A mild protocol for efficient preparation of functional molecules containing triazole.

The construction of a class of novel triazole molecules containing sulfonyl fluoride functionalities was achieved through Cu-catalyzed click chemistry in good to excellent yields. The sulfonyl fluoride moieties were cleaved completely under base conditions to produce N-unsubstituted triazoles quantitatively, which provides a strategy to combine SuFEx click chemistry with Cu-catalyzed click chemistry ingeniously.

Design, synthesis and biological evaluation of novel arylpropionic esters for the treatment of acute kidney injury.

Acute kidney injury (AKI) is associated with a strong inflammatory response, and inhibiting the response effectively prevents or ameliorates AKI. A series of novel arylpropionic esters were designed, synthesized and evaluated their biological activity in LPS-stimulated RAW264.7 cells. Novel arylpropionic esters bearing multi-functional groups showed significant anti-inflammatory activity, in which, compound 13b exhibited the most potent activity through dose-dependent inhibiting the production of nitric oxide (NO, IC50 = 3.52 µM), TNF-α and IL-6 (84.1% and 33.6%, respectively), as well as suppressing the expression of iNOS, COX-2 and TLR4 proteins. In C57BL/6 mice with cisplatin-induced AKI, compound 13b improved kidney function, inhibited inflammatory development, and reduced pathological damage of kidney tissues. In brief, this arylpropionic ester scaffold may be developed as anti-inflammatory agents.

Clickable Transformation of Nitriles (RCN) to Oxazolyl Sulfonyl Fluoride Warheads.

The protocol for simple, efficient, and mild synthesis of oxazolyl sulfonyl fluorides was developed through Rh2(OAc)4-catalyzed annulation of methyl-2-diazo-2-(fluorosulfonyl)acetate (MDF) or its ethyl ester derivative with nitriles. This practical method provides a general and direct route to a unique class of highly functionalized oxazolyl-decorated sulfonyl fluoride warheads with great potential in medicinal chemistry, chemical biology, and drug discovery.

Protocol for Stereoselective Construction of Highly Functionalized Dienyl Sulfonyl Fluoride Warheads.

A pyrrolidine-mediated Knoevenagel-type reaction for highly stereoselective construction of novel α-halo-1,3-dienylsulfonyl fluorides was achieved in up to 100% Z-selectivity and high yields at room temperature from condensation of the readily available aldehydes and halomethanesulfonyl fluorides. This protocol provided a class of unique α-halo-1,3-dienylsulfonyl fluorides with wide scope and excellent functional group compatibility. The α-halo-1,3-dienylsulfonyl fluorides were used as versatile building blocks in sulfur fluoride exchange click chemistry, Suzuki reaction, and Sonogashira reaction for the assembly of highly functionalized dienyl sulfonyl fluoride derivatives to be applied as covalent warheads for the discovery of new drugs.

Light-induced [2 + 2] cycloadditions for the construction of cyclobutane-fused pyridinyl sulfonyl fluorides.

Cyclobutanes are an important class of motifs present in a wide range of natural products and other biologically significant molecules. A photocatalytic [2 + 2] cycloaddition between pyridones or isoquinolones and ethenesulfonyl fluoride was achieved, providing a portal to a class of unique cyclobutane-fused pyridinyl sulfonyl fluorides with quaternary rigid rings (30 examples). Further applications of these novel sulfonyl fluoride molecules in SuFEx click chemistry were also accomplished, providing the corresponding sulfonates and sulphonamides with reasonable yields.

Installation of -SO2F groups onto primary amides.

A protocol of SO2F2-mediated installation of sulfonyl fluoride onto primary amides has been developed providing a new portal to sulfur(VI) fluoride exchange (SuFEx) click chemistry. The generated molecules contain pharmaceutically important amide and -SO2F moieties for application in the discovery of new therapeutics.

Clickable coupling of carboxylic acids and amines at room temperature mediated by SO2F2: a significant breakthrough for the construction of amides and peptide linkages.

The construction of amide bonds and peptide linkages is one of the most fundamental transformations in all life processes and organic synthesis. The synthesis of structurally ubiquitous amide motifs is essential in the assembly of numerous important molecules such as peptides, proteins, alkaloids, pharmaceutical agents, polymers, ligands and agrochemicals. A method of SO2F2-mediated direct clickable coupling of carboxylic acids with amines was developed for the synthesis of a broad scope of amides in a simple, mild, highly efficient, robust and practical manner (>110 examples, >90% yields in most cases). The direct click reactions of acids and amines on a gram scale are also demonstrated using an extremely easy work-up and purification process of washing with 1 M aqueous HCl to provide the desired amides in greater than 99% purity and excellent yields.

