Sulfonate Esters Research Articles

EnT-Mediated N-S Bond Homolysis of a Bifunctional Reagent Leading to Aliphatic Sulfonyl Fluorides.

Sulfur(VI) fluoride exchange (SuFEx) gives rise to a plethora of high-valent sulfur linkages; however, the availability of (aliphatic) sulfonyl fluoride manifolds lag behind, owing to the limited sources of introducing the SO2F moiety via a classical two-electron approach. Recently, radical-based methodologies have emerged as a complementary strategy to increase the diversity of accessible click partners. In this work, synthesis of a bench-stable sulfamoyl fluoride reagent is presented, which may undergo sigma-bond homolysis upon visible-light-induced sensitization to form protected β-amino sulfonyl fluorides from alkene feedstocks. Notably, this offers an appealing strategy to access various building blocks for peptido sulfonyl fluorides, relevant in a medicinal chemistry context, as well as an intriguing entry to β-ammonium sulfonates and β-sultams, from alkenes. Densely functionalized 1,3-sultones were obtained by employing allyl alcohols as substrates. Surprisingly, allyl chloride-derived β-imino sulfonyl fluoride underwent S-O bond formation and ring closure to yield rigid cyclopropyl β-imino sulfonate ester under SuFEx conditions. Furthermore, by engaging a thiol-based hydrogen atom donor in the reaction, the reactivity of the same reagent can be tuned toward the direct synthesis of aliphatic sulfonyl fluorides. Mechanistic experiments indicate an energy transfer (EnT)-mediated process. The transient sulfonyl fluoride radical adds to the alkene and product formation occurs upon either radical-radical coupling or hydrogen atom transfer (HAT), respectively.

Synthesis, Biological Evaluation and Molecular Modeling Studies of Naphthoquinone Sulfonamides and Sulfonate Ester Derivatives as P2X7 Inhibitors.

ATP acts in the extracellular environment as an important signal, activating a family of receptors called purinergic receptors. In recent years, interest in the potential therapeutics of purinergic components, including agonists and antagonists of receptors, has increased. Currently, many observations have indicated that ATP acts as an important mediator of inflammatory responses and, when found in high concentrations in the extracellular space, is related to the activation of the P2X7 purinergic receptor. In this sense, the search for new inhibitors for this receptor has attracted a great deal of attention in recent years. Sulfonamide derivatives have been reported to be potent inhibitors of P2X receptors. In this study, ten naphthoquinone sulfonamide derivatives and five naphthoquinone sulfonate ester derivatives were tested for their inhibitory activity on the P2X7 receptor expressed in peritoneal macrophages. Some compounds showed promising results, displaying IC50 values lower than that of A740003. Molecular docking and dynamic studies also indicated that the active compounds bind to an allosteric site on P2X7R. The binding free energy indicates that sulfonamides have an affinity for the P2X7 receptor similar to A740003. Therefore, the compounds studied herein present potential P2X7R inhibition.

Design, synthesis and evaluation of halogenated phenazine antibacterial prodrugs targeting nitroreductase enzymes for activation.

It is of great importance to develop new strategies to combat antibiotic resistance. Our lab has discovered halogenated phenazine (HP) analogues that are highly active against multidrug-resistant bacterial pathogens. Here, we report the design, synthesis, and study of a new series of nitroarene-based HP prodrugs that leverage intracellular nitroreductase (NTR) enzymes for activation and subsequent release of active HP agents. Our goals of developing HP prodrugs are to (1) mitigate off-target metal chelation (potential toxicity), (2) possess motifs to facilitate intracellular, bacterial-specific HP release, (3) improve water solubility, and (4) prevent undesirable metabolism (e.g., glucuronidation of HP's phenol). Following the synthesis of HP-nitroarene prodrugs bearing a sulfonate ester linker, NTR-promoted release experiments demonstrated prodrug HP-1-N released 70.1% of parent HP-1 after 16 hours (with only 6.8% HP-1 release without NTR). In analogous in vitro experiments, no HP release was observed for control sulfonate ester compounds lacking the critical nitro group. When compared to parent HP compounds, nitroarene prodrugs evaluated during these studies demonstrate similar antibacterial activities in MIC and zone of inhibition assays (against lab strains and clinical isolates). In conclusion, HP-nitroarene prodrugs could provide a future avenue to develop potent agents that target antibiotic resistant bacteria.

