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Ischemia reperfusion injury is responsible for impaired graft functioning in organ transplants, cerebral dysfunction, ischemic heart diseases, systemic inflammatory response syndrome, gastrointestinal dysfunction, and multiple organ dysfunction syndromes. Intracellular pH is critical for cell survival in ischemia reperfusion injury. Sodium hydrogen exchanger I and carbonic anhydrase II are critical in the regulation of intracellular pH. Inhibition of sodium hydrogen exchanger I and carbonic anhydrase II during reperfusion is found to ameliorate ischemia reperfusion injury separately. An attempt is made to synthesize dual inhibitors of sodium hydrogen exchanger and carbonic anhydrase to have better potential drug molecule in ischemia reperfusion injury treatment. The hydroxybenzotriazole is considered as a central pharmacophore for this dual activity and 12 derivatives are synthesized. All derivatives are tested for sodium hydrogen exchanger I and carbonic anhydrase II inhibitory activity. The tosylate derivative (12) is found to be the most potent derivative with IC50 158.7± 8.4 μM for carbonic anhydrase II and 31.07 ± 1.06 μM for sodium hydrogen exchanger I. Although the potency is less than standard drugs but this is the first report of dual inhibitor of carbonic anhydrase II and sodium hydrogen exchanger.

In the present work, we carried out hydroxybenzotriazole (HOBT) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCl)-mediated synthesis of new N'-(1,3-benzothiazol-2-yl)-arylamides C1-18 in high yields under relatively milder reaction conditions using dimethyl formamide as solvent. Synthesized compounds were characterized by FTIR, 1H-NMR, 13C-NMR and HRMS spectral data. The MIC values of synthesized compounds C1-18 were determined by the broth microdilution method using Mueller Hinton medium. Tested compounds showed variable activity against the tested Gram-positive and Gram-negative bacterial strains. Compounds C3, C5, C9, C13-15 and C17 exhibited promising activity against Staphylococcus aureus NCIM 5021 with MIC values in the range of 19.7–24.2 μM. Among all tested compounds, C13 possessing thiophene ring attached to the benzothiazole moiety via amide linkage exhibited maximum activity against S. aureus NCIM 5022 with MIC of 13.0 μM. Compound C13 showed maximum activity against S. aureus ATCC 43300 with MIC of 15.0 μM and exhibited bactericidal activity against this strain in minimum bactericidal concentration determination. This compound also eliminated S. aureus ATCC 43300 strain after 24-h exposure indicating its bactericidal activity. ADMET calculation showed favourable pharmacokinetic profile of synthesized compounds C1-18.

Azoles are an important class of small molecules in pharmaceuticals and in pesticides which are found in surface water and effluents of wastewater treatment plants. With increasing research on novel characteristics of such compounds, they are considered emerging contaminants, thus, the efficiency of existing technologies for their treatment becomes an important matter. Peroxidases have proven to be effective in transformation of phenols and anilines via radical coupling. Here, the feasibility of oxidative polymerization of selected azoles with soybean peroxidase is demonstrated. The sensitivity of such treatment to the most important parameters, pH, enzyme activity and peroxide concentration, was investigated. Enzymatic treatment was shown to be effective with ≥70% transformation efficiency in all cases, with hydroxybenzotriazole having the highest efficiency among the substrates tested, thus providing a baseline for future study of real wastewater and environmental samples. Radical-coupling products after treatment were shown by mass spectrometry to be dimers and trimers and structures are proposed based on regiochemistry predicted from radical spin-density computations. Ionization energy and reduction potential of the compounds studied were also computed to look for a correlation with enzyme reactivity.

A simple one-pot synthesis of N-substituted benzimidazoles from aromatic carboxylic acids and aromatic 1,2-diamines in the presence of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate/hydroxybenzotriazole (HATU/HOBT) and N,N-diisopropylethylamine in DMF at 100°C, featuring good to excellent yields and easy workup, is developed. The protocol can be scaled to gram quantities, and no chromatographic purification is required.

