Anti-inflammation is an important way that Qingre-Huazhuo-Jiangsuan recipe treats acute gouty arthritis.

Background: Acute gouty arthritis (AGA) significantly impairs patients' quality of life. Currently, existing therapeutic agents exhibit definite efficacy but also lead to serious adverse reactions. Therefore, it is essential to develop highly efficient therapeutic agents with minimal adverse reactions, especially within traditional Chinese medicine (TCM). Additionally, food polyphenols have shown potential in treating various inflammatory diseases. The Qingre-Huazhuo-Jiangsuan-Recipe (QHJR), a modification of Si-Miao-San (SMS), has emerged as a TCM remedy for AGA with no reported side effects. Recent research has also highlighted a strong genetic link to gout. Methods: The TCM System Pharmacology (TCMSP) database was used to collect the main chemical components of QHJR and AGA-related targets for predicting the metabolites in QHJR. HPLC-Q-Orbitrap-MS was employed to identify the ingredients of QHJR. The collected metabolites were then used to construct a Drugs-Targets Network in Cytoscape software, ranked based on their "Degree" of significance. Differentially expressed genes (DEGs) were screened in the Gene Expression Omnibus (GEO) database using GEO2R online analysis. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. The DEGs were utilized to construct a Protein-Protein Interaction (PPI) Network via the STRING database. In vivo experimental validation was conducted using colchicine, QHJR, rapamycin (RAPA), and 3-methyladenine (3-MA) as controls to observe QHJR's efficacy in AGA. Synovial tissues from rats were collected, and qRT-PCR and Western blot assays were employed to investigate Ampk-related factors (Ampk, mTOR, ULK1), autophagy-related factors (Atg5, Atg7, LC3, p62), and inflammatory-related factors (NLRP3). ELISA assays were performed to measure inflammatory-related factor levels (IL-6, IL-1ß, TNF-α), and H&E staining was used to examine tissue histology. Results: Network analysis screened out a total of 94 metabolites in QHJR for AGA. HPLC-Q-Orbitrap-MS analysis identified 27 of these metabolites. Notably, five metabolites (Neochlorogenic acid, Caffeic acid, Berberine, Isoliquiritigenin, Formononetin) were not associated with any individual herbal component of QHJR in TCMSP database, while six metabolites (quercetin, luteolin, formononetin, naringenin, taxifolin, diosgenin) overlapped with the predicted results from the previous network analysis. Further network analysis highlighted key components, such as Caffeic acid, cis-resveratrol, Apigenin, and Isoliquiritigenin. Other studies have found that their treatment of AGA is achieved through reducing inflammation, consistent with this study, laying the foundation for the mechanism study of QHJR against AGA. PPI analysis identified TNF, IL-6, and IL-1ß as hub genes. GO and KEGG analyses indicated that anti-inflammation was a key mechanism in AGA treatment. All methods demonstrated that inflammatory expression increased in the Model group but was reversed by QHJR. Additionally, autophagy-related expression increased following QHJR treatment. The study suggested that AMPKα and p-AMPKα1 proteins were insensitive to 3 MA and RAPA, implying that AMPK may not activate autophagy directly but through ULK1 and mTOR. Conclusion: In conclusion, this study confirms the effectiveness of QHJR, a modified formulation of SMS (a classic traditional Chinese medicine prescription for treating gout), against AGA. QHJR, as a TCM formula, offers advantages such as minimal safety concerns and potential long-term use. The study suggests that the mechanism by which QHJR treats AGA may involve the activation of the AMPK/mTOR/ULK1 pathway, thereby regulating autophagy levels, reducing inflammation, and alleviating AGA. These findings provide new therapeutic approaches and ideas for the clinical treatment of AGA.

C(alkyl)-C(vinyl) bond cleavage enabled by Retro-Pallada-Diels-Alder reaction.

Activation and cleavage of carbon-carbon (C-C) bonds is a fundamental transformation in organic chemistry while inert C-C bonds cleavage remains a long-standing challenge. Retro-Diels-Alder (retro-DA) reaction is a well-known and important tool for C-C bonds cleavage but less been explored in methodology by contrast to other strategies. Herein, we report a selective C(alkyl)-C(vinyl) bond cleavage strategy realized through the transient directing group mediated retro-Diels-Alder reaction of a six-membered palladacycle, which is obtained from an in situ generated hydrazone and palladium hydride species. This unprecedented strategy exhibits good tolerances and thus offers new opportunities for late-stage modifications of complex molecules. DFT calculations revealed that an intriguing retro-Pd(IV)-Diels-Alder process is possibly involved in the catalytic cycle, thus bridging both Retro-Diels-Alder reaction and C-C bond cleavage. We anticipate that this strategy should prove instrumental for potential applications to achieve the modification of functional organic skeletons in synthetic chemistry and other fields involving in molecular editing.