Modification of sulfonated poly(arylene ether nitrile) proton exchange membranes by poly(ethylene-co-vinyl alcohol).

The modification of the physicochemical properties of sulfonated poly(arylene ether nitrile) (SPAEN) proton exchange membranes was demonstrated by poly(ethylene-co-vinyl alcohol) (EVOH) doping (named SPAEN-x%). By controlling the temperature during membrane preparation, the side reactions of the sulfonic acid groups to form sulfonic acid esters were effectively prevented, greatly reducing the proton conductivity of the membranes. Due to the flexible chain of EVOH, SPAEN-8% showed a relatively high elongation of 30.2%, which enhanced the aromatic polymers' flexibility. The SPAEN-2% membrane exhibited proton conductivity of 166, 55, and 9.6 mS cm-1 at 95%, 70%, and 50% relative humidity, respectively, higher than those of the other SPAEN-x% membranes and even comparable to that of Nafion 212. The water uptake, morphological study, and through-plane proton conductivity of the membranes were studied and discussed. The results suggest that EVOH doping can be used as an effective strategy to improve SPAEN-based proton exchange membranes' performance.

A CAPILLARY GC-MS ANALYSIS OF RESIDUAL ETHANESULFONATES IN TENELIGLIPTIN

The presence of residual sulfonate esters in drugs is potentially genotoxic impurities (PGIs), thus demanding a need for a specific method to quantify them in the drug as per regulatory authorities’ guidelines. Accordingly, a GC-MS procedure was optimized and proved for the assessment of ethyl ethanesulfonate (EES) and isopropyl ethanesulfonate (IPES) in the Teneligliptin drug. The detection (LOD) and quantification (LOQ) limit values of EES and IPES were 3.75 and 11.25 ppm, respectively. A linear relationship was observed between 11.25 and 56 ppm. The mean recoveries of EES and IPES were 102.65 and 102.21%. The method is precise, accurate, specific, and linear; thus it can be employed to measure the EES and IPES in Teneligliptin and other gliptins.

The flow behavior of powder stearin-based methyl ester sulfonates and the effect of glidant

The preparation and behavior of powder stearin-based methyl ester sulfonates (MES) with the addition of builder as a glidant agent was studied. MES is an anionic surfactant and its performance is equivalent to petroleum-based linear alkylbenzene sulfonates (LAS), the workhorses of the detergent industry. At the same time, zeolites or soda ash were the alternative builders for non-phosphate-based detergent. The behavior of powder MES properties was measured in terms of morphology, particle size, cohesion, caking, and compaction. Before that, these palm stearin-based MES of carbon chain 16–18 with ratios of 98:2, 80:20, and 60:40 in flakes were ground using a high shear mixer by 23,000 rpm to produce powder particles. Decreasing the particle size of MES powder can reduce the powder's cohesion, caking, and compaction. The addition of zeolite or soda ash as a glidant in powdered MES can improve the caking behavior. The high stearic in MES greatly influenced getting fine particle powders and required more glidant agents. This powder MES with excellent powder characteristics can perform well as a bio-based cleaning product.

A facile synthesis of sulfonate esters from phenols using catalytic KF/NFSI and K2CO3

A facile synthesis of sulfonate esters from phenols using catalytic KF/NFSI and K2CO3

An Expedient Iodine‐Catalyzed Synthesis of Unsymmetrical Thiosulfonates by Sulfonylation of Thiols using Sulfonyl hydrazides in the Presence of Oxone

AbstractA metal‐free and green iodine‐catalyzed protocol is described herein for the synthesis of unsymmetrical thiosulfonates by sulfonylation of thiols using I2/Oxone. It's shown that oxidative cross‐coupling of thiyl radicals with sulfonyl radicals – generated from thiols and sulfonyl hydrazides, respectively, by the redox chemistry between thiol/Oxone and I2/Oxone – occurs in a facile manner at rt, providing access to unsymmetrical thiosulfonates. Diverse unsymmetrical thiosulfonates are synthesized in good‐to‐excellent isolated yields by the reactions of aryl/(hetero)aryl/alkyl thiols with a variety of aryl/(hetero)aryl/alkyl/benzyl sulfonyl hydrazides. The protocol can be further extended to the synthesis of alkyl/aryl sulfonate esters by the reactions of sulfonyl hydrazides with alcohols/phenols using I2/Oxone.