Synthetic cannabinoid receptor agonists (SCRAs) remain a prolific class of new psychoactive substances (NPS) and continue to expand rapidly. Despite the recent identification of hydroxybenzotriazole (HOBt) containing SCRAs in synthetic cannabis samples, there is currently no information regarding the pharmacological profile of these NPS with respect to human CB1 and CB2 receptors. In the current study, a series consisting of seven HOBt indole-, indazole-, and 7-azaindole-carboxylates bearing a range of N-alkyl substituents were synthesized and pharmacologically evaluated. Competitive binding assays at CB1 and CB2 demonstrated that all analogues except a 2-methyl-substituted derivative had low affinity for CB1 (Ki = 3.80-43.7 μM) and CB2 (Ki = 2.75-18.2 μM). A fluorometric functional assay revealed that 2-methylindole- and indole-derived HOBt carboxylates were potent and efficacious agonists of CB1 (EC50 = 12.0 and 63.7 nM; Emax = 118 and 120%) and CB2 (EC50 = 10.9 and 321 nM; Emax = 91 and 126%). All other analogues incorporating indazole and 7-azaindole cores and bearing a range of N1-substituents showed relatively low potency for CB1 and CB2. Additionally, a reporter assay monitoring β-arrestin 2 (βarr2) recruitment to the receptor revealed that the 2-methylindole example was the most potent and efficacious at CB1 (EC50 = 131 nM; Emax = 724%) and the most potent at CB2 (EC50 = 38.2 nM; Emax = 51%). As with the membrane potential assay, the indazole and other indole HOBt carboxylates were considerably less potent at both receptors, and analogues comprising a 7-azaindole core showed little activity. Taken together, these data suggest that NNL-3 demonstrates little CB1 receptor activity and is unlikely to be psychoactive in humans. NNL-3 is likely an unintended SCRA manufacturing byproduct. However, the synthesis of NNL-3 analogues proved simple and general, and some of these showed potent cannabimetic profiles in vitro, indicating that HOBt esters of this type may represent an emerging class of SCRA NPS.

A series of novel 5-chloro-2-(thiophen-2-yl)-7,8-dihydroquinoline-6-carboxamides was designed, synthesized, and evaluated for antitubercular activity. The required 5-chloro-2-(thiophen-2-yl)-7,8-dihydroquinoline-6-carboxylic acid intermediate was prepared by oxidizing the respective aldehyde with sodium chlorite and 30% H2O2. Further, the acid was coupled with various aryl, alkyl, and heterocyclic amines using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and hydroxybenzotriazole to give the desired 5-chloro-2-(thiophen-2-yl)-7,8-dihydroquinoline-6-carboxamides in excellent yields. All the new compounds were characterized by their NMR and mass spectral analysis. Screening of all new compounds for in vitro antimycobacterial activity against M. tuberculosis H37Rv (Mtb) resulted in five analogs with MIC 3.12 µg/cm3 as promising antitubercular agents with lower cytotoxicity profiles.

1-Hydroxybenzotriazole (HOBt) is a nucleophilic additive widely utilized in synthetic chemistry. During process optimization for an amidation reaction employing HOBt, the presence of two hydrazide ...

In the micelle of PS-750-M, the presence of 3° amides from the surfactant proline linker mimics dimethylformamide, dimethylacetamide, and N-methyl-2-pyrrolidone. The resultant micellar properties enable extremely fast amide couplings mediated by 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide (without hydroxybenzotriazole), rather than expensive and specialized coupling agents. Conditions have been developed wherein products precipitate, and isolation by filtration completely avoids the use of organic solvent. This methodology is scalable and avoids product epimerization.

Lignin is a highly abundant aromatic polymer in nature, but its controlled cleavage or cross-linking is a major challenge and currently hindering industrial applicability. Laccase (L) and laccase/mediator systems (LMS) are promising tools for enzymatic lignin modification, but to date, their overall reaction outcome is hard to predict and control. This research aimed to understand the reactivity of native and sulfonated β-O-4 linked lignin structures in L and LMS treatments. Trametes versicolor laccase, and the mediator hydroxybenzotriazole (HBT) were used, and reaction products were analyzed using UHPLC-MS n and MALDI-TOF-MS. Polymerization was observed for both the native and sulfonated phenolic compounds, suggesting that sulfonation does not affect radical coupling of the phenolic lignin subunits. In contrast, sulfonation of the non-phenolic lignin structure prevented C α oxidation and cleavage by L/HBT, which was explained by an increased C α -H bond dissociation energy of ∼10 kcal mol -1 upon sulfonation. Overall, our results indicate that lignin sulfonation drives the overall outcome of LMS incubations towards polymerization.

