Palladium-Catalyzed Three-Component Cascade Carbonylation Reaction to Construct Benzofuran Derivatives.

A novel three-component cyclization carbonylation reaction of iodoarene-tethered propargyl ethers with amine and CO is reported. This palladium-catalyzed cascade reaction undergoes a sequence of oxidative addition, unsaturated bond migration, carbonyl insertion, and nucleophilic attack to deliver the benzofuran skeleton. Both aromatic amines and aliphatic amines could proceed smoothly in this transformation under one atm of CO.

Fluoride-Mediated Aryne 1,2-Difunctionalization Involving C═S Bond Heterolysis.

We have successfully synthesized a series of bidentate ligands by utilizing 2-(trimethylsilyl)phenyl trifluorosulfonate as a precursor for the benzyl group. This method proceeded by inserting a polythiourea into the C═S π-bond, intramolecular ring proton migration, and ring opening. Salient features of this strategy are mild reaction conditions, a novel product structure, excellent stereochemistry, and a good functional group tolerance. Furthermore, a series of density functional theory calculations were performed to gain insights into the transfer mechanism.

Discovery of Novel Diphenyl Acrylonitrile Derivatives That Promote Adult Rats' Hippocampal Neurogenesis.

We previously discovered WS-6 as a new antidepressant in correlation to its function of stimulating neurogenesis. Herein, several different scaffolds (stilbene, 1,3-diphenyl 1-propene, 1,3-diphenyl 2-propene, 1,2-diphenyl acrylo-1-nitrile, 1,2-diphenyl acrylo-2-nitrile, 1,3-diphenyl trimethylamine), further varied through substitutions of twelve amide substituents plus the addition of a methylene unit and an inverted amide, were examined to elucidate the SARs for promoting adult rat neurogenesis. Most of the compounds could stimulate proliferation of progenitors, but just a few chemicals possessing a specific structural profile, exemplified by diphenyl acrylonitrile 29b, 32a, and 32b, showed better activity than the clinical drug NSI-189 in promoting newborn cells differentiation into mature neurons. The most potent diphenyl acrylonitrile 32b had an excellent brain AUC to plasma AUC ratio (B/P = 1.6), suggesting its potential for further development as a new lead.

Nickel-Catalyzed Three-Component Tandem Radical Cyclization 1,5-Difunctionalization of 1,3-Enynes and Alkyl Bromide.

A nickel-catalyzed three-component tandem radical cyclization reaction of aryl bromides with 1,3-enynes and aryl boric acids to construct γ-lactam-substituted allene derivatives has been described. This protocol provides lactam alkyl radicals through the free radical cyclization process, which can be effectively used to participate in the subsequent multicomponent coupling reaction so that 1,3-enynes could directly convert into corresponding poly-substituted allene compounds. In addition, this efficient method enjoys a broad substrate scope and provides a series of 1,5-difunctionalized allenes in a one-pot reaction.

Synthesis of C4-Aminated Carbazoles and Their Derivatives via Pd/NBE Chemistry.

Carbazole, as one of the most important organic frameworks, has been used in optoelectronic materials and biochemistry. However, the synthesis of C4-substituted carbazole has always been an unsolved problem. This report describes the one-step synthesis of C4-aminated carbazoles and their derivatives through the series reaction of C-H amination and arylation. The substrate scope is wide. C4-Amino carbazoles substituted by C2, C6, C7, and C8 methyl groups, especially carbazole derivatives of fused rings, pyridine, and dibenzofuran, can be synthesized.

Template Synthesis to Solve the Unreachable Ortho C-H Functionalization Reaction of Aryl Iodide.

This report describes the use of a simple Pd/NBE catalytic system to achieve ortho C-H oxylation and phosphonylation and other functionalizations of aryl iodide through templated conversion reactions. Dimethylamine is introduced in the ortho-site of aryl iodide through C-H amination, and aryl dimethylamine is quickly converted to methyl quaternary ammonium salt precipitation. Methyl quaternary ammonium salt avoids Hofmann elimination in subsequent functionalization. This method solves various ortho functionalization reactions of aryl iodide that have not been achieved for a long time in the field of Pd/NBE chemistry indirectly.

Direct synthesis of phosphorotrithioates from [TBA][P(SiCl3)2] and disulfides.

Sulfur-containing organophosphorus molecules have played a pivotal role in organic synthesis, pharmaceutical pesticides and functional materials, thereby motivating researchers worldwide to establish S-P bonds from more environmentally friendly phosphorus sources. In this study, a novel method was developed for constructing S-P bonds, specifically by reacting the inorganic phosphorus derivative TBA[P(SiCl3)2] with sulfur-containing compounds under mild conditions. This method demonstrates the advantages of low energy consumption, mild reaction conditions and environmental friendliness. Moreover, this protocol-as a green synthesis method to replace the use of white phosphorus in the production of organophosphorus compounds (OPCs)-achieved the functional conversion of "inorganic phosphorus to organic phosphorus", in line with the national green development strategy.

