Hypervalent Iodine Mediated Synthesis of Sulfinamidines from Sulfenamides.

In this study, we present a novel, efficient method for the oxidative amination of sulfenamides using diacetoxyiodobenzene (PhI(OAc)2) and amines under basic conditions. This innovative technique streamlines the synthesis of sulfinamidines under mild, metal-free conditions, achieving outstanding yields of up to 99%. Furthermore, we propose possible pathways that elucidate the observed molecular sequence of events in this reaction. This cutting-edge approach not only advances the synthesis of valuable sulfinamidine compounds but also expands the synthetic toolbox available to chemists, paving the way for future discoveries in organic synthesis and potential applications in medicinal chemistry.

Copper-Catalyzed Aerobic S-Amination of Sulfenamides for the Synthesis of Sulfinamidines.

Herein, we present a copper-catalyzed oxidative amination of sulfenamides for the synthesis of sulfinamidines. By the employment of air as the terminal oxidant, a diverse array of secondary and primary amines can be efficiently transformed into their corresponding products. This method is well-suited for last-stage functionalization, and the underlying mechanism has been investigated. The transformation is characterized by exceptional chemoselectivity, mild conditions, facile operation, and broad substrate compatibility, which have significant implications for the fields of pharmaceuticals and organic synthesis.

A highly efficient method to access unprotected C-3 bifunctional quaternary 3-allyl-3-(amino)oxindoles.

A highly efficient Rh(II) catalyzed non-radical protocol to access NH-free C-3 bifunctional oxindoles, which possess 3-allyl and 3-amino simultaneously, was first achieved by employing an intermolecular [2,3]-sigmatropic rearrangement reaction between diazooxindoles and tertiary allylic amines. Utilizing readily available allylamines as the nitrogen and allyl source concurrently, a wide range of bio-active 3-allyl-3-(amino)oxindoles were obtained in excellent yields under very mild reaction conditions; meanwhile, the TON can be up to 90 000. Our study addresses a gap in the literature by investigating intermolecular rearrangements of ammonium ylides with diazoamides, which have been relatively understudied.

Rh(II)-catalyzed Doyle-Kirmse reaction: access to unprotected 3-allyl/3-allenyl-3-(thio)oxindoles.

The construction of the 3-allyl/3-allenyl-3-(thio)oxindole core remains a challenge in organic synthesis. Herein, we report a novel Rh2(esp)2 catalytic Doyle-Kirmse reaction to furnish the oxindole core, bearing unbiased NH as well as a quaternary stereogenic center at the 3-position, in good to excellent yields under mild conditions. These reactions are concise, practical, atom-economic, and highly efficient, and feature a TON of up to 3700. Moreover, a non-radical pathway was observed in this approach.

Loss of core fucosylation in both ST6GAL1 and its substrate enhances glycoprotein sialylation in mice.

Fucosyltransferase 8 (FUT8) and ß-galactoside α-2,6-sialyltransferase 1 (ST6GAL1) are glycosyltransferases that catalyze α1,6-fucosylation and α2,6-sialylation, respectively, in the mammalian N-glycosylation pathway. They are aberrantly expressed in various human diseases. FUT8 is non-glycosylated but is responsible for the fucosylation of ST6GAL1. However, the mechanism for the interaction between these two enzymes is unknown. In this study, we show that serum levels of α2,6-sialylated N-glycans are increased in Fut8-/- mice, whereas the mRNA and protein levels of ST6GAL1 are unchanged in mouse live tissues. The level of α2,6-sialylation on IgG was also enhanced in Fut8-/- mice along with ST6GAL1 catalytic activity increase in both serum and liver. Moreover, it was observed that ST6GAL1 prefers non-fucosylated substrates. Interestingly, increased core fucosylation accompanied by a reduction in α2,6-sialylation, was detected in rheumatoid arthritis patient serum. These findings provide new insight into the interactions between FUT8 and ST6GAL1.

Access to Substituted Thiophenes through Xanthate-Mediated Vinyl C(sp2)-Br Bond Cleavage and Heterocyclization of Bromoenynes.