Silver-Catalyzed Direct Nucleophilic Cyclization: Enantioselective De Novo Synthesis of C-C Axially Chiral 2-Arylindoles.

Atropisomeric indoles widely exist in natural products, pharmaceuticals, functional materials, and catalysts for their featured biological activities, photoelectric properties, and catalytic activities, while facile and de novo construction of this motif remains underexplored. Herein, we report a chiral silver phosphate-catalyzed direct 5-endo-dig nucleophilic cyclization of 2-alkynylanilins under mild conditions, affording various C-C axially chiral 2-arylindoles in high to excellent yields and enantioselectivities. Control experiments implied the cooperative catalysis of AgOAc and chiral phosphoric acid, wherein the former accelerated the desired transformation while the latter improved the enantioselectivity. In addition, as the first example of silver-catalyzed enantioselective de novo synthesis of C-C axially chiral indole skeletons, synthetic applications and products' thermal stability have been investigated.

Qingre Huazhuo Jiangsuan Decoction promotes autophagy by inhibiting PI3K/AKT/mTOR signaling pathway to relieve acute gouty arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Gout belongs to the category of "arthralgia syndrome" in traditional Chinese medicine. It is believed that gout is caused by stagnation of blood stasis, heat, and turbid toxin. Qingre Huazhuo Jiangsuan Decoction (QHJD) is a traditional Chinese medicine prescription developed from the classic Chinese medicine prescription Simiao powder to clear heat, remove turbidity, reduce acid, and reduce inflammation. Now Traditional Chinese Medicine (TCM) physicians often apply it to treat acute gouty arthritis (AGA). However, the mechanism of QHJD in relieving acute gouty arthritis is still unclear, and further research is needed. AIM OF THE STUDY: Here, we aim to explore the potential mechanism of QHJD in relieving acute gouty arthritis. MATERIALS AND METHODS: Acute gouty arthritis model was established by injecting monosodium urate (MSU) suspension into knee joint. The pathological state of synovial tissue in each group was evaluated by hematoxylin-eosin (HE) staining. The level of TNF-α, IL-6, and IL-1ß were detected by enzyme-linked immunosorbent assay (ELISA). qRT-PCR was used to detect the mRNA expression of NLRP3, ATG5, ATG7, PI3K, AKT, and mTOR. The protein expression of LC3II/I, p62, ULK1, P-ULK1, Beclin-1, PI3K, AKT, mTOR, P-PI3K, P-AKT, and P-mTOR were detected by Western blot. RESULTS: (1) The level of autophagy protein (mRNA) was significantly up-regulated in QHJD group and rapamycin, while the expression of autophagy protein (mRNA) was significantly downregulated in the 3-methyladenoenoic acid (3 MA) group; (2) QHJD and rapamycin significantly inhibited PI3K/AKT/mTOR pathway, while 3 MA group activated this pathway. (3) It was worth noting that after treatment with QHJD and rapamycin, the inflammatory pathological state of AGA synovial tissue was significantly reduced with the activation of the autophagy gene in knee synovial tissue, and the inhibition of PI3K/AKT/mTOR pathway. CONCLUSIONS: This research revealed that QHJD activates autophagy by inhibiting PI3K/AKT/mTOR pathway, thereby relieving acute gouty arthritis.

A Chinese classical prescription Qianjinweijing Decoction in treatment of lung cancer: An overview.

Lung cancer is one of the most common malignant tumors in the world, and its incidence and mortality rate rank among the top malignant tumors worldwide, which has become an important killer threatening human survival rate and well-being. Modern medical treatment for lung cancer is mainly based on surgery and radiotherapy, with gene, targeted drugs and immunotherapy as auxiliary treatments, which are effective, but there are problems such as postoperative recurrence, resistance to radiotherapy, toxic side effects and poor compliance. In recent years, with the continuous development of TCM, TCM is popular among physicians and patients for its high efficiency, low toxicity, low side effects and economic benefits, etc. As a classical TCM formula, Qianjin Weijin Decoction(QJWJ) has certain value in the treatment of lung cancer. This paper summarizes and analyzes the clinical research, molecular mechanism, pharmacological effects and chemical composition of QJWJ in the treatment of lung cancer, in order to provide more ideas and theoretical basis for the treatment of lung cancer with QJWJ.