Laccase-mediator systems (LMS) have been widely studied for their capacity to oxidize the nonphenolic subunits of lignin (70–90% of the polymer). The phenolic subunits (10–30% of the polymer), which can also be oxidized without mediators, have received considerably less attention. Consequently, it remains unclear to what extent the presence of a mediator influences the reactions of the phenolic subunits of lignin. To get more insight in this, UHPLC-MS was used to study the reactions of a phenolic lignin dimer (GBG), initiated by a laccase from Trametes versicolor, alone or in combination with the mediators HBT and ABTS. The role of HBT was negligible, as its oxidation by laccase occurred slowly in comparison to that of GBG. Laccase and laccase/HBT oxidized GBG at a comparable rate, resulting in extensive polymerization of GBG. In contrast, laccase/ABTS converted GBG at a higher rate, as GBG was oxidized both directly by laccase but also by ABTS radical cations, which were rapidly formed by laccase. The laccase/ABTS system resulted in Cα oxidation of GBG and coupling of ABTS to GBG, rather than polymerization of GBG. Based on these results, we propose reaction pathways of phenolic lignin model compounds with laccase/HBT and laccase/ABTS., This paper contributes to a more fundamental understanding of lignin modification by laccase-mediator systems.

Abnormal use of antibiotics and discharging them into the sewage systems bring about serious and dangerous harms to the environment. The present study aims at the feasibility evaluation of amoxicillin removal from the aqueous solutions by means of enzymatic oxidation by taking advantage of response surface method based on Box–Behnken model. The present study is a library research. Therefore, the experiments are carried out in a laboratory for discontinuously evaluating the effects of independent variables such as temperature, pH, contact time, enzyme activity, hydroxybenzotriazole mediator concentration and the antibiotic concentration. The remaining amoxicillin’s concentration has been determined by HPLC device. To implement the experiments, Box–Behnken model was used for measuring the variables’ mutual effects. One-way analysis of variance was used for data analysis. The results showed that enzymatic oxidation output increases with the increase in contact time and enzymatic activity as well as with a decrease in the antibiotic’s concentration. The highest and the lowest removal percentages were 91.5 and 5.36, respectively. According to the high amounts of R2 (0.974) and R2adj (0.955), it can be said that the selected model is appropriate for data analyses. Finally, a quadratic polynomial model was applied as the best model of choice for figuring out the relationships between the main variables and amoxicillin elimination output. Response surface method can be effective in amoxicillin oxidation optimization and laccase can be used for amoxicillin elimination. © 2018 Desalination Publications. All rights reserved.

Hydroxybenzotriazole is routinely used in peptide chemistry for reducing racemization due to the increased reactivity. In this article, very stable hydroxybenzotriazolyl glucosides were identified to undergo glycosidation. The reaction was hypothesized to go through the remote activation by the Tf2O at the N3-site of HOBt followed by the extrusion of the oxocarbenium ion that was attacked by the glycosyl acceptor. Further, equilibration of the zwitterionic benzotriazolyl species makes the leaving group noncompetitive and generates the nucleofuge that has been reconverted to the glycosyl donor. The reaction is mild, high yielding, fast and suitable for donors containing both C2-ethers and C2-esters as well. The regenerative-donor glycosidation strategy is promising as it enables us to regenerate the glycosyl donor for further utilization. The utility of the methodology for the oligosaccharide synthesis was demonstrated by the successful synthesis of the branched pentamannan core of the HIV1−gp120 complex.

A series of covalently linked oxasmaragdyrin-amino acid and BF2-oxasamaragdyrin–amino acid conjugates were synthesized by treating oxasmaragdyrin or its BF2 complex that contain a benzylhydroxyl group at one of the meso positions with an appropriate fluorenylmethyloxycarbonyl-protected amino acid in CH2Cl2 in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide·HCl/hydroxybenzotriazole under basic conditions at room temperature. The conjugates are stable, highly soluble in all organic solvents, and confirmed by HRMS. 1D and 2D NMR spectroscopic techniques were used to characterize the oxasmaragdyrin–amino acid conjugates. Absorption, fluorescence, and electrochemical studies of conjugates indicate that the conjugates strongly absorb and emit in visible-NIR region with decent quantum yields, singlet state lifetimes and are stable under electrochemical conditions. Furthermore, the conjugates showed minimal change in their spectral and electrochemical properties relative to that of the unconjugated oxasmaragdyrin or its BF2 complex suggest that the characteristic features of the oxasmaragdyrin and its BF2 complex is retained in the conjugates, which will be a useful feature for Near-IR fluorescence imaging and other applications.