An environmentally sustainable strategy for the chemoselective heterocyclization of bromoenynes through a transition-metal-free sulfuration/cyclization process is reported. Using inexpensive and safe EtOCS2K as a thiol surrogate and tetrabutylphosphonium bromide and H2O as a mixed solvent, the reaction provided a range of substituted thiophenes in moderate to good yields. In addition, 2,3,4,5-tetrasubstituted thiophenes were able to be prepared under mild reaction conditions by electrophilic heterocyclization with NH4I and EtOCS2K in good yields.

Redox-Neutral Strategy for Sulfilimines Synthesis via S-Arylation of Sulfenamides.

In this investigation, an unprecedented transition-metal-free and redox-neutral synthesis of sulfilimines was realized through the S-arylation of readily obtainable sulfenamides employing diaryliodonium salts. The pivotal step encompassed the resonance between bivalent nitrogen-centered anions, engendered postdeprotonation of sulfenamides under alkaline conditions, and sulfinimidoyl anions. The experimental outcomes demonstrate that sulfinimidoyl anionic species function as efficacious nucleophilic reagents, affording sulfilimines with notable to exceptional yields and superlative chemoselectivity, all executed within a transition-metal-free protocol and under exceptionally mild conditions.

Redox-Neutral Synthesis of Sulfilimines through the S-Alkylation of Sulfenamides.

In this work, we developed a metal-free and redox-neutral strategy for the selective S-alkylation of sulfenamides under basic conditions to yield sulfilimines. The key step involves the resonance between bivalent nitrogen-centered anions, generated after deprotonation of sulfenamides under alkaline conditions, and sulfinimidoyl anions. Our sustainable and efficient approach employs sulfur-selective alkylation of readily accessible sulfenamides and commercially available halogenated hydrocarbons, resulting in the successful synthesis of 60 sulfilimines in high yields (36-99%) and short reaction times.

Structurally diverse sulphur-containing amides from Glycosmis craibii with their potential antiproliferative activities.

Fourteen new sulphur-containing amides, glycocramides A-N (1-14), as well as nine known analogues (15-23) were isolated and characterized from Glycosmis craibii Tanaka. The chemical structures of new sulphur-containing amides 1-14 were ambiguously elucidated by extensive spectroscopic methods, while the known compounds 15-23 were identified by the comparison of their experimental spectral data with those described data in the literatures. The antiproliferative effects of all isolated sulphur-containing amides were evaluated in vitro. As a result, part of sulphur-containing amides showed remarkable inhibitory effects against MGC-803 cell line with IC50 values ranging from 13.12 ± 0.10 to 20.03 ± 0.13 µM. These research results suggest that the sulphur-containing amides are potentially to be developed as a new natural anti-tumor drugs.

Hypervalent Iodine-Mediated Synthesis of Sulfinimidate Esters from Sulfenamides.

In this study, we present a novel and efficient approach for the oxidative esterification of sulfenamides using phenyliodonium diacetate, enabling the synthesis of sulfinimidate esters and sulfilimines under mild and metal-free conditions, with yields reaching up to 99%. The protocol is readily scalable and compatible with a diverse range of substrates and functional groups, and we demonstrate its potential for late-stage functionalization of pharmacologically relevant molecules. Furthermore, we propose a plausible reaction mechanism to account for the observed sequence of events.

Changes of Serum Zinc-α2-Glycoprotein Level and Analysis of Its Related Factors in Gestational Diabetes Mellitus.

Previous studies have discovered that zinc-α2-glycoprotein (ZAG) is related to insulin resistance and lipid metabolism. The aim of the study is to explore the change of serum ZAG and its related factors in gestational diabetes mellitus (GDM). Eighty newly diagnosed GDM patients were enrolled in the case group, and 80 normal pregnant women were selected as the control group. The differences of baseline data between the two groups were compared, and the change of serum ZAG level and its relationship with related indexes was analyzed. Compared to the control group, the level of serum ZAG in GDM women decreased (P < 0.001). What is more, the serum ZAG level of overweight and normal subjects in two groups was also found to have statistical differences. The Pearson correlation (or Spearman correlation) analysis showed that serum ZAG level was negatively correlated with FPG, FINS, HOMA-IR, and TG (all P < 0.05) and positively correlated with HDL (P < 0.05). Multiple linear regression showed that HDL and HOMA-IR were independent factors of serum ZAG (P < 0.05). The level of serum ZAG in patients with gestational diabetes mellitus decreased, and HDL and HOMA-IR are the influencing factors in the case group.