Establishment of a human iPSC line (SUTCMi001-A) derived from a healthy donor.

This study describes the characterization of one induced pluripotent stem cell line (iPSC) from a healthy female. It is crucial to use iPSCs derived from healthy individuals as controls in genetic disease studies. Thus, we established a human iPSC cell line derived from healthy people. The iPSC cell line was generated in our lab from the peripheral blood mononuclear cells (PBMCs) of a 28-year-old girl. The generated hiPSC line is free of episomal vectors, has a normal karyotype, expresses pluripotency markers and can differentiate into three germ layers in vivo.

Network Pharmacology Combined with Molecular Docking and Experimental Verification Reveals the Bioactive Components and Potential Targets of Danlong Dingchuan Decoction against Asthma.

BACKGROUND: Danlong Dingchuan Decoction has a definite effect in the clinical treatment of asthma. This study aimed to explore the material and molecular biological basis of Danlong Dingchuan Decoction in treating asthma through network pharmacology combined with animal experiments. MATERIALS AND METHODS: First, the chemical constituents of Danlong Dingchuan Decoction were screened from the Traditional Chinese Medicine Systematic Pharmacology Analysis Platform (TCMSP) and the Traditional Chinese Medicine and Chemical Composition Database. Literature reports on asthma targets were obtained from the Online Mendelian Inheritance in Man (OMIM), Therapeutic Targets Database (TTD), and other databases. Then, the protein-protein interaction network was constructed according to the matching results of Danlong Dingchuan Decoction and asthma targets. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed by the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Finally, the interaction between the active compounds of Danlong Dingchuan Decoction and key targets was simulated using molecular docking. In animal experiments, ovalbumin was used to induce asthma in mice. After treating the mice by oral gavage administration of Danlong Dingchuan Decoction, the expression levels of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were detected in the lung tissue of the mice by enzyme-linked immunosorbent assay kit, whereas TLR4 mRNA expression was detected by quantitative reverse transcription-polymerase chain reaction. RESULTS: A total of 247 active compounds and 155 potential targets were obtained. Enrichment analysis showed that quercetin, xanthine, lysine, kaempferol, ß-sitosterol, and four other active compounds were the main components of Danlong Dingchuan Decoction; IL-6, TNF, CXCL8, VEGFA, MAPK3, IL-10, PTGS2, IL-1ß, IL-4, and TLR4 were the potential targets for therapy. KEGG analysis showed that the cAMP signaling pathway, cGMP-PKG signaling pathway, NF-κB signaling pathway, and PI3K-Akt signaling pathway might play an important role in treating asthma. Molecular docking analysis showed that quercetin combined well with TNF, CXCL8, and TLR4. Animal experiments showed that Danlong Dingchuan Decoction effectively reduced the expression levels of TNF-α, IL-4, TGF-ß1, IL-6, IL-8, and IL-1ß in the lung tissue of asthmatic mice and inhibited TLR4 mRNA expression. CONCLUSIONS: Danlong Dingchuan Decoction may act on key targets (such as IL-6, TNF, CXCL8, VEGFA, and MAPK3) with key active ingredients (such as quercetin, xanthine, lysine, kaempferol, and ß-sitosterol) to reduce the expression levels of IL-4, IL-6, IL-8, and other Th2 cytokines. This may be the mechanism by which Danlong Dingchuan Decoction reduces airway inflammation and treats asthma mediated by Th2 cytokines.

In vivo mRNA delivery to virus-specific T cells by light-induced ligand exchange of MHC class I antigen-presenting nanoparticles.

Simultaneous delivery of mRNA to multiple populations of antigen (Ag)-specific CD8+ T cells is challenging given the diversity of peptide epitopes and polymorphism of class I major histocompatibility complexes (MHCI). We developed Ag-presenting nanoparticles (APNs) for mRNA delivery using pMHCI molecules that were refolded with photocleavable peptides to allow rapid ligand exchange by UV light and site-specifically conjugated with a lipid tail for postinsertion into preformed mRNA lipid nanoparticles. Across different TCR transgenic mouse models (P14, OT-1, and Pmel), UV-exchanged APNs bound and transfected their cognate Ag-specific CD8+ T cells equivalent to APNs produced using conventionally refolded pMHCI molecules. In mice infected with PR8 influenza, multiplexed delivery of UV-exchanged APNs against three immunodominant epitopes led to ~50% transfection of a VHH mRNA reporter in cognate Ag-specific CD8+ T cells. Our data show that UV-mediated peptide exchange can be used to rapidly produce APNs for mRNA delivery to multiple populations of Ag-specific T cells in vivo.