Study on the combined dust suppression effect of sodium alginate and sodium fatty acid methyl ester sulfonate

• In-depth study of coal dust wetting mechanism. • Application of molecular dynamics simulation in dust suppressants. • Study on the mechanism of dust suppression by combining different surfactants. To further improve the effect of dust control in coal mines and protect the health of workers, the effect of sodium alginate (SA) on the dust suppression ability of sodium methyl ester sulfonate (MES) was studied using molecular dynamics simulation. Scanning electron microscopy and X-ray photoelectron spectroscopy analyses were performed to compare the dust suppression effect of the SA/MES dust suppressant compound to MES by itself. The results show that when SA is present, the coal dust bonds together more, agglomerates into large particles, and settles. This finding is also consistent with the results of molecular dynamics simulations. In the analysis of relative concentrations and mean square displacement, the presence of SA can reduce the water diffusion on the coal surface, making it easier for coal dust to agglomerate. In addition, we analyzed the mode of action of SA through radial distribution and electrostatic potential, and determined that SA forms a unique networking chain structure to capture and retain water molecules. SA increases the probability of interaction between water and surfactant, thus increasing the amount of adsorption. This study provides a more in-depth understanding of the dust suppression mechanism of mixed dust suppressants.

Isoniazid Linked to Sulfonate Esters via Hydrazone Functionality: Design, Synthesis, and Evaluation of Antitubercular Activity.

Isoniazid (INH) is one of the key molecules employed in the treatment of tuberculosis (TB), the most deadly infectious disease worldwide. However, the efficacy of this cornerstone drug has seriously decreased due to emerging INH-resistant strains of Mycobacterium tuberculosis (Mtb). In the present study, we aimed to chemically tailor INH to overcome this resistance. We obtained thirteen novel compounds by linking INH to in-house synthesized sulfonate esters via a hydrazone bridge (SIH1–SIH13). Following structural characterization by FTIR, 1H NMR, 13C NMR, and HRMS, all compounds were screened for their antitubercular activity against Mtb H37Rv strain and INH-resistant clinical isolates carrying katG and inhA mutations. Additionally, the cytotoxic effects of SIH1–SIH13 were assessed on three different healthy host cell lines; HEK293, IMR-90, and BEAS-2B. Based on the obtained data, the synthesized compounds appeared as attractive antimycobacterial drug candidates with low cytotoxicity. Moreover, the stability of the hydrazone moiety in the chemical structure of the final compounds was confirmed by using UV/Vis spectroscopy in both aqueous medium and DMSO. Subsequently, the compounds were tested for their inhibitory activities against enoyl acyl carrier protein reductase (InhA), the primary target enzyme of INH. Although most of the synthesized compounds are hosted by the InhA binding pocket, SIH1–SIH13 do not primarily show their antitubercular activities by direct InhA inhibition. Finally, in silico determination of important physicochemical parameters of the molecules showed that SIH1–SIH13 adhered to Lipinski’s rule of five. Overall, our study revealed a new strategy for modifying INH to cope with the emerging drug-resistant strains of Mtb.

Controlling tosylation versus chlorination during end group modification of PCL

Synthetic biodegradable materials are commonly used to create constructs for medical devices and tissue engineered constructs. However, many of the homopolymers used in FDA approved devices such as poly(ε-caprolactone) (PCL), poly(lactic acid), or poly(carbonates) lack biogically relevant functional groups to steer biological responses in a controlled fashion. Commonly, an interconversion of the end groups is required to insert addressable moieties for the attachment of biologically active groups. In this study, the activation of the hydroxyl groups of a low molecular weight PCL-diol to the corresponding p-toluene sulfonate ester using p-toluenesulfonyl chloride was performed in both dichloromethane (DCM) and dimethylformamide (DMF). To our initial surprise, we only yielded the chlorinated product in DMF, while in DCM the tosylate ester was obtained. In a small series of reactions, we studied the solvent dependent switchability between tosylation and chlorination on PCL. We concluded that in polar aprotic solvents (DMF and dimethylsulfoxide), we rapidly and efficiently converted the hydroxyl into the chloride group, whereas in inert solvents (DCM and chloroform) we yielded the tosylated product. The data suggested that solvation effects of the polar aprotic solvents led to a Sn2 reaction of the tosyl group by the chloride. Furthermore, we utilized a polyethylene glycol (PEG) polymer to show translatability of the chlorination reaction to other (biomedical) polymers. This work highlights a new reaction pathway during the tosylation of a polymer end group, and presents a new useful strategy to insert clickable groups on synthetic polymers that are only soluble in polar aprotic solvents.