Discovery of novel arylethenesulfonyl fluorides as potential candidates against methicillin-resistant of Staphylococcus aureus (MRSA) for overcoming multidrug resistance of bacterial infections.

The multidrug-resistant Staphylococcus aureus (MRSA) is one of the most prevalent human pathogens involved in many minor to major disease burdens throughout the world. Inhibition of biofilm formation is an attractive strategy to treat diseases associated with MRSA infection. In the present investigation, a series of functional group diverse (hetero)aryl fluorosulfonyl analogs were designed, synthesized and tested as antibacterial agents against Staphylococcal spp., and as anti-biofilm candidates. Compounds 8, 15, and 67 were found to possess potent in vitro antibacterial activity among this class of sulfonyl fluorides (MIC = 0.818 ±â€¯0.42, 0.840 ±â€¯0.37 and 0.811 ±â€¯0.37 µg/mL respectively). The analogs 8, 15, 36, and 67 exhibited outstanding anti-biofilm properties compared to other available synthetic antibiotics. The efficacy of synthetic analogs displayed membrane-damaging effect and they are also validated by cellular content release assay. The insight physiological changes were explored by studying the intracellular redox activities through changing cyclic voltammetric (CV) method. The compounds 8, 15, 22, 32, 36, 51, and 67 were found to participate in the interfering in the electron transport chain (ETC) of MRSA. The analogs 8, 15, and 67 possess great potentiality for discovery and development of anti-staphylococcal drugs to treat the MRSA infections.

A Rh-Catalyzed Air and Moisture Tolerable Aldehyde (Ketone)-Directed Fluorosulfonylvinylation of Aryl C( sp2)-H Bonds.

The first Rh-catalyzed activation of ortho sp2 C-H bonds of aldehydes (ketones) for monoselective coupling with ethenesulfonyl fluoride was accomplished without covalent or transient preinstallation of imines. The 42 examples revealed that the developed method has the advantage of a wide scope and functional-group tolerability. Application of this method for complicated natural product modification was also accomplished.

Recent Developments on Phenstatins as Potent Antimitotic Agents.

BACKGROUND: Phenstatin and their derivatives display remarkable antiproliferative activity toward a wide variety of preclinical tumor models. Structural simplicity and excellent stability of phenstatins offer a stimulating premise for developing various derivatives with profound antimitotic activity and excellent cytotoxicity. OBJECTIVE: To do analysis of literature that phenstatins derivatives inhibit tubulin polymerization through their interaction at the colchicine binding site of microtubules and arrest the G2/M phase of the cell cycle. In addition, phenstatin derivatives are undergoing clinical evaluation as vascular targeting/disrupting agents and also exhibit direct antiangiogenic properties. METHODS: An organised well designed and appropriately managed search of bibliographic databases for peer-reviewed research literature using a focused review question and inclusion/ exclusion criteria has been done for this article. CONCLUSION: In this review article, the synthesis and structure-activity relationships of phenstatin and a wide number of their reported analogues with modifications to ring A, ring B, and to the keto position are discussed in the perspective of medicinal chemistry with proper conclusion.

Recent Development of Sulfonyl or Sulfonamide Hybrids as Potential Anticancer Agents: A Key Review.

Cancer is the second leading cause of death worldwide. There is always a huge demand for novel anticancer drugs and diverse new natural or synthetic compounds are developed continuously by scientists. Presently, a large number of drugs in clinical practice have showed pervasive side effect and multidrug resistance. Sulfonyl or sulfonamide hybrids became one of the most attractive subjects due to their broad spectrum of pharmacological activities. Sulfonyl hybrids were broadly explored for their anticancer activities and it was found that they possess minimum side effect along with multi-drug resistance activity. This review describes the most recent applications of sulfonyl hybrid analogues in anticancer drug discovery and further discusses the mechanistic insights, structure-activity relationships and molecular docking studies for the potent derivatives.

Sonogashira Reaction Using Arylsulfonium Salts as Cross-Coupling Partners.

Triarylsulfonium, alkyl- and fluoroalkyl(diaryl)sulfonium, and aryl(dialkyl)sulfonium triflates are successfully used as a new family of cross-coupling participants in the Sonogashira reaction as aryldiazonium, diaryliodonium, and tetraphenylphosphonium salts. It was found that terminal alkynes reacted mildly with triarylsulfonium or (2,2,2-trifluoroethyl)diphenylsulfonium triflate at room temperature under Pd- and Cu-cocatalysis to give the corresponding arylalkynes in up to >99% yield. This protocol represents the first use of arylsulfonium salts as cross-coupling partners in the Pd/Cu-catalyzed Sonogashira reaction.

Neutrophil to lymphocyte ratio as prognostic indicator for patients with esophageal squamous cell cancer.