Generation of a non-integrated induced pluripotent stem cell line (SMBCi009-A) from urine-derived cells of a Chinese Familial hypercholesterolemia patient.

Familial hypercholesterolemia (FH; OMIM: # 143890) is a common inherited autosomal dominant disease, characterized by high-level low-density lipoprotein cholesterol (LDL-C) in plasma. Elevated LDL-C levels is closely related with atherosclerotic plaques and premature cardiovascular disease if not treated in time. Here we generated an induced pluripotent stem cell (iPSC) line using urine cells (UCs) derived from an 8-year-old male FH patient who carrying two coding and pathogenic mutations of low-density lipoprotein receptor (LDLR) gene (exon12:c.C1747T and exon13: c. 1948 del G). This induced pluripotent stem cell line named SMBCi009-A can be used to understand more cellular details about FH.

Rhodium-Catalyzed Enantioselective and Desymmetrizative Pauson-Khand Reaction: Access to Tricyclo[6.2.1.04,11]undecenes.

Rhodium-catalyzed asymmetric desymmetrization Pauson-Khand reaction of C4-alkynyl-tethered cyclohexadienones has been developed as a novel strategy for access to fused 6-5-5 tricycles bearing three consecutive stereogenic centers. An array of chiral tricyclo[6.2.1.04,11]undecenes have been synthesized in high yields and enantioselectivities in a single step under mild conditions. This strategy employs readily accessible internal-olefin-containing 1,6-enynes, providing a potentially powerful tool for constructing chiral polycyclic scaffolds of complex molecules containing cyclopentenones and cyclohexenones.

Histone methylation in pancreatic cancer and its clinical implications.

Pancreatic cancer (PC) is an aggressive human cancer. Appropriate methods for the diagnosis and treatment of PC have not been found at the genetic level, thus making epigenetics a promising research path in studies of PC. Histone methylation is one of the most complicated types of epigenetic modifications and has proved crucial in the development of PC. Histone methylation is a reversible process regulated by readers, writers, and erasers. Some writers and erasers can be recognized as potential biomarkers and candidate therapeutic targets in PC because of their unusual expression in PC cells compared with normal pancreatic cells. Based on the impact that writers have on the development of PC, some inhibitors of writers have been developed. However, few inhibitors of erasers have been developed and put to clinical use. Meanwhile, there is not enough research on the reader domains. Therefore, the study of erasers and readers is still a promising area. This review focuses on the regulatory mechanism of histone methylation, and the diagnosis and chemotherapy of PC based on it. The future of epigenetic modification in PC research is also discussed.

Development of a human iPSC line (SMBCi004-A) from a patient with Gaucher disease.

A human induced pluripotent stem cell (iPSC) line was generated from the urine cells of a 8-year-old female with Gaucher disease with the homozygous changes c.1448 T>C in the GBA gene. Reprogramming factors OCT4, SOX2, KLF4, and miR-302-367 were delivered using a non-integrative plasmid. Our iPSCs showed complete pluripotency, normal genetic stability, and the ability to differentiate into three germ layers.

Noncovalent Interaction-Assisted Ferrocenyl Phosphine Ligands in Asymmetric Catalysis.