Synthesis of 3(2H)-furanone derivatives: p-TsOH/halotrimethylsilane promoted cycloketonization of γ-hydroxyl ynones.

A p-TsOH/halotrimethylsilane facilitated cycloketonization of γ-hydroxyl ynones is detailed. This methodology enables the one-step synthesis of polysubstituted 3(2H)-furanone products. It is remarkable that the reaction exhibits excellent regio- and chemoselectivity by the addition of very small quantities of p-toluenesulfonic acid and water.

Analysis of the Levels of Vitamin A, D and E in Peripheral Blood of Children in Zhejiang Province.

BACKGROUND: This study aims to investigate the serum fat-soluble vitamins A, D, and E levels of children in Zhejiang Province, and to provide a reference range of fat-soluble vitamins for children in Zhejiang Province. METHODS: Between May 2019 and December 2019, 871 children who sent peripheral blood samples to Hangzhou Biozon Medical Institute Co., Ltd. for fat-soluble vitamin A, D, and E analysis were selected, including 432 boys and 439 girls. After the peripheral blood was collected, the serum A, D, and E levels were measured, and the differences in age, gender, season, and region were compared. RESULTS: With age, the level of vitamin A gradually increased (p < 0.01), and vitamin D2, D3, and total vitamin D all increased first and then decreased. Vitamin A (131.79 ± 47.05 ng/mL vs. 121.96 ± 41.01 ng/mL) and E (5.87 ± 2.23 µg/mL vs. 5.56 ± 2.13 µg/mL) levels of girls were higher than boys (p < 0.01), and vitamin D3 (15.25 ± 6.16 ng/mL vs.15.17 ± 7.26 ng/mL) and total vitamin D (18.09 ± 7.01 ng/mL vs. 17.03 ± 8.79 ng/mL) levels of boys were higher than girls (p < 0.01). From the perspective of regional distribution, the levels of vitamin A, D2, and E in Ningbo were higher than those in Hangzhou and other regions. The seasonal distribution of vitamin A and E levels were highest in summer, while vitamin D3 and D levels were highest in fall. The average vitamin concentrations were as follows: vitamin A was (126.81 ± 44.42) ng/mL; vitamin D2 was (1.84 ± 3.16) ng/mL, vitamin D3 was (15.71 ± 6.75) ng/mL, total vitamin D was (17.55 ± 7.91) ng/mL, and vitamin E was (5.72 ± 2.19) µg/mL. The reference value ranges of vitamin A, D2, D3, D, and E were (52.44 - 222.27) ng/mL, (0.01 - 11.66) ng/mL, (4.92 - 30.96) ng/mL, (4.92 - 30.96) ng/mL, and (2.66 - 10.92) µg/mL, respectively. CONCLUSIONS: The childrens' fat soluble vitamin levels in Zhejiang province show significant differences in age, gender, season, and regional distribution. Corresponding reference standards should be formulated as soon as possible, and vitamin supplements should be targeted and reasonable to ensure the healthy development of children.

Development and Validation of a Species-specific PCR Method for the Identification of Ginseng Species Using Orthogonal Approaches.

When testing botanical ingredients of herbal medicines and dietary supplements, the complexity of botanical matrixes often requires the use of orthogonal methods to establish identification procedures suitable for quality control purposes. Genomic-based botanical identification methods are evolving and emerging as useful quality control tools to complement traditional morphological and chemical identification methods. Species-specific polymerase chain reaction methods are being evaluated for botanical quality control and as a cost-effective approach to identify and discriminate between closely related botanical species. This paper describes orthogonal identification of Panax ginseng, P. quinquefolius, and P. notoginseng materials in commerce as an example of the development and validation of a set of species-specific polymerase chain reaction methods to establish botanical identity in ginseng roots. This work also explored the possibility of extending the application of species-specific polymerase chain reaction methods to provide species identity information for processed materials, such as steamed roots and hydroalcoholic extracts, and showed success with this approach. Finally, the paper provides recommendations for an out-of-specification investigation of samples that may pass some of the orthogonal tests and fail others.

The use of intraoperative transit time flow measurement can reduce postoperative myocardial injury.