Chlorogenic acid-chitosan conjugate was synthesized by introducing of chlorogenic acid onto chitosan with the aid of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and hydroxybenzotriazole. The data of UV-vis, FT-IR and NMR for chlorogenic acid-chitosan conjugates demonstrated the successful conjugation of chlorogenic acid with chitosan. Compared to chitosan, chlorogenic acid-chitosan conjugates exhibited increased solubility in distilled water, 1% acetic acid solution (v/v) or 50% ethanol solution (v/v) containing 0.5% acetic acid. Moreover, chlorogenic acid-chitosan conjugates showed dramatic enhancements in metal ion chelating activity, total antioxidant capacity, scavenging activities on 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) and superoxide radicals, inhibitory effects on lipid peroxidation and β-carotene-linoleic acid bleaching, and protective effect on H2O2-induced oxidative injury of PC12 cells. Particularly, chlorogenic acid-chitosan conjugate exhibited higher inhibitory effects on lipid peroxidation and β-carotene-linoleic acid bleaching than chlorogenic acid. The results suggested that chlorogenic acid-chitosan conjugates could serve as food supplements to enhance the function of foods in future.

3-Acylmethylidene-3,4-dihydroquinoxalin-2(1H)-ones are compounds which possess a wide range of physical and pharmaceutical applications. These compounds can be easily prepared by cyclocondensation of o-phenylenediamines and aroylpyruvates. Unsymmetrically substituted o-phenylenediamines can be obtained form regioisomeric mixtures of 3,4-dihydroquinoxalin-2(1H)-ones. It is often quite difficult to get a pure regioisomer and determine its structure without controlling the reaction selectivity and exploitation of complex NMR techniques (HSQC, NOESY, HMBC). This article examines the regioselectivity of the cyclocondensation between six monosubstituted o-phenylenediamines (-OMe, -F, -Cl, -COOH, -CN, -NO2) and the derivatives of p-chlorobenzoylpyruvate (ester or acid) which we studied. Six regioisomeric 3,4-dihydroquinoxalin-2(1H)-one pairs were selectively prepared and characterised. Based on our experiences, a simplified methodology for determining the structure of the regioisomers was proposed. We developed two general and highly selective methodologies starting from the same o-phenylenediamines and activated 4-chlorobenzoylpyruvates (ester or acid) enabling switching of 3,4-dihydroquinoxalin-2(1H)-one regioselectivity in a predictable manner. For comparison, all regioselective cyclocondensations were performed with the same standardized conditions (DMF, rt, 3 days), differing only by the additives p-TsOH or HOBt/DIC (hydroxybenzotriazole/N,N’-diisopropylcarbodiimide). Both selected methods are simple, general and highly regioselective (72–97%). A mechanism for the regioselectivity was also proposed and discussed. This study can be used as a guide when choosing the most optimal reaction conditions for the synthesis of the desired 3,4-dihydroquinoxalin-2(1H)-one regioisomers with the best selectivity. The demonstrated methodologies in this article may also be applied to differently substituted 3,4-dihydroquinoxalin-2(1H)-ones in general, which could expand the synthetic impact of our results.

Enzyme-based catalyzed oxidative coupling reactions (E-COCRs) are considered as viable technologies to transform a variety of pharmaceutical antibiotics. This study indicated that the extracellular fungal laccase from Pleurotus ostreatus was effective in transforming tetracycline (TC) with 1-hydroxybenzotriazole (HBT) present at varying conditions during E-COCRs. The presence of humic acid (HA) showed suppressive effect on the transformation rate constants (k) of TC, and the k values for TC decreased as HA concentration increased. It was ascribed primarily to the covalent binding between TC and HA, which reduced the apparent concentration and availability of TC in water. It is noted that TC molecules from the cross-coupling products were likely re-released under extreme conditions (pH

A thermo-activation and thermostable laccase isoenzyme (Lac 37 II) produced by Trametes trogii S0301 at 37°C was purified to apparent homogeneity by anionic exchange chromatography and sephadex G-75 chromatography, with 12.3% of yeiled and a specific activity of 343.1 U mg-1. The molecular weight of the purified Lac 37 II was estimated to be approximately 56 kDa in 12% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The optimal pH and temperature for the protein was 2.7 and 60°C, respectively. The purified Lac 37 II showed higher resistance to all tested metal ions and organic solvents except for Fe2+ and Cd2+ at 37°C and the activity of the purified Lac 37 was significantly enhanced by Cu2+ at 50 mM. The K cat , K m , and K cat /K m of Lac 37 II were 2.977 s-1, 16.1 μM, and 184.9 s-1 μM-1, respecively, in the condition of pH 2.7 and 60°C using ABTS as a substrate. Peptide-mass fingerprinting analysis showed that the Lac 37 II matched to the gene-deduced sequences of lcc3 in T. trogii BAFC 463, other than Lcc1, Lcc 2, and Lcc 4. Compared with laccase prepared at 28°C, the onset of thermo-activation of Lac 37 II activity occurred at 30°C with an increase of 10%, and reached its maximum at the temperatures range of 40-60°C with an increase of about 40% of their original activity. Furthermore, Lac 37 II showed the efficient decolorization ability toward triphenylmethane dyes at 60°C, with decolorization rates of 100 and 99.1% for 25 mg L-1 malachite and crystal violet in 5 h, respectively, when hydroxybenzotriazole (HBT) was used as a mediator. In conclusion, it is the first time to report a thermo-activation laccase from a thermophilic T. trogii strain, which has a better enzyme property and higher decolorization ability among fungal laccases, and it also has a further application prospective in the field of biotechnology.

