TFA-Promoted Cascade Sulfonylation/Rearrangement/Cyclization of 1,5-Diynols and Sodium Sulfinates to Construct Sulfonylated Benzo[b]fluorenes.

A novel conversion of 1,5-diynols into sulfonylated benzo[b]fluorenes is reported by a TFA-promoted cascade cyclization with sodium sulfinates under mild conditions. This strategy provides an efficient and practical approach for accessing various sulfonated benzo[b]fluorenes in moderate to excellent yields under metal-free conditions. On the basis of the control experimental results and density functional theory calculations, a possible cascade transformation mechanism consisting of the dehydration of propargylic alcohols, sulfonylation, allenylation, and Schmittel-type cyclization is proposed. It is worth noting that TFA played an important role in this cascade cyclization, which promoted C-SO2R bond cleavage in a propargylic sulfone intermediate to form allenyl sulfones, followed by Schmittel-type cyclization to give the target product.

Photocatalytic Enantioselective Radical Cascade Multicomponent Minisci Reaction of ß-Carbolines Using Diazo Compounds as Radical Precursors.

Here, a photocatalytic asymmetric multicomponent cascade Minisci reaction of ß-carbolines with enamides and diazo compounds is reported, enabling an effective enantioselective radical C─H functionalization of ß-carbolines with high yields and enantioselectivity (up to 83% yield and 95% ee). This enantioselective multicomponent Minisci protocol exhibits step economy, high chemo-/enantio-selective control, and good functional group tolerance, allowing access to a variety of valuable chiral ß-carbolines. Notably, diazo compounds are suitable radical precursors in enantioselective cascade radical reactions. Moreover, the efficiency and practicality of this approach are demonstrated by the asymmetric synthesis of bioactive compounds and natural products.

Chiral Cpx Rhodium(III)-Catalyzed Enantioselective Aziridination of Unactivated Terminal Alkenes.

Chiral cyclopentadienyl-rhodium(III) Cpx Rh(III) catalysis has been demonstrated to be competent for catalyzing highly enantioselective aziridination of challenging unactivated terminal alkenes and nitrene sources. The chiral Cpx Rh(III) catalysis system exhibited outstanding catalytic performance and wide functional group tolerance, yielding synthetically important and highly valuable chiral aziridines with good to excellent yields and enantioselectivities (up to 99 % yield, 93 % ee). This protocol presents a novel and effective strategy for synthesizing enantioenriched aziridines from simple alkenes. Various transformations were performed on the aziridine products, illustrating the versatility and synthetic potential of this protocol for constructing highly functionalized compounds.

Electrochemical Arene Radical Cation Promoted Spirocyclization of Biaryl Ynones: Access to Alkoxylated Spiro[5,5]trienones.

Herein, a novel electrochemical arene radical cation promoted dearomative spirocyclization of biaryl ynones with alcohols is described, providing a conceptually novel transformation mode for producing diverse alkoxylated spiro[5,5]trienones. The catalyst- and chemical-oxidant-free spirocyclization protocol features broad substrate scope and high functional group tolerance. Mechanistic studies reveal that the generation of arene radical cation via anodic single-electron oxidation is crucial, with sequential 6-endo-dig cyclization, dissociation of hemiketal, anodic oxidation, and nucleophilic attack of alcohols.

Cascade Cyclization of 1,5-Diynols and (RO)2P(O)SH to Construct Benzo[b]fluorenyl S-Alkyl Phosphorothioates under Catalyst-Free Conditions.

An efficient and practical cascade cyclization of 1,5-diynols with (RO)2P(O)SH as the acid promoter and nucleophile under mild conditions was developed. A variety of highly substituted benzo[b]fluorenyl-containing S-alkyl phosphorothioates were successfully constructed in moderate to excellent yields. Furthermore, this protocol exhibited good functional group tolerance, a broad substrate scope, and potential practical applications, with water as the only byproduct. The reaction proceeded with allenyl thiophosphate as a key intermediate, followed by a Schmittel-type cyclization process to produce the target product.

Electrochemical 1,3-Alkyloxylimidation of Arylcyclopropane Radical Cations: Four-Component Access to Imide Derivatives.