OBJECTIVE: This study investigates the relationship between the use of transit time flow measurement (TTFM) and postoperative myocardial injury in off-pump coronary artery bypass grafting (OPCABG). METHODS: In this retrospective study, we collected basic data from patients hospitalized for OPCABG in the Department of Cardiothoracic Surgery, Changzhou Second People's Hospital Affiliated with Nanjing Medical University. According to the academic research consortium (ARC)-2 definition of significant myocardial injury, we used cardiac troponin I >2380 ng/L as a criterion for significant postoperative myocardial injury. We use logistic regression and forest plots to assess the association of TTFM use with myocardial injury outcomes. RESULTS: One hundred and forty-six patients were included in this study. The overall median age of these patients was 65.05 years, and 32 (21.92%) experienced a postoperative myocardial injury. TTFM was independently associated with the incidence of postoperative myocardial injury (odds ratio = 0.34 [95% confidence interval = 0.15-0.78]; p = .01), and we found similar trends in regression analyses across subgroups of sex, age, number of bridging vessels, hypertension, diabetes mellitus, BMI, and percutaneous coronary revascularization. One hundred and six patients were followed for 1-year vessel permeability, and seven patients (6.6%) were occluded. CONCLUSIONS: The use of TTFM is independently associated with a reduced incidence of postoperative myocardial lesions during off-pump coronary bypass surgery. The TTFM procedure in OPCABG deserves to be actively promoted to reduce the incidence of postoperative myocardial injury.

Genome-wide analysis of butterfly bush (Buddleja alternifolia) in three uplands provides insights into biogeography, demography and speciation.

Understanding processes that generate and maintain large disjunctions within plant species can provide valuable insights into plant diversity and speciation. The butterfly bush Buddleja alternifolia has an unusual disjunct distribution, occurring in the Himalaya, Hengduan Mountains (HDM) and the Loess Plateau (LP) in China. We generated a high-quality, chromosome-level genome assembly of B. alternifolia, the first within the family Scrophulariaceae. Whole-genome re-sequencing data from 48 populations plus morphological and petal colour reflectance data covering its full distribution range were collected. Three distinct genetic lineages of B. alternifolia were uncovered, corresponding to Himalayan, HDM and LP populations, with the last also differentiated morphologically and phenologically, indicating occurrence of allopatric speciation likely to be facilitated by geographic isolation and divergent adaptation to distinct ecological niches. Moreover, speciation with gene flow between populations from either side of a mountain barrier could be under way within LP. The current disjunctions within B. alternifolia might result from vicariance of a once widespread distribution, followed by several past contraction and expansion events, possibly linked to climate fluctuations promoted by the Kunlun-Yellow river tectonic movement. Several adaptive genes are likely to be either uniformly or diversely selected among regions, providing a footprint of local adaptations. These findings provide new insights into plant biogeography, adaptation and different processes of allopatric speciation.

Synthesis, structural characterization, molecular docking study, biological activity of carbon monoxide release molecules as potent antitumor agents.

In this study, two series of novel carbon monoxide-releasing molecules (CO-RMs) containing Co were designed and synthesized. The synthesized complexes were characterized by IR, ESI-MS, 1H NMR and 13C NMR spectroscopies. The antitumor activity of all complexes on HepG2 cells, Hela cells and MDA-MB-231 cells were assayed by MTT. IC50 values of complexes 1-13 were 4.7-548.6 µM. Among these complexes, complex 1 was presented with a high selectivity to HepG2 cells (IC50 = 4.7 ± 0.76 µM). Compared with iCORM (inactive CORM), CORM (complex 1) showed a remarkable activity against tumor cells owing to co-effect of CO and the ligand of COX-2 inhibitor. In addition, complex 1 increased ROS in mitochondria and caused a decrease of dose-dependent mitochondrial membrane potential against HepG2 cells. Complex 1 down-regulated the expression of COX-2 protein in western blot analysis. The molecular docking study suggested that the complex 1 formed a hydrogen bond with amino acid R120 in the active site of the Human cyclooxygenase-2 (COX-2). Therefore, the complex 1 could induce apoptosis of HepG2 cells through targeting COX-2 and mitochondria pathways, and it maybe a potential therapeutic agent for cancer.

AgSCF3/Na2S2O8-Promoted Trifluoromethylthiolation/Cyclization of o-Propargyl Arylazides/ o-Alkynyl Benzylazides: Synthesis of SCF3-Substituted Quinolines and Isoquinolines.

A AgSCF3/Na2S2O8-promoted trifluoromethylthiolation/cascade cyclization of o-propargyl arylazides (or o-alkynyl benzylazides) triggered by a carbon-carbon triple bond is reported. This strategy provides the synthesis of valuable SCF3-substituted quinoline and isoquinoline systems via the construction of one C(sp2)-SCF3 bond and one C-N bond within one process.

The solvent-controlled chemoselective construction of C-S/S-S bonds via the Michael reaction/thiol coupling of quinoline-2-thiones.

K2CO3-catalyzed thio-Michael addition using quinoline-2-thiones and α,ß-unsaturated carbonyl compounds was used to assess the chemoselective construction of C-S and S-S bonds under mild reaction conditions in different solvents. The C-S bond showed a better chemoselective construction in EtOH whereas the S-S bond showed a better chemoselective construction in 1,4-dioxane. The corresponding products, generated from the reaction, presented a significant solvent-controlling effect.