Access to 4-substituted isothiazoles through three-component cascade annulation and their application in C-H activation.

The use of potassium ethyl xanthate (EtOCS2k) as a sulfur atom donor enabled the transition-metal-free [3 + 1 + 1] cascade annulation of isopropene derivatives with NH4I in DMSO/H2O, affording various 4-substituted isothiazoles in moderate to good yields with good functional group compatibility. Furthermore, Pd and Ag-catalyzed C5-H-selective direct oxidation dimerization of 4-substituted isothiazoles afforded 5,5'-bisisothiazoles. This series of reactions included the formation of new C-S, C-N, N-S, and C-C bonds via cascade addition, annulation, and direct C-H activation under mild conditions.

A fixation method for the optimisation of western blotting.

Western blotting is the most extensively used technique for the identification and characterisation of proteins and their expression levels. One of the major issues with this technique is the loss of proteins from the blotted membrane during the incubation and washing steps, which affects its sensitivity and reproducibility. Here, we have optimised the fixation conditions for immunoblotting and lectin blotting on electroblotted polyvinylidene difluoride and nitrocellulose membranes, using a combination of organic solvents and heating. Loss of proteins from polyvinylidene difluoride membranes was greatly reduced using this approach, the intensity of lectin blotting and immunoblotting was shown to increase 2.8- to 15-fold and 1.8- to 16-fold, respectively, compared with that samples without treated. Using the optimised method, cystic fibrosis transmembrane regulator and hypoxia-inducible factor 1, two difficult-to-analyse proteins with important physiological and pathological roles, were effectively detected. Additionally, it may help the identification of novel diagnostic markers for prostate cancer.

Inexpensive Weight-Reducing Aid (L-Carnitine) as An Efficient Catalyst for Synthesis of Benzimidazoles.

AIM AND OBJECTIVE: The benzimidazole derivatives have been obtained via weightreducing aid (L-Carnitine) as a cheap catalyst. A wide range of aromatic aldehydes easily undergo condensations with substituted o-phenylendiamine under mild condition to afford the target molecular in excellent yields. MATERIALS AND METHODS: Melting points were measured on an Electrothemal X6 microscopy digital melting point apparatus. 1H NMR and 13C NMR spectra were recorded in DMSO-d6 on a Bruker AVANCE 400 (400 MHz) instrument with the TMS at d 0.00 ppm as an internal standard. C, H and N analysis were performed by a Perkin-Elmer 2400 CHN elemental analyzer. Chemicals used were of commercial grade without further purification. An equimloar (1.0 mmol) mixture of o-phenylenediamine 1, aromatic aldehyde 2, and L-Carnitine (10 mol%) was vigorously stirred at 60°C in EtOH (3 mL) for the specific time indicated by TLC (petroleum: ethyl acetate ether = 4:1). After completion of the reaction, the mixture was quenched by adding H2O (20 mL), extracted with EtOAc (3 x 10 mL), and the combined extracts were dried by anhydrous MgSO4. The filtrate was evaporated and the corresponding benzimidazole was obtained as the only product. The products 3a-3r were obtained in 82-95% yields. The structures of the products 3 were identified by their IR, 1H NMR, 13C NMR and elemental analysis spectra. RESULTS: The products were obtained in 82-95% yields in 30-80 min. The method has several advantages such as simple, clean and environmentally process, excellent yield and avoiding use of inconvenient preparation of catalyst. Meanwhile, the catalyst L-Carnitine is a kind of weightreducing aid, which might be applied to broad green catalyzed system. CONCLUSION: A facile synthesis of benzimidazoles comprising the reaction of various aldehydes with substituted o-phenylendiamine in good to excellent yield is provided using L-Carnitine as an efficient catalyst. The protocol overcomes the earlier disadvantages like harsh reaction conditions, tedious work-up, expensive process, wastes generation and the use of metallic oxide, which might be applied to the synthesis of benzimidazoles pharmaceticals in order to meet friendly environmental demands.