Herein, a general electrochemical radical-cation-mediated four-component ring-opening 1,3-alkyloxylimidation of arylcyclopropanes, acetonitrile, carboxylic acids, and alcohols is described, providing a facile and sustainable approach to quickly construct structurally diverse imide derivatives from easily available raw materials in an operationally simple undivided cell. This metal-catalyst- and oxidant-free single-electron oxidation strategy offers a green alternative for the formation of highly reactive cyclopropane-derived radical cations, and this protocol features a broad functional group tolerance.

The Symptoms of Benign Prostatic Hyperplasia Patients with Stromal-Dominated Hyperplasia Nodules May Be Associated with Prostate Fibrosis.

Objective: The aim of the present study was to observe the effect of the stroma proportion in hyperplasia nodules on the clinical symptoms of benign prostatic hyperplasia (BPH) patients and to identify the different genes and pathways in prostatic hyperplasia nodules between patients with epithelial-dominated hyperplasia (EDH) and stromal-dominated hyperplasia (SDH) nodules. Methods: Sixty-seven BPH patient samples underwent transurethral resection of the prostate (TURP) were collected and retrospectively analyzed. The differences in clinical parameters between the EDH and SDH groups were investigated. Collagen fiber percentage was assessed, and the correlation with clinical parameters was evaluated. mRNA sequencing in hyperplasia nodules of 8 BPH patients was performed, and differentially expressed genes (DEGs) between the EDH and SDH groups were screened. These DEGs were analyzed using GO, KEGG and PPI analysis. Results: The results showed the IPSS was significantly higher in the SDH group than in the EDH group (p < 0.01). The collagen fiber percentage of BPH nodules was higher in the SDH group than in the EDH group (p < 0.05), and the collagen fiber percentage was positively correlated with the IPSS (r = 0.4058, p = 0.0007). A total of 172 DEGs were obtained, including 63 up-regulated genes and 109 down-regulated genes. GO and KEGG pathway enrichment analyses showed DEGs were mainly enriched in extracellular matrix structural constituents. The top 10 hub genes were associated to the components of extracellular matrix and fibrosis. Conclusion: These results suggested that the symptoms of BPH patients with SDH nodules may be associated with prostate fibrosis and fibrosis may be a significant contributing factor in BPH/LUTS patients with SDH nodules.

Electrochemically enabled decyanative C(sp3)-H oxygenation of N-cyanomethylamines to formamides.

Selective oxygenation of C(sp3)-H bonds adjacent to nitrogen atoms is a highly attractive strategy for synthesizing various formamide derivatives while preserving the substrate skeletons. Herein, an environmentally benign electrochemically enabled decyanative C(sp3)-H oxygenation of N-cyanomethylamines using H2O as a carbonyl oxygen atom source is described, leading to the synthesis of a large class of formamides in good to excellent yields with a broad substrate scope under metal- and oxidant-free conditions. This electrochemical technology highlights the facile incorporation of N-formyl into some important bioactive molecules.

Alterations in the balance of sex hormones may affect rat prostatic inflammation and fibrosis, and osteopontin might be involved in this process.

OBJECTIVE: This study aimed to investigate the effects of sex hormone imbalance on rat prostatic inflammation and fibrosis and identify the key molecules involved. METHODS: Castrated Sprague-Dawley (SD) rats were treated with a constant dose of oestradiol (E2) and different doses of dihydrotestosterone (DHT) to achieve different oestrogen/androgen ratios. After 8 weeks, serum E2 and DHT concentrations, relative seminal vesicle weights, histopathological changes and inflammation were measured, collagen fiber content and oestrogen receptor (ER) and androgen receptor (AR) expression were detected, mRNA sequencing and bioinformatics analysis were performed to identify differentially expressed genes (DEGs). RESULTS: The severity of inflammation in the rat dorsolateral prostate (DLP) was higher, collagen fibre content and ER expression in the rat DLP and prostatic urethra were increased and AR expression in the rat DLP was decreased in the 1:1 E2/DHT-treated group than that in the 1:10 E2/DHT-treated group. RNA-seq analysis identified 487 DEGs, and striking increases in the expression of mRNAs encoding collagen, collagen synthesis and degradation enzymes, growth factors and binding proteins, cytokines and chemokines, and cell-surface molecules were confirmed in the 1:1 E2/DHT-treated group compared to the 1:10 E2/DHT-treated group. mRNA expression of secreted phosphoprotein 1 (Spp1) and protein expression of osteopontin (OPN, encoded by Spp1) were increased in the 1:1 E2/DHT-treated group compared to the 1:10 E2/DHT-treated group, and Spp1 expression correlated positively with Mmp7, Cxcl6 and Igfn1 expression. CONCLUSIONS: The imbalance in the oestrogen/androgen ratio may affect rat prostatic inflammation and fibrosis, and OPN might be involved in this process.