Two laccase-encoding genes from the marine-derived fungus Pestalotiopsis sp. have been cloned in Aspergillus niger for heterologous production, and the recombinant enzymes have been characterized to study their physicochemical properties, their ability to decolorize textile dyes for potential biotechnological applications, and their activity in the presence of sea salt. The optimal pH and temperature of PsLac1 and PsLac2 differed in relation to the substrates tested, and both enzymes were shown to be extremely stable at temperatures up to 50 &deg, C, retaining 100% activity after 3 h at 50 &deg, C. Both enzymes were stable between pH 4&ndash, 6. Different substrate specificities were exhibited, and the lowest Km and highest catalytic efficiency values were obtained against syringaldazine and 2,6-dimethoxyphenol (DMP) for PsLac1 and PsLac2, respectively. The industrially important dyes&mdash, Acid Yellow, Bromo Cresol Purple, Nitrosulfonazo III, and Reactive Black 5&mdash, were more efficiently decolorized by PsLac1 in the presence of the redox mediator 1-hydroxybenzotriazole (HBT). Activities were compared in saline conditions, and PsLac2 seemed more adapted to the presence of sea salt than PsLac1. The overall surface charges of the predicted PsLac three-dimensional models showed large negatively charged surfaces for PsLac2, as found in proteins for marine organisms, and more balanced solvent exposed charges for PsLac1, as seen in proteins from terrestrial organisms.

Enzyme catalyzed coupling with redox mediators are considered as great interesting and viable technologies to transform antibiotics. This work demonstrated the horseradish peroxidase (HRP) was effective in transforming sulfadiazine (SDZ) transformation coupled with 1-hydroxybenzotriazole (HBT) at varying conditions. The removal of SDZ was independent of Na+ and its ionic strength, but Ca2+ could enhance transformation efficiency by increasing the enzyme activity of HRP. The presence of humic acid (HA) and polystyrene (PS) microplastics showed inhibition on the transformation of SDZ, and the transformation rate constants (k) decreased with the concentration of HA and PS particles increased. These primarily attributed to covalent coupling and electrostatic interaction between SDZ and HA, SDZ and PS, respectively, which reduced the concentration of free SDZ in the reaction solution. The presence of cation recovered the inhibition of SDZ transformation by HA and PS particles, which ascribed to compete between cation and SDZ. The divalent cations (Ca2+) showed more substantial competitiveness than mono (Na+) due to more carried charge. Eight possible transformation products were identified, and potential SDZ transformation pathways were proposed, which include δ-cleavage, γ-cleavage, carbonylation, hydroxylation, SO2 extrusion and SO3 extrusion. In addition, HA and PS particles couldn't affect the transformation pathways of SDZ. These findings provide novel understandings of the transformation and the fate of antibiotics in the natural environment by HRP coupled with redox mediators.

Peptide nanofibers decorated with palladium nanoparticles catalyzed direct coupling of aryl halides with hydroxybenzotriazole to afford the corresponding biaryls in good to excellent yields. The coupling reactions proceeded under simple, green, and mild conditions. The peptide nanofibers were used as recyclable supports in the coupling reactions. This approach is the first to use hydroxybenzotriazole as a phenylating agent.

This work presents chemical functionalization of multi-walled carbon nanotubes (MWCNTs) through chemical modifications. Antibacterial conjugated MWCNTs were synthesized involving the sequential steps of carboxylation. Formation of the active intermediates using hydroxybenzotriazole (HOBt) was done in order to achieve conjugated 2-mercaptobenzimidazole (MWCNT-h) as the final compound. The modification of MWCNTs with antibacterial drug was checked by Fourier transform infrared spectroscopy, Raman spectroscopy, and thermogravimetric analysis. Size and surface characteristics of chemically modified MWCNTs were monitored by scanning electron microscopy and atomic force microscope. Minimal inhibitory concentration (MIC) and antimicrobial activity of functionalized and carboxyl MWCNTs were studied on two gram-negative bacteria as well as one gram-positive bacteria. The MIC results show that functionalized MWCNTs with antibacterial drugs have more effective results than single drug and carboxyl MWCNTs individually against all studied bacteria.