Functionalization of Sulfonic Acid to Sulfonic Ester Using Diazo Compound under Mild Reaction Conditions in the Absence of Additives

AbstractSulfonate esters are important owing to their special bioactivities. Nevertheless, severe reaction conditions, use of expensive catalysts along with additives and the numerous side reactions in the previously reported methods demand the development of valid approaches for the synthesis of aryl sulfonate esters. Herein, we report a facile synthetic strategy utilizing the VIV based catalyst for the carbene insertion into the O−H bond of sulfonic acids to afford sulfonate esters up to 90 % yield under mild reaction conditions. All the synthesized sulfonate esters were fully characterized by using standard spectroscopic and analytical techniques such as NMR, IR, ESI‐MS and single crystal XRD analysis.

An Unexpended Stereocontrolled Rearrangement of Ethyl 4‐Hydroxy‐4‐(substituted phenyl)‐2‐butynoate to Tetrasubstituted Alkenes with MeSOCl 2

In this study, syn-selective tetrasubstituted alkene derivatives were synthesized from ethyl 4-hydroxy-4-(substituted phenyl)-2-butynoate under classical mesylation reaction conditions. The structures of the obtained products were determined by 1H-NMR,13C-NMR spectroscopy, HRMS, and X-ray analysis.

A novel CO2 sensitive and recyclable viscoelastic fluid system for fracturing

Hydraulic fracturing is one of the most commonly used processes of stimulating oil and gas wells to improve the production in low permeability reservoirs or damaged wells. In response to the serious water waste caused by the flowback fluid after the fracturing operation and the huge environmental pressure, a novel CO2 sensitive and recyclable viscoelastic fracturing fluid was developed. This CO2 sensitive property allows fracturing fluids to be recycled. The system consists of viscoelastic surfactants called fatty methyl ester sulfonates (FMES), triethylenetetramine and NaCl. The system shows a strong sensitivity to CO2. When the system is repeatedly contacted and separated from CO2, the viscosity rises and falls rapidly and regularly. The experiments of viscoelasticity, shear resistance and microstructure confirmed that the increasing viscosity of the system after contacting with CO2 was caused by the formation of viscoelastic fluid. When the system leak-off into the formation matrix, the microstructure of the system will be rapidly destroyed under the action of hydrocarbons, and the viscosity will drop to 1.225 mPa·s. Low viscosity after destroying reduces the retention of the system in the formation, resulting in formation damage rate of less than 35%. This research not only provides high-performance, low-cost fracturing fluids, but also provides new insights for the recovery and utilization of fracturing fluids.

Polymers with Pendant Water‐Soluble Tetrafluorobenzene Sulfonic Acid Activated Esters: Synthesis, Stability, and Use for Glycopolymers in Water

Front Cover: In article number 2200072, Tomonari Tanaka and co-workers synthesize a novel monomer and polymer bearing water-soluble activated ester groups, tetrafluorobenzene sulfonic acid esters, with a pentandiyl linker. These are stable and can be used for synthesizing glycopolymers in water. Synthesis of functional polymers in water are further developed.