Deferoxamine in intracerebral hemorrhage: Systematic review and meta-analysis.

BACKGROUND: Intracerebral hemorrhage (ICH) is a stroke with a high morbidity and mortality rate. Deferoxamine (DFX) is thought to be effective in treating Intracerebral Hemorrhage. In our study, we performed a meta-analysis to evaluate the treatment effects of DFX. METHODS: We systematically searched PubMed, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and Chinese Biomedical Literature Database in Jan 2022 for studies on DFX for ICH patients. Outcome measures included relative hematoma volume, relative edema volume, good neurological functional outcome and adverse events. Odds risk (OR) and weighted mean difference (WMD) were used to evaluate clinical outcomes. RESULTS: After searching 636 articles, 4 RCTs, 2 NRCTs, and 1cohort study were included. We found that DFX was effective in hematoma absorption on day 7 after onset, but the difference was not significant on day 14. DFX could suppress edema expansion on days 3, 7, and 14 after onset. DFX did not contribute to better outcomes after 3 and 6 months when used the modified Rankin Scale and the Glasgow Outcome Scale to evaluate neurological prognosis. The pooled results showed no statistically significant difference in Serious adverse events between the experimental and control groups. CONCLUSIONS: DFX could limit edema expansion on days 3, 7, and 14 after commencement and facilitate hematoma absorption at week 1 without significantly increasing the risk of adverse events, but it did not improve neurological prognosis.

Photocatalytic enantioselective Minisci reaction of ß-carbolines and application to natural product synthesis.

A highly efficient enantioselective direct C-H functionalization of ß-carbolines via a Minisci-type radical process under a photo-redox and chiral phosphoric acid cooperative catalytic system has been disclosed. Through this protocol, a wide range of C1 aminoalkylated ß-carbolines were constructed directly with high levels of enantioselectivities from readily available ß-carbolines and alanine-derived redox-active esters. This transformation allows straightforward access to highly valuable enantioenriched ß-carbolines, which are an intriguing structural motif in valuable natural products and synthetic bio-active compounds. This protocol has been utilized as a highly efficient synthetic strategy for the concise asymmetric total synthesis of marine alkaloids eudistomin X, (+)-eudistomidin B and (+)-eudistomidin I.

Design, synthesis, and herbicidal activity of indole-3-carboxylic acid derivatives as potential transport inhibitor response 1 antagonists.

Auxins as an important class of phytohormones play essential roles in plant life cycle; therefore, developing compounds with auxin-like properties for plant growth regulation and weed control applications is of great significance. Herein, we reported the design, synthesis, and herbicidal activity evaluation of a series of novel indole-3-carboxylic acid derivatives as auxin receptor protein TIR1 antagonists. Petri dish herbicidal activity assay demonstrated that most of the as-synthesized target compounds exhibited good-to-excellent inhibition effects (60-97% inhibitory rates) on roots and shoots of both dicotyledonous rape (B. napus) and monocotyledonous barnyard grass (E. crus-galli). The inhibition rates of compounds 10d and 10h reached up to 96% and 95% for the root of rape (B. napus) at 100 mg/L, and they also maintained 92% and 93% inhibition rates even if at 10 mg/L, respectively. Molecular docking revealed that the interactions between these synthesized target compounds and TIR1 protein include tight π-π stacking, hydrogen bond, and hydrophobic interactions. This work expands the range of auxin chemistry for the development of new auxin mimic herbicides.