BACKGROUND: This study aimed to evaluate the correlation between neutrophil to lymphocyte ratio (NLR) with overall survival (OS) of esophageal squamous cell carcinoma (ESCC) patients. METHOD: Records of patients with diagnosed ESCC were reviewed. Leukocyte counts and patients' characteristics were extracted from their clinical records to calculate NLR. Correlation between NLR and baseline characteristics with overall survival (OS) was then analyzed using Cox regression. The patients were then separated into higher and lower NLR groups according to median NLR. OS was further compared between the 2 groups. RESULTS: A total of 1281 patients were included in the study. Cox regression analysis showed a significant correlation of NLR with OS of ESCC patients. The median pretreatment NLR was identified as 2.86. Higher NLR was associated with worse prognosis in terms of OS. CONCLUSIONS: Pretreatment NLR is independently associated with OS of ESCC patients. Therefore, NLR may be used as a predictive indicator for pretreatment evaluation and adjustment of treatment regimen.

Chemoselective synthesis of diaryl disulfides via a visible light-mediated coupling of arenediazonium tetrafluoroborates and CS2.

A highly efficient and chemoselective method for the synthesis of diaryl disulfides is developed via a visible light-promoted coupling of readily accessible arenediazonium tetrafluoroborates and CS2. This practical and convenient protocol provides a direct pathway for the assembly of a series of disulfides in an environmentally friendly manner with good to excellent yields.

Synthesis of benzo[d]thiazole-hydrazone analogues: molecular docking and SAR studies of potential H+/K+ ATPase inhibitors and anti-inflammatory agents.

A series of new benzo[d]thiazole-hydrazones were synthesized and characterized by analytical and spectroscopic techniques. All the compounds were screened for their in vitro inhibition of H+/K+ ATPase and anti-inflammatory effects. The results revealed that compounds 6-8, 13-15, 18-20, 22, 23 and 27-30 displayed excellent inhibitory activity against H+/K+ ATPase, and their IC50 values were lower than those of the standard compound omeprazole. Compounds 2-5, 9-12, 28 and 30 exhibited better anti-inflammatory activity in comparison to the standard compound indomethacin. Studies of the structure-activity relationship (SAR) showed that electron-donating groups (OH and OCH3) favored inhibitory activity against H+/K+ ATPase, whereas electron-withdrawing groups (F, Cl, Br and NO2) favored anti-inflammatory activity, and derivatives with both electron-donating (OH and OCH3) and electron-withdrawing (Br) groups (16-18) displayed reasonable activity, whereas aliphatic analogues (24-26) exhibited less activity and heterocyclic analogues (27-30) displayed moderate activity in both biological studies. Molecular docking studies were performed for all the synthesized compounds, among which compounds 19 and 20 exhibited the highest docking scores for inhibitory activity against H+/K+ ATPase, whereas compounds 10 and 12 displayed the highest docking scores for anti-inflammatory activity.

Palladium-catalyzed Mizoroki-Heck-type reactions of [Ph2SRfn][OTf] with alkenes at room temperature.

The first Pd-catalyzed Mizoroki-Heck-type reaction of [Ph2SRfn][OTf] with alkenes is described. The reaction of [Ph2SRfn][OTf] (Rfn = CF3, CH2CF3) with alkenes in the presence of 10 mol% Pd[P(t-Bu)3]2 and TsOH at room temperature provided the corresponding phenylation products in good to high yields. The bases that benefit the traditional Mizoroki-Heck reactions severely inhibited the transformation with [Ph2SRfn][OTf], whereas acids significantly improved the reaction. This protocol supplies a new class of cross-coupling partners for Mizoroki-Heck-type reactions and gains important insights into the reactivity of phenylsulfonium salts either with or without fluorine-containing alkyl groups as the promising phenylation reagents in organic synthesis.

Palladium-Catalyzed Arylation of Arylboronic Acids with Yagupolskii-Umemoto Reagents.

A Pd-catalyzed Suzuki cross-coupling of arylboronic acids with Yagupolskii-Umemoto reagents was explored. In contrary to trifluoromethylations, the Pd-catalyzed reaction of R-B(OH)2 and [Ar2 SCF3 ](+) [OTf](-) provided the arylation products (R-Ar) in good to high yields. The reaction confirms that the S-Ar bonds of [Ar2 SCF3 ](+) [OTf](-) can be readily cleaved in the presence of Pd complexes. The relatively electron-poor aryl groups of asymmetric [Ar(1) Ar(2) SCF3 ](+) [OTf](-) salts are more favorably transferred compared to the electron-rich ones. This reaction represents the first report of utilization of [Ar2 SCF3 ](+) [OTf](-) as arylation reagents in organic synthesis.