A method to graft gallic acid (GA) onto chitosan (CS) with the assistance of 1-ethyl-3-(3′-dimethylaminopropyl) carbodiimide (EDC) and hydroxybenzotriazole has been previously developed, affording GA-grafted-CS (GA- g -CS). In the present study, the optimal reaction conditions for the synthesis of GA- g -CS with highest gallic acid substitution were determined as chitosan 10.1 mg/mL, mole ratio of gallic acid to EDC fixed at 1, and temperature ranging from 15 to 30 °C. The amount of gallic acid grafted onto chitosan had considerable influence on viscosity of GA- g -CS. Viscosity of GA- g -CS had shear-thinning behavior, and had concentration, temperature and pH-dependent manner. Free gallic acid and NaCl showed little impact on GA- g -CS viscosity, while CaCl 2 and Na 2 SO 4 aggregated GA- g -CS and decreased the viscosity rapidly. GA- g -CS with MgSO 4 exhibited a three-region (shear thinning - plateau or shear thickening - shear thinning) viscosity profile. GA- g -CS shared similar rheological properties with chitosan, but the grafting of gallic acid endowed the polymer with some properties different from plain chitosan. The grafting of gallic acid altered macromolecular structure and provided more possibility for the polymer to interact with environment. GA- g -CS, a chitosan derivative, is a potential material in food industry.

A new analogue of the proline derived organocatalyst ‘pyrrolidine-HOBt’ has been designed and synthesized from l -prolinol and hydroxybenzotriazole (HOBt) employing a simple reaction protocol. The catalyst was found to be effective in promoting the asymmetric Michael addition of cyclohexanone to nitroolefins using water as the reaction medium. The reaction products γ-nitrocarbonyls are obtained in good yields and stereoselectivities.

Several new 1,1′-bis(sulfonyl)ferrocenes designed for the synthesis of sulfonamide linked biological conjugates have been prepared. 1,1′-Bis(sulfonylbromide)ferrocene can be produced from the corresponding sulfonylchloride via a bis(sulfonylhydrazide) intermediate. Bis(sulfonyl-N-hydroxybenzotriazole)ferrocene can also be synthesized from the sulfonyl chloride, and reaction of glycine methyl ester with the sulfonyl chloride affords a [3]ferrocenophane complex. All new compounds have been structurally characterized by X-ray crystallography.

A 1-hydroxybenzotriazole-assisted, N-heterocyclic carbene catalyzed direct β-functionalization of saturated carboxylic esters is disclosed. This formal [3 + 2] annulation reaction of carboxylic esters with isatins affords optically pure spirooxindole lactones (on gram scale) bearing two vicinal stereogenic centers. A dual role of HOBt is proposed based on controlled experiments to rationalize the enhancement of diastereoselectivity and enantioselectivity.

Compounds containing 1,3,4-thiadiazole nucleus appear to be potential tyrosine kinase inhibitors. Previous reports showed that some 1,3,4-thiadiazole derivatives were designed as probable tyrosine kinase inhibitors. Thiol derivative (2) was obtained from the reaction of 5-amino-1,3,4-thiadiazole-2-thiol with 4-fluorophenylacetic acid, ethyldimethyaminopropylcarbodiimide and hydroxybenzotriazole. Subsequent reaction of the obtained thiol derivative with diverse benzyl chlorides afforded the final compounds 3a-3l in a click reaction surprisingly. Derivatives with electron withdrawing moieties (F, Cl) exerted higher yield compared to methoxylated derivatives as electron donating group. Besides, docking studies using ArgusLab 4.0 was done for exploring the probable binding mode and interactions. Investigation of cytotoxicity of target compounds (3a-3l) by MTT assay revealed that these derivatives are more active against the breast cancer cell line MCF-7 and most of these were found to be more effective than imatinib as reference drug. Chlorine containing derivatives at ortho and meta positions were the most cytotoxic in these series.

Cortienic acid was obtained by periodic acid oxidation of fluocinolone acetonide, whereas corresponding amide was synthesized from the cortienic acid and ethyl ester of b-alanine by dicyclohexylcarbodiimide - hydroxybenzotriazole coupling procedure. Lipophilicity of the amide was evaluated by using reversed-phase thin-layer chromatography systems, consisting of ethanol and water in various ratios, and was higher in comparison to fluocinolone acetonide and cortienic acid.