Electro-/photocatalytic alkene-derived radical cation chemistry: recent advances in synthetic applications.

Alkene-derived radical cations are versatile reactive intermediates and have been widely applied in the construction of complex functionalized molecules and cyclic systems for chemical synthesis. Therefore, the synthetic application of these alkene-derived radical cations represents a powerful and green tool that can be used to achieve the functionalization of alkenes partially because the necessity of stoichiometric external chemical oxidants and/or hazardous reaction conditions is eliminated. This review summarizes the recent advances in the synthetic applications of the electro-/photochemical alkene-derived radical cations, emphasizing the key single-electron oxidation steps of the alkenes, the scope and limitations of the substrates, and the related reaction mechanisms. Using electrocatalysis and/or photocatalysis, single electron transfer (SET) oxidation of the CC bonds in the alkenes occurs, generating the alkene-derived radical cations, which sequentially enables the functionalization of translocated radical cations to occur in two ways: the first involves direct reaction with a nucleophile/radical or two molecules of nucleophiles to realize hydrofunctionalization, difunctionalization and cyclization; and the second involves the transformation of the alkene-derived radical cations into carbon-centered radicals using a base followed by radical coupling or oxidative nucleophilic coupling.

Electrochemical 1,2-Diarylation of Alkenes Enabled by Direct Dual C-H Functionalizations of Electron-Rich Aromatic Hydrocarbons.

A cobalt-promoted electrochemical 1,2-diarylation of alkenes with electron-rich aromatic hydrocarbons via direct dual C-H functionalizations is described, which employs a radical relay strategy to produce polyaryl-functionalized alkanes. Simply by using graphite rod cathode instead of platinum plate cathode, chemoselectivity of this radical relay strategy is shifted to the dehydrogenative [2+2+2] cycloaddition via 1,2-diarylation, annulation, and dehydrogenation cascades leading to complex 11,12-dihydroindolo[2,3-a]carbazoles. Mechanistical studies indicate that a key step for the radical relay processes is transformations of the aromatic hydrocarbons to the aryl sp2 -hybridized carbon-centered radicals via deprotonation of the corresponding aryl radical cation intermediates with bases.

Chemical Composition of Essential Oil from Flower of 'Shanzhizi' (Gardenia jasminoides Ellis) and Involvement of Serotonergic System in Its Anxiolytic Effect.

Gardenia jasminoides Ellis is a famous fragrant flower in China. Previous pharmacological research mainly focuses on its fruit. In this study, the essential oil of the flower of 'Shanzhizi', which was a major variety for traditional Chinese medicine use, was extracted by hydro distillation and analyzed by GC-MS. Mouse anxiety models included open field, elevated plus maze (EPM), and light and dark box (LDB), which were used to evaluate its anxiolytic effect via inhalation. The involvement of monoamine system was studied by pretreatment with neurotransmitter receptor antagonists WAY100635, flumazenil and sulpiride. The monoamine neurotransmitters contents in the prefrontal cortex (PFC) and hippocampus after aroma inhalation were also analyzed. The results showed that inhalation of G. jasminoides essential oil could significantly elevated the time and entries into open arms in EPM tests and the time explored in the light chamber in LDB tests with no sedative effect. WAY100635 and sulpiride, but not flumazenil, blocked its anxiolytic effect. Inhalation of G. jasminoides essential oil significantly down-regulated the 5-HIAA/5-HT in the PFC and reduced the 5-HIAA content in hippocampus compared to the control treatment. In conclusion, inhalation of gardenia essential oil showed an anxiolytic effect in mice. Monoamine, especially the serotonergic system, was involved in its anxiolytic effect.

Electrochemical Alkoxyhalogenation of Alkenes with Organohalides as the Halide Sources via Dehalogenation.

A general, ideal atom utilization electrochemical technology to enable alkene alkoxyhalogenation and organohalide dehalogenation in one pot is presented. This technology is highlighted by convergent strategy integrating several reactions, such as alkene alkoxyhalogenation, organohalide dehalogenation, and dehalogenation deuteration. Experimental data suggest that alkenes have the lowest oxidation potential, which lead to anodic conversion of the C═C bond to the radical cation intermediates, and cathodic transformations of organohalides, including alkyl and aryl halides, as the nucleophilic halogen sources.

