22, followed by the silencing of HIF-1α and the overexpression of C-X-C motif chemokine receptor 4 (CXCR4) and nuclear factor-kappa B (NF-κB). Following the surgery, Garcia's grading scale was applied for neurological evaluation. Cerebral infarcts and injuries were visualized using 2,3,5-triphenyltetrazolium chloride and hematoxylin-eosin staining. The levels of tumor necrosis factor-α, Interleukin (IL)-6, IL-1ß, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine, were calculated via ELISA. MTT assay and lactate dehydrogenase (LDH) assay kit were adopted to determine the viability and cytotoxicity of OGD/R-modeled cells. Reactive oxygen species (ROS) generation was evaluated using a 2'-7'dichlorofluorescin diacetate (DCFH-DA) probe. The levels of HIF-1α, CXCR4, and NF-κB p65 were quantified via Western blot and immunofluorescence, respectively. RESULTS: HIF-1α knockdown improved Garcia's score, attenuated the cerebral infarct, inflammation, and ROS generation, and alleviated the levels of inflammatory cytokines and CXCR4/NF-κB p65 in MCAO-modeled rats. Such effects were reversed following the overexpression of CXCR4 and NF-κB. Also, in OGD/R-treated HT22 cells, HIF-1α silencing diminished the cytotoxicity and ROS production and reduced the expressions of CXCR4/NF-κB p65, while promoting viability. However, CXCR4/NF-κB p65 overexpression did the opposite. CONCLUSION: HIF-1α knockdown alleviates inflammation and oxidative stress in IS through the CXCR4/NF-κB pathway.

Integrated Analysis of miRNA and mRNA Expression Profiles Reveals the Molecular Mechanism of Posttraumatic Stress Disorder and Therapeutic Drugs.

Purpose: Post-traumatic stress disorder (PTSD) is a result of trauma exposure and is related to psychological suffering as a long-lasting health issue. Further analysis of the networks and genes involved in PTSD are critical to the molecular mechanisms of PTSD. Methods: In this study, we aimed to identify key genes and molecular interaction networks involved in the pathogenesis of PTSD by integrating mRNA and miRNA data. Results: By integrating three high-throughput datasets, 5606 differentially expressed genes (DEGs) were detected, including five differentially expressed miRNAs (DEmiRNAs) and 5525 differentially expressed mRNAs (DEmRNAs). Nineteen upregulated and 46 downregulated DEmRNAs were identified in both GSE64813 and GSE89866 datasets, while five upregulated DEmiRNAs were found in the GSE87768 dataset. Functional annotations of these DEmRNAs indicated that they were mainly enriched in blood coagulation, cell adhesion, platelet activation, and extracellular matrix (ECM)-receptor interaction. Integrated protein-protein and miRNA-protein interaction networks among the DEGs were established with the help of 65 nodes and 121 interactions. Finally, 286 small molecules were obtained based on the Drug-Gene Interaction database (DGIdb). Three genes, prostaglandin-endoperoxide synthase 1 (PTGS1), beta-tubulin gene (TUBB1), and cyclin-dependent kinase inhibitor 1A (CDKN1A), were the most promising targets for PTSD therapy. Additionally, the present study also provided a higher performance diagnostic model for PTSD based on 17 DEmRNAs, which was validated in two independent datasets, GSE109409 and GSE63878. Conclusion: Our data provides a new molecular aspect that ECM-receptor interaction and the platelet activation process could be the potential molecular mechanism of PTSD, and the genes involved in this process may be promising therapeutic targets. A higher-performance diagnostic model for PTSD has also been identified.

Copper-Catalyzed Direct Coupling of Unprotected Propargylic Alcohols with P(O)H Compounds: Access to Allenylphosphoryl Compounds under Ligand- and Base-Free Conditions.

The first facile and efficient copper-catalyzed direct C-P cross-coupling of unprotected propargylic alcohols with P(O)H compounds has been developed, providing a general, one-step approach to construct valuable allenylphosphoryl frameworks with operational simplicity and high step- and atom-economy under ligand-, base-, and additive-free conditions.

TBAI-catalyzed oxidative C-H functionalization: a new route to benzo[b]phosphole oxides.

The first metal-free, efficient TBAI-catalyzed radical addition/cyclization of diaryl(arylethynyl)phosphine oxides with toluene derivatives has been developed, affording a general, one-step approach to structurally sophisticated benzo[b]phosphole oxides via sequential C-H functionalization along with the formation of two new C-C bonds.

Crystal structure of (5'S,8'S)-3-(2,5-di-methyl-phen-yl)-8-meth-oxy-3-nitro-1-aza-spiro-[4.5]decane-2,4-dione.

The title compound, C18H22N2O5, was synthesized by nitrification of its enol precursor. The pyrrolidine ring plane adopts a twisted conformation about the C-C bond linking the spiro centre and the C=O group remote from the N atom. It makes dihedral angles of 71.69 (9) and 88.92 (9)°, respectively, with the benzene ring plane and the plane defined by the four C atoms that form the seat of the of the cyclo-hexane chair. At the spiro centre, the NH group is axial and the C=O group is equatorial with respect to the cyclo-hexane ring. In the crystal, inversion dimers linked by pairs of N-H⋯O hydrogen bonds generate R 2 (2)(8) loops. The dimers are linked by C-H⋯O inter-actions, generating a three-dimensional network.

Copper-catalyzed decarboxylative C-P cross-coupling of alkynyl acids with H-phosphine oxides: a facile and selective synthesis of (E)-1-alkenylphosphine oxides.

A novel and efficient copper-catalyzed decarboxylative cross-coupling of alkynyl acids for the stereoselective synthesis of E-alkenylphosphine oxides has been developed. In the presence of 10 mol % of CuCl without added ligand, base, and additive, various alkynyl acids reacted with H-phosphine oxides to afford E-alkenylphosphine oxides with operational simplicity, broad substrate scope, and the stereoselectivity for E-isomers.

Nickel-catalyzed C-P cross-coupling of arylboronic acids with P(O)H compounds.

A novel and efficient Ni-catalyzed coupling of a wide range of arylboronic acids with H-phosphites, H-phosphinate esters, and H-phosphine oxides has been developed, providing a general and powerful tool for the synthesis of various aryl-phosphorus compounds, especially for valuable triarylphosphine oxides, in good to excellent yield. This protocol is the first Ni-catalyzed C-P bond-forming reaction between arylboronic acids and P(O)H compounds.