Hydroxybenzotriazole (HOBt) and HOBt-derived reagents have been classified as Class I explosives, with restrictions on their transportation and storage. We explored a range of benzoylated oxime-based reagents as alternatives to benzoyloxybenzotriazole (BBTZ) for the selective benzoylation of carbohydrate polyols. Benzoylated oximes derived from 2-hydroximino-malononitrile, ethyl 2-hydroximino-2-cyanoacetate (Oxyma), and tert-butyl 2-hydroximino-2-cyanoacetate were most effective for benzoylation of a simple primary alcohol, with yields approaching that obtained for BBTZ. When applied to carbohydrate diols, the most effective reagent was identified as benzoyl-Oxyma. Benzoyl-Oxyma is a highly crystalline, readily prepared alternative to BBTZ, useful in the selective benzoylation of carbohydrate polyols.

The title compound tert-butyl 4-(5-(3-fluorophenyl)-1,2,4-oxadiazol-3-yl)piperazine-1-carboxylate was synthesized by condensation reaction between carbamimide and 3-fluorobenzoic acid in the presence of 3-(3-dimethylaminopropyl)carbodiimide hydrochloride and hydroxybenzotriazole under basic condition. It was characterized by spectroscopic evidences such as LCMS, 1H NMR, 13C NMR, IR, and CHN elemental analysis. The structure was further confirmed by single crystal XRD data. The title compound, C17H21FN4O3, crystallized in the monoclinic crystal system and P21/c space group with the unit cell parameters a = 14.281(3) A, b = 11.579(2) A, c = 11.331(2) A, β = 110.674(6)°, Z = 4, and V = 1753.0(6) A3. In the structure, the molecules are linked through weak C‒H···O intermolecular interactions along [010], and aromatic π–π stacking interactions (centroid-centroid distance = 3.7456(15)A generate a three-dimensional architecture. The compound was screened for its in vitro antibacterial and anthelmintic activity. T...

Solid-phase synthesis of antibacterial cyclohexapeptides including wollamides A, B and desotamide B has been developed. Briefly, the protected linear hexapeptides were assembled on 2-chlorotrityl chloride resin using standard Fmoc chemistry and diisopropylcarbodiimide/hydroxybenzotriazole coupling reagents, cleaved off-resin with hexafluoroisopropanol/dichloromethane to keep side-chain protecting groups intact, and cyclized in solution. Final global removal of all protecting groups using a cocktail of trifluoroacetic acid/triisopropylsilane/dichloromethane afforded the desired cyclic hexapeptides, which were characterized by 1H, 13C NMR, and HRMS. Subsequent investigation of macrocyclization parameters such as terminal residues, coupling reagents, and cyclization concentration revealed the optimized conditions for the synthesis of this class of cyclic hexapeptides.

Background: Studies on anti-inflammatory and antimicrobial agents remains a challenging and important area in medicinal chemistry research due to more toxic and rapid development of resistance against first effective drugs. In search of novel anti-inflammatory and antimicrobials agents, bisthiourea derivatives of dipeptide conjugated to 6-fluoro-3- (piperidin-4-yl)benzo[d]isoxazole were synthesized. Methods: The peptides were synthesized by solution phase method and conjugated to 6- fluoro-3-(piperidin-4-yl)benzo[d]isoxazole using 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide (EDCI)/hydroxybenzotriazole (HOBt) as a coupling agent and N-methylmorpholine (NMM) as a base. The protecting group, 2-chlorobenzyloxycarbonyl (2-ClZ) and tertbutyloxycarbonyl (Boc) were deblocked and further reacted with substituted phenyl isothiocyanates to obtain bisthiourea derivatives. Results: The molecules 1-24 were examined for their in vitro anti-inflammatory activity by employing human erythrocyte suspension test and it was found that the IC50 values of 9, 12, 21 and 24 were lower than the IC50 of standard references indomethacin and ibuprofen. Further, all the molecules were also evaluated for their in vitro antibacterial and antifungal activities against various pathogens of human origin by agar well diffusion method. In addition, binding interaction of active molecules (7-12 and 19-24) was performed on active site of cyclooxygenase-2 (COX-2) and Staphylococcus aureus (SA) TyrRS showing good binding profile. Conclusion: Molecular docking result, along with the biological assay data, revealed that the compounds containing electron withdrawing group (F) on phenyl ring of thiourea moiety were potential anti-inflammatory and antimicrobial agents.