Liquid Smoke from Coconut Shell Pyrolysis Process on Palm Surfactant Based Liquid Hand Soap

The use of synthetic antibacterial liquid hand soap such as triclosan has begun to be avoided. Therefore it is necessary to find an antibacterial alternative that is safe for the skin and friendly to the environment. One of the environmentally friendly antibacterial alternatives is liquid smoke resulting from the pyrolysis process from coconut shells. The purpose of this study was to obtain the right concentration of liquid smoke for liquid hand soap made from palm MES surfactants and glycerol. The stages of the research were raw material analysis, liquid soap formulation (surfactant methyl ester sulfonate 7.5%, surfactant diethanolamide 5%, palm glycerol 9%, sodium chloride 1%, liquid smoke grade I, and distilled water). The treatments in this study were the addition of 1, 3, and 5% grade I liquid smoke. The next stage is an analysis of the physicochemical properties of the resulting liquid soap product, quality test was carried out based on SNI 2588: 2017, and a product effectiveness test. Liquid soap with the addition of 1% liquid smoke showed the best results with a density value of 1.037 g cm-3, specific gravity 1.04, viscosity 11,560 cP, surface tension 29.08 dyne cm-1, pH 7.2, free fatty acids 0.27%, ingredients insoluble in ethanol 0.14%, the total active ingredient is 12.52%, the number of plates is 990 CFU g-1, the colony reduction is 61.13%, and has the minimal pungent aroma.

Synthesis and 18F Labeling of Alkenyl Sulfonyl Fluorides via an Unconventional Elimination Pathway.

A successful Cu-catalyzed addition of both Cl and SO2OCF2H groups into alkenes allows us to discover the unusual reactivity of the SO2OCF2H group. As opposed to common sulfonic esters (RSO2-O-R'), in which the R' group is highly electrophilic, the SO2 moiety demonstrates higher electrophilicity in RSO2-OCF2H. The unexpected reactivity is further developed not only as a synthetic tool for well-functionalized alkenyl sulfonyl fluorides but also for the first 18F labeling of alkenyl sulfonyl fluorides.

A succinct synthesis of (25R)-cholesta-5,7-diene-3β,26-diol from ergosterol

An efficient seven-step procedure is described for the synthesis of (25R)-cholesta-5,7-diene-3β,26-diol from commercially available ergosterol in an overall yield of 25%. The synthesis features Julia-Kocienski olefination of the aldehyde with benzothiazole sulfone ester in presence of LiHMDS followed by reduction of the alkene.

Synthesis, Antibacterial and Insecticidal Activities of Novel Capsaicin Derivatives Containing a Sulfonic Acid Esters Moiety.

In order to develop an efficient and broad-spectrum bactericide, a series of novel capsaicin derivatives containing a sulfonic acid esters moiety was synthesized. The structure of these compounds were confirmed by nuclear magnetic resonance spectroscopy (NMR) and high-resolution mass spectrum (HRMS). The results of the bioactivities revealed that some target compounds exhibited remarkable antibacterial activity. Compound 3b exhibited the highest activities against Pseudomonas syringae pv. actinidiae (Psa), Xanthomonas oryzae pv. oryzae (Xoo), and Xanthomonas axonopodis pv. citri (Xac), and the values were 86, 54, and 92% at 50 μg/ml, respectively, which were higher than were for thiodiazole copper (87, 34, and 77%) and bismerthiazol (87, 37 and 75%). Although some compounds also showed certain activity against Spodoptera frugiperda, it was weaker than the positive controls monosultap and mulfoxaflor. Thus, the bioassay results recommend that these newly designed and synthesized scaffolds should be used as a bactericide lead compound rather than an insecticide lead compound.

Synthesis and Bioactivities of Novel Piperonylic Acid Derivatives Containing a Sulfonic Acid Ester Moiety.

The crop loss caused by bacteria has increased year by year due to the lack of effective control agents. In order to develop efficient, broad-spectrum, and structurally simple agricultural bactericide, the structure of piperonylic acid was modified and a series of novel piperonylic acid derivatives containing a sulfonic acid ester moiety was synthesized. Bioassay results indicated the compounds exhibited significantly antibacterial activities. Among them, compound 41 exhibited excellent antibacterial activities against Pseudomonas syringae pv. Actinidiae (Psa), with inhibitory value 99 and 85% at 100 μg/ml and 50 μg/ml, respectively, which was higher than that of thiodiazole-copper (84 and 77%) and bismerthiazol (96 and 78%). In addition, some compounds also showed moderate insecticidal activity against Spodoptera frugiperda. The abovementioned results confirm the broadening of the application of piperonylic acid, with reliable support for the development of novel agrochemical bactericide.