Efficient synthesis of esters through oxone-catalyzed dehydrogenation of carboxylic acids and alcohols.

Since esters are important organic synthesis intermediates, an environmentally friendly oxone catalyzed-esterification of carboxylic acids with alcohols has been developed. A series of carboxylic acid esters are obtained in high yield. This strategy requires mild reaction conditions, providing an attractive alternative for the construction of valuable carbonyl esters. Electron-rich and electron-deficient groups are compatible with the standard conditions and a variety of substrates are demonstrated. Moreover, the reaction could easily be adapted to typical prodrugs, drugs and gram-scale synthesis.

An Efficient Amide-Aldehyde-Alkene Condensation: Synthesis for the N-Allyl Amides.

The allylamine skeleton represents a significant class of biologically active nitrogen compounds that are found in various natural products and drugs with well-recognized pharmacological properties. In this personal account, we will briefly discuss the synthesis of allylamine skeletons. We will focus on showing a general protocol for Lewis acid-catalyzed N-allylation of electron-poor N-heterocyclic amides and sulfonamide via an amide-aldehyde-alkene condensation reaction. The substrate scope with respect to N-heterocyclic amides, aldehydes, and alkenes will be discussed. This method is also capable of preparing the Naftifine motif from N-methyl-1-naphthamide or methyl (naphthalene-1-ylmethyl)carbamate, with paraformaldehyde and styrene in a one-pot manner.

Copper(i) chloride promoted Csp(2)-N cross-coupling of 1,2-di(pyrimidin-2-yl) disulfides with amines: an efficient approach to obtain C2-amino functionalized pyrimidines.

The copper(i)-promoted cross-coupling of 1,2-di(pyrimidin-2-yl) disulfides with aromatic amines and aliphatic amines to deliver C-N coupling products in moderate to good yields is reported in this paper. Central to this strategy is the conversion of disulfides into aryl- and alkyl amines by a copper-promoted chemoselective C-S bond cleavage.

MicroRNA-212 inhibits osteosarcoma cells proliferation and invasion by down-regulation of Sox4.

BACKGROUND: Multiple MicroRNAs (miRNAs) have been identified in the development and progression of osteosarcoma. However, the expression and roles of miR-212 in osteosarcoma remain largely undefined. METHODS: Real-time PCR assays were used to detect the expression of miR-212 in human osteosarcoma tissues. MiR-212 mimics were introduced into MG63 and U2OS cells. Bioinformatic prediction was used to identify the potential targets of miR-212. Protein expression analysis, luciferase assays and rescue assays were used to confirm the substrate of miR-212. RESULTS: miR-212 was significantly down-regulated in human osteosarcoma tissues, compared with adjacent normal tissues. Introduction of miR-212 mimics into MG63 and U2OS cells inhibited cell proliferation and invasion. Besides, miR-212 overexpression could also inhibit tumor growth in the nude mice. Additionally, bioinformatic prediction suggested that the sex-determining region Y-box 4 (Sox4) is a target gene of miR-212. Sox4 inhibition phenocopied the roles of miR-212, while restored expression of Sox4 dampened miR-212-mediated suppression of tumor progression. CONCLUSION: The miR-212/Sox4 interaction plays an important role of in the osteosarcoma progression.

Interaction between hydroxymethanesulfonic acid and several organic compounds and its atmospheric significance.

The interactions of the micro-mechanism of hydroxymethanesulfonic acid (HMSA) with the typical small organic molecule in atmospheric (X = methanol, formaldehyde, formic acid, methyl formate, dimethyl ether, acetone) has been investigated by density functional theory (DFT), quantum theory of atoms in molecules (QTAIM), Generalized Kohn-Sham Enery Decomposition Analysis (GKS-EDA) and the atmospheric clusters dynamic code (ACDC). The results of DFT show that the stable six- to eight-membered ring structures are easily formed in HMSA-X clusters. According to the topological analysis results of the AIM theory and the IRI method, a strong hydrogen bonding interaction is present in the complex. GKS-EDA results show that electrostatic energy is the main contributor to the interaction energy as it accounts for 51 %-55 % of the total attraction energy. The evaporation rates of HMSA-HMSA and HMSA-HCOOH clusters were much lower than those of the other HMSA complexes. In addition, the Gibbs energy of formation (ΔG) of HMSA-X dimers is investigated under atmosphere temperature T = 217-298 K and p = 0.19-1.0 atm, the ΔG decreased with decreasing of the atmosphere temperature and increased with the decrease of atmospheric pressure, indicating that the low temperature and high pressure may significantly facilitate to the formation of dimers.