Noncovalent interactions are ubiquitous in nature and are responsible for the precision control in enzyme catalysis via the cooperation of multiple active sites. Inspired by this principle, noncovalent interaction-assisted transition metal catalysis has emerged recently as a powerful tool and has attracted intense interest. However, it is still highly desirable to develop efficient and operationally convenient ligands along this line with new structural motifs. Based on the specific nature of hydrogen bonding and ion pairing interactions, we developed a series of noncovalent interaction-assisted chiral ferrocenyl phosphine ligands, including Zhaophos, Wudaphos, and miscellaneous SPO-Wudaphos. Due to the assistance of noncovalent interactions, this catalytic mode is capable of achieving transition metal catalyzed asymmetric hydrogenation and other transformations with remarkable improvement of reactivity and selectivity. In some specific challenging cases, this probably represents one of the most productive methods. Moreover, these ligands are easily prepared, air stable, and highly tunable, meeting the requirements of industrial application.In this Account, we give a concise review of recent advances in asymmetric catalysis. By means of hydrogen bonding interactions, Rh- and Ir-Zhaophos complexes exhibited excellent activities and enantioselectivities in asymmetric hydrogenation of a wide range of substrates: C═C bonds of substituted conjugate alkenes with neutral hydrogen bond acceptors, including nitro groups, carbonyl groups (ketones, esters, amides, maleinimides, and anhydrides), ethers, and sulfones; C═N bonds of substituted iminium salts with chloride as an anionic hydrogen bond acceptor, including N-H imines and cyclic imines; N-heteroaromatic compounds with HCl as an additive, including unprotected quinolines, isoquinolines, and indoles; carbocation of substituted oxocarbenium ions. By means of ion pairing interactions, Rh-Wudaphos complexes enabled the catalytic asymmetric hydrogenation of α-substituted unsaturated carboxylic acids, carboxy-directed α,α-disubstituted terminal olefins, and sodium α-arylethenylsulfonates. Rh-SPO-Wudaphos utilized both hydrogen bonding and ion pairing interactions in asymmetric hydrogenation of α-substituted unsaturated carboxylic acids and phosphonic acids. In addition, Zhaophos has achieved highly selective intramolecular reductive amination and inter- and intramolecular asymmetric decarboxylative allylation. Investigations into mechanism implied that noncovalent interactions were involved in the catalytic cycle and played a critical role for both high reactivity and selectivity. Notably, a rare ionic hydrogenation pathway has been proposed in some cases. Furthermore, these catalytic systems have been used in the gram-scale synthesis of natural products and pharmaceuticals.

Asymmetric Hydrogenation of Cationic Intermediates for the Synthesis of Chiral N,O-Acetals.

For over half a century, transition-metal-catalyzed homogeneous hydrogenation has been mainly focused on neutral and readily prepared unsaturated substrates. Although the addition of molecular hydrogen to C=C, C=N, and C=O bonds represents a well-studied paradigm, the asymmetric hydrogenation of cationic species remains an underdeveloped area. In this study, we were seeking a breakthrough in asymmetric hydrogenation, with cationic intermediates as targets, and thereby anticipating applying this powerful tool to the construction of challenging chiral molecules. Under acidic conditions, both N- or O-acetylsalicylamides underwent cyclization to generate cationic intermediates, which were subsequently reduced by an iridium or rhodium hydride complex. The resulting N,O-acetals were synthesized with remarkably high enantioselectivity. This catalytic strategy exhibited high efficiency (turnover number of up to 4400) and high chemoselectivity. Mechanistic studies supported the hypothesis that a cationic intermediate was formed in situ and hydrogenated afterwards. A catalytic cycle has been proposed with hydride transfer from the iridium complex to the cationic sp2 carbon atom being the rate-determining step. A steric map of the catalyst has been created to illustrate the chiral environment, and a quantitative structure-selectivity relationship analysis showed how enantiomeric induction was achieved in this chemical transformation.

Anti-Proliferative Effect of Wogonin on Ovary Cancer Cells Involves Activation of Apoptosis and Cell Cycle Arrest.

BACKGROUND The present study was designed to investigate the effect of wogonin on Caov-3 and A2780 ovary cancer cell proliferation and the mechanisms involved. MATERIAL AND METHODS Cell viability changes and apoptosis induction by wogonin were assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenytetrazolium bromide) assay and fluorescence microscopy. Morphological examination of cells was performed using transmission electron microscopy. RESULTS Wogonin exhibited inhibitory effect on Caov-3 and A2780 cancer cell proliferation in a concentration-based manner. Caov-3 and A2780 cell proliferation was reduced to 18% and 21%, respectively on treatment with 200 µM concentration of wogonin. Treatment with wogonin significantly enhanced the percentage of A2780 cells showing apoptosis. The nuclear membrane degradation and condensation of chromatin material was evident in A2780 cells on treatment with wogonin. Treatment of A2780 cells with wogonin suppressed the migration potential significantly. The proportion of A2780 cells in G1/G0 phase was markedly raised on exposure to wogonin for 48 hours. CONCLUSIONS In summary, this study demonstrated that wogonin acts as an ovary cancer cell proliferation inhibiting agent through activation of apoptosis. Wogonin, therefore, can be investigated further for the development of ovary cancer treatment.

Chiral Phosphoric-Acid-Catalyzed Cascade Prins Cyclization.