The aim of this study was to investigate the antioxidant activities of chitosan acetate (CS-acetate), chitosan hydroxybenzotriazole (CS-HOBt), chitosan thiamine pyrophosphate (CS-TPP) and chitosan ethylenediaminetetraacetic acid (CS-EDTA) nanofiber mats. Chitosan was dissolved with hydroxybenzotriazole (HOBt), thiamine pyrophosphate (TPP) and ethylenediaminetetraacetic acid (EDTA) in distilled water. These chitosan aqueous salts were blended with polyvinyl alcohol (PVA) at volume ratio 30/70 chitosan salts/PVA and prepared to nanofibers via electrospinning process. The morphology of electrospun chitosan aqueous salts based nanofiber mats were observed under scanning electron microscope (SEM). The antioxidant activities were determined employing various established in vitro system such as superoxide, hydroxyl radicals scavenging and metal ion chelating compared with pure PVA nanofiber mats. The results exhibited that the electrospun chitosan aqueous salts based nanofiber mats showed the different antioxidant activity depended on salt forms. Among the salt forms, CS-acetate nanofiber mats showed the highest superoxide radical scavenging effect while CS-HOBt nanofiber mats (IC50 = 7.53 mg/mL) showed the highest hydroxyl radical scavenging effect. For the metal ion chelating activity, CS-EDTA nanofiber mats showed the highest chelating activity (IC50 = 1.07 mg/mL). In summary, the antioxidant chitosan aqueous salt based nanofiber mats have potential for use in pharmaceutical applications.

A novel water soluble Chitosan derivative N-propylphosphonic Chitosan (NPPCS) having a terminal phosphonic acid group was synthesized by reacting Chitosan with Hydroxybenzotriazole (HOBt) and propylphosphonic anhydride (T3P)® via one pot reaction. The novel derivative was characterized by 1H NMR, Attenuated Total Reflectance Infra Red (ATR-IR) spectroscopy and XRD. Due to insolubility of NPPCS in organic solvents, a new process was demonstrated for blending of NPPCS with Polysulfone. The proper blending of NPPCS with Polysulfone was confirmed by ATR-IR spectroscopy. The improved hydrophilicity of PSf/NPPCS membranes was confirmed by contact angle measurement. The permeation studies showed increased flux of PSf/NPPCS membranes as compared to the pristine Polysulfone membrane. The antifouling property of PSf/NPPCS membrane was determined by Bovine Serum Albumin (BSA) protein rejection studies. The membranes showed the enhanced antifouling property as compared to pristine Polysulfone membranes with a maximum of 74% flux recovery ratio (FRR) value.

Gallic acid-grafted-chitosan (GA-g-CS) was synthesized in the presence of 1-ethyl-3-(3'-dimethylaminopropyl) carbodiimide and hydroxybenzotriazole under room temperature. To develop a kind of newly functional film, CS, gelatin, glycerol and Tween 20 were utilized to prepare CS-based composite films with incorporated GA (GA-CS) or conjugated GA (GA-g-CS), and the films were characterized in aspects of physical and functional properties, as well as microstructures. With the increasing of GA concentration, there was a reduction in transmittance, elongation at break and water vapor permeability (WVP) for GA-CS film. For GA-CS films, the higher tensile strength and lower WVP could be obtained when GA was evenly distributed across the films. Different from the GA-CS films, water solubility, swelling ratio, water vapor permeability and scavenging activities on 2,2-Diphenyl-1-picrylhydrazyl/2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) radicals were enhanced for GA-g-CS films, which could be ascribed to the rough surface morphology. The GA-g-CS films exhibited enhanced water vapor permeability when the substitution degree of GA increased. Also, the antimicrobial activities of GA-g-CS films were superior to those of GA-CS films. Our present work developed a way to prepare GA-g-CS films that owned many desirable properties and could be explored as promising biomaterials in food packaging.

The oxidative cleavage of the dihydropyran ring of 1-aryl-isochroman derivatives was carried out for the first time under green chemistry conditions in the presence of the Trametes villosa laccase/1-hydroxybenzotriazole system in buffered water/1,4-dioxane and buffered water/dimethyl carbonate as reaction media. The corresponding oxidation products [2-(2-hydroxyethyl)benzophenone derivatives] were obtained in different yields depending on the substituents on phenyl and isochroman rings. These compounds are useful intermediates for the synthesis of anticancer agents and neuroprotective drugs.

The reaction of thioamino acids and N-terminal peptides, mediated by hindered isonitriles and hydroxybenzotriazole, gives rise to peptide bonds. In one pathway, oxytocin was synthesized by eight such reiterative amidations. In another stereospecific track, oxytocin was constructed by native chemical ligation, wherein the two building blocks were assembled by thioacid amine amidation. The NMR spectra of oxytocin and dihydrooxytocin suggest a high level of preorganization in the latter, perhaps favoring oxidative folding.