Radical-mediated oxidative annulations of 1,n-enynes involving C-H functionalization.

The 1,n-enyne annulation reaction has emerged as one of the most powerful and straightforward tools to build carbo- and hetero-cyclic frameworks that are found in numerous natural products, pharmaceuticals and functional materials. Although the 1,n-enyne annulation methods have been well documented to date, there is a tremendous challenge with current methodologies for simultaneously incorporating external functional groups into the resulting cyclic systems. Recent advances in the radical-mediated oxidative 1,n-enyne annulation strategy involving C-H functionalization have been proven to be an ideal alternative to overcome these disadvantages. Such radical-mediated oxidative 1,n-enyne annulation can be accomplished by two different C-H functionalization modes: One proceeds through generation of the carbon-centered radicals from C-H bond direct oxidative cleavage and their subsequent addition across the C[double bond, length as m-dash]C bond or C[triple bond, length as m-dash]C bond enabling the 1,n-enyne annulation; the other employs the C-H bonds as the radical acceptors to terminate the initial oxidative radical-triggered annulation of 1,n-enyne. In addition, during many annulation processes the inherent C-H bonds of 1,n-enynes were functionalized. Here, we summarize recent progress in radical-mediated oxidative annulations of 1,n-enynes involving two different conceptual C-H functionalization strategies and the inherent C-H functionalization with an emphasis on the scope, limitations and mechanisms of these different reactions.

Electrochemical dehydrogenative cross-coupling of two anilines: facile synthesis of unsymmetrical biaryls.

A new, general ortho/para-selective anodic dehydrogenative cross-coupling of two aryl amines, naphthalen-2-amine derivatives and anilines, is described. This electrochemical protocol assembles a wide range of unsymmetrical biaryls in good to excellent yields under mild, additional-metal-catalyst-free, oxidant-free conditions with excellent selectivity, broad substrate scope, and wide functional group tolerance. This electrochemical technology is highlighted with facile incorporation of important pharmacophores into the resulting biaryls, and is applicable to the homocoupling of anilines for producing symmetrical biaryls.

Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) promotes the EMT of serous ovarian cancer by activating the hexosamine biosynthetic pathway to increase the nuclear location of ß-catenin.

The hexosamine biosynthetic pathway (HBP), a branch of glucose metabolism, provides a substrate for glycosylation modification, which has a wide-ranging effect on cellular functions. Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) has been reported to regulate the HBP as the first and rate-limiting enzyme. Given the inverse association between GFPT2 expression and survival of patients with serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database, we attempted to investigate the role of GFPT2 and its related mechanisms in SOC. The results showed that GFPT2 was over-expressed in SOC tissues, and positive correlations with advanced stage (FIGO III/IV), suboptimal removal rate and poor survival were observed in 90 SOC patients. Cell migration and invasion were also inhibited in GFPT2 knockdown SKOV3 and HEY cells. The levels of O-linked ß-N-acetylglucosamine (O-GlcNAc) and intranuclear ß-catenin were evaluated and the observed increase in O-GlcNAcylation induced by GFPT2 may contribute to epithelial-mesenchymal transition (EMT). These data provide novel insights into the function of GFPT2 and O-GlcNAcylation in the EMT and thus the invasiveness SOC.

Silver-catalyzed oxidative 1,2-alkyletherification of unactivated alkenes with α-bromoalkyl carbonyls: facile access to highly substituted 2,3-dihydrofurans.

A new, general silver-catalyzed oxidative 1,2-alkyletherification of unactivated olefinic ketones with primary, secondary and tertiary α-bromoalkyl carbonyls promoted by tert-butyl hydroperoxide (TBHP) and Et3N has been developed. Through the cooperative action of Ag2O, TBHP and Et3N, the reaction enables the construction of highly valuable quaternary-carbon-possessing 2,3-dihydrofuran frameworks using a concomitant intramolecular annulation strategy.