Asymmetric Prins cyclization of in situ generated quinone methides and o-aminobenzaldehyde has been developed with chiral phosphoric acid as an efficient catalyst. This unconventional method provides a facile access to diverse functionalized trans-fused pyrano-/furo-tetrahydroquinoline derivatives in excellent yield and with excellent diastereo- and enantioselectivities (up to 99% yield and 99% ee). Mechanistic studies suggested that the three adjacent tertiary stereocenters were constructed through the sequential formation of C-O, C-C, and C-N bonds.

Azithromycin inhibits muscarinic 2 receptor-activated and voltage-activated Ca2+ permeant ion channels and Ca2+ sensitization, relaxing airway smooth muscle contraction.

Azithromycin (AZM) has been used for the treatment of asthma and chronic obstructive pulmonary disease (COPD); however, the effects and underlying mechanisms of AZM remain largely unknown. The effects of AZM on airway smooth muscles (ASMs) and the underlying mechanisms were studied using isometric muscle force measurements, the examination of lung slices, imaging, and patch-clamp techniques. AZM completely inhibited acetylcholine (ACH)-induced precontraction of ASMs in animals (mice, guinea pigs, and rabbits) and humans. Two other macrolide antibiotics, roxithromycin and Klaricid, displayed a decreased inhibitory activity, and the aminoglycoside antibiotics penicillin and streptomycin did not have an inhibitory effect. Precontractions were partially inhibited by nifedipine (selective inhibitor of L-type voltage-dependent Ca2+ channels (LVDCCs)), Pyr3 (selective inhibitor of TRPC3 and/or STIM/Orai channels, which are nonselective cation channels (NSCCs)), and Y-27632 (selective inhibitor of Rho-associated kinase (ROCK)). Moreover, LVDCC- and NSCC-mediated currents were inhibited by AZM, and the latter were suppressed by the muscarinic (M) 2 receptor inhibitor methoctramine. AZM inhibited LVDCC Ca2+ permeant ion channels, M2 receptors, and TRPC3 and/or STIM/Orai, which decreased cytosolic Ca2+ concentrations and led to muscle relaxation. This relaxation was also enhanced by the inhibition of Ca2+ sensitization. Therefore, AZM has potential as a novel and potent bronchodilator. The findings of this study improve the understanding of the effects of AZM on asthma and COPD.

Iridium-Catalyzed Asymmetric Hydrogenation of Tetrasubstituted α-Fluoro-ß-enamino Esters: Efficient Access to Chiral α-Fluoro-ß-amino Esters with Two Adjacent Tertiary Stereocenters.

An iridium-catalyzed highly efficient asymmetric hydrogenation of challenging tetrasubstituted α-fluoro-ß-enamino esters was successfully developed using bisphosphine-thiourea (ZhaoPhos) as the ligand, which prepared a series of chiral α-fluoro-ß-amino esters containing two adjacent tertiary stereocenters with high yields and excellent diastereoselectivities/enantioselectivities (73%-99% yields, >25:1 dr, 91%->99% ee, and turnover number (TON) values up to 8600), and no defluorinate byproduct was detected.

Palladium-Catalyzed N-Arylation of Sulfoximines with Aryl Sulfonates.

Palladium-catalyzed C-N bond coupling reaction between NH-sulfoximines and aryl halides (e.g., -Br, -I, and -Cl and pseudohalides -OTf and -ONf) was successfully achieved. Nevertheless, aryl tosylates/mesylates left much to be achieved. In this report, a general N-arylation of sulfoximines with aryl sulfonates is described. Using Pd(OAc)2/MeO-CM-phos complex, the N-aryl sulfoximine products can be obtained in good-to-excellent yields (up to 99%) with good common functional group compatibility. In addition to arene moieties, alkenyl tosylates are shown to be successful coupling partners.

Enantioselective Access to Chiral 2-Substituted 2,3-Dihydrobenzo[1,4]dioxane Derivatives through Rh-Catalyzed Asymmetric Hydrogenation.

Rh-catalyzed asymmetric hydrogenation of various benzo[ b][1,4]dioxine derivatives was successfully developed to prepare chiral 2-substituted 2,3-dihydrobenzo[1,4]dioxane derivatives using ZhaoPhos and N-methylation of ZhaoPhos ligands with high yields and excellent enantioselectivities (up to 99% yield, >99% enantiomeric excess (ee), turnover number (TON) = 24 000). Moreover, this asymmetric hydrogenation methodology, as the key step with up to 10 000 TON, was successfully applied to develop highly efficient synthetic routes for the construction of some important biologically active molecules, such as MKC-242, WB4101, BSF-190555, and ( R)-doxazosin·HCl.