Inhibition of store-operated Ca2+ entry counteracts the apoptosis of nasopharyngeal carcinoma cells induced by sodium butyrate.

Sodium butyrate (NaBu), a histone deacetylase inhibitor, has demonstrated anti-tumor effects in several cancers, and is a promising candidate chemotherapeutic agent. However, its roles in nasopharyngeal carcinoma (NPC), an endemic malignant disease in Southern China and Southeast Asia, has rarely been studied. In the present study, MTT assay, colony formation assay, flow cytometry analysis and western blotting were performed to explore the influence of NaBu on NPC cells and its underlying mechanism. NaBu induced morphological changes and inhibited proliferation in 5-8F and 6-10B cells. MTT assay revealed that NaBu was cytotoxic to 5-8F and 6-10B cells in a dose- and time-dependent manner. Furthermore, flow cytometry analysis revealed that NaBu induced obvious cell apoptosis in 5-8F and 6-10B cells due to the activation of the mitochondrial apoptosis axis. In addition, flow cytometry analysis and western blotting demonstrated that NaBu could enhance the Ca2+ influx by promoting store-operated Ca2+ entry (SOCE) in 5-8F and 6-10B cells. Inhibition of SOCE by specific inhibitors or downregulated expression of calcium release-activated calcium channel protein 1 and stromal interaction molecule 1 could counteract the apoptosis of NPC cells induced by NaBu. Thus, the current study revealed that enhanced SOCE and activated mitochondrial apoptosis axis may account for the mechanisms of cytotoxicity of NaBu in NPC cells, and that NaBu serves as a promising chemotherapeutic agent in NPC therapy.

DLC-1 induces mitochondrial apoptosis and epithelial mesenchymal transition arrest in nasopharyngeal carcinoma by targeting EGFR/Akt/NF-κB pathway.

Loss of deleted in liver cancer-1 (DLC-1) can induce apoptosis and inhibit the mobility, migration and metastasis in several cancers. Previously, we revealed that ectopic expression of DLC-1 can suppress proliferation, mobility, migration and tumorigenesis in nasopharyngeal carcinoma (NPC). However, the molecular mechanisms accounting for the roles of DLC-1 in NPC are still obscure. In the present work, we attempted to study and uncover the mechanisms underlying the functions of DLC-1 in NPC. The apoptosis of 5-8F-DLC-1 cells, established previously, was analyzed by mitochondrial membrane potentials assay and flow cytometer analysis. And the antibodies involving pathways such as mitochondrial-associated apoptosis, epithelial mesenchymal transition and metastasis were applied to detect and compare the expression level of targeted proteins. The obvious apoptosis of 5-8F-DLC-1 cells was observed reflected by mitochondrial depolarization and lower ratio in cell viability. Subsequently, the activation of mitochondrial apoptosis was verified by the increased expressions of Bax, Apaf1, cleave-caspases and cleave-PARP, etc, and the decreased expressions of Bcl-2, Bcl-xL, Mcl-1, Survivin, etc, in 5-8F-DLC-1 cells. Then, the inhibited epithelial mesenchymal transition of 5-8F-DLC-1 cells was validated by upregulated expression of E-cadherin and downregulated expression of N-cadherin, Snail, Vimentin. Subsequently, downregulated expressions of proteins such as FAK, RhoA, ROCK1 and cdc25 related to cell adhesion and cytoskeleton organization were also observed. And expressions of MMPs were inhibited in 5-8F-DLC-1 cells. At last, the inhibited activity of EGFR/Akt/NF-κB axis was revealed by the decreased expressions of phosho-EGFR, phosho-Akt, phosho-p38MAPK, phosho-IKKα and phosho-p65. Here, we systematically explored the mechanisms underlying the negative roles of DLC-1 in NPC cells. For the first time, we confirmed that the ectopic expression DLC-1 can induce mitochondrial apoptosis, inhibit EMT and related processes by targeting the EGFR/Akt/NF-κB pathway, which, beyond all doubt, offered beneficial guidelines for other studies and laid a good foundation for its clinical applications ultimately.