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An efficient solvent-free catalyst system for hydrosilylation of aldehydes and ketones was developed based on iron pre-catalyst Fe2(CO)9/C6H4-o-(NCH2PPh2)2BH. The reactions were tolerant of many functional groups and the corresponding alcohols were isolated in good to excellent yields following basic hydrolysis of the reaction products. The reaction is likely catalyzed by an in situ generated pincer ligated iron hydride complex.

6″-[18 F]fluoromaltotriose is a positron emission tomography tracer that can differentiate between bacterial infection and inflammation in vivo. Bacteria-specific uptake of 6″-[18 F]fluoromaltotriose is attributed to the targeting of maltodextrin transporter in bacteria that is absent in mammalian cells. Herein, we report a new synthesis of 6″-[18 F]fluoromaltotriose as a key step for its clinical translation. In comparison with the previously reported synthesis, the new synthesis features unambiguous assignment of the fluorine-18 position on the maltotriose unit. The new method utilizes direct fluorination of 2″,3″,4″-tri-O-acetyl-6″-O-trifyl-α-D-glucopyranosyl-(1-4)-O-2',3',6'-tri-O-acetyl-α-D-glucopyranosyl-(1-4)-1,2,3,6-tetra-O-acetyl-D-glucopyranose followed by basic hydrolysis. Radiolabeling of the new maltotriose triflate precursor proceeds using a single HPLC purification step, which results in shorter reaction time in comparison with the previously reported synthesis. Successful synthesis of 6″-[18 F]fluoromaltotriose has been achieved in 3.5 ± 0.3% radiochemical yield (decay corrected, n = 7) and radiochemical purity above 95%. The efficient radiosynthesis of 6″-[18 F]fluoromaltotriose would be critical in advancing this positron emission tomography tracer into clinical trials for imaging bacterial infections.

Four new chromones, phomochromenones D–G (1–4), along with four known analogues, diaporchromone A (5), diaporchromanone C (6), diaporchromanone D (7), and phomochromenone C (8), were isolated from the culture of Phomopsis asparagi DHS-48 from Chinese mangrove Rhizophora mangle. Their structures were elucidated on the basis of comprehensive spectroscopic analysis. The absolute configurations of 1 and 4 were assigned on the basis of experimental and calculated electronic circular dichroism (ECD) data, and those of enantiomers 2 and 3 were determined by a modified Mosher’s method and basic hydrolysis. To the best of our knowledge, phomochromenones D–F (1–4) possessing a 3-substituted-chroman-4-one skeleton are rarely found in natural sources. Diaporchromone A (5) showed moderate to weak immunosuppressive activity against T and/or B lymphocyte cells with IC50 of 34 μM and 117 μM.

The mosquito-borne viruses belonging to the genus Flavivirus such as Dengue virus (DENV) and Zika virus (ZIKV) cause human infections ranging from mild flu-like symptoms to hemorrhagic fevers, hepatitis, and neuropathies. To date, there are vaccines only for few flaviviruses while no effective treatments are available. Pyridobenzothiazole (PBTZ) derivatives are a class of compounds endowed with a promising broad-spectrum anti-flavivirus activity and most of them have been reported as potent inhibitors of the flaviviral NS5 polymerase. However, synthesis of PBTZ analogues entails a high number of purification steps, the use of hazardous reagents and environmentally unsustainable generation of waste. Considering the promising antiviral activity of PBTZ analogues which require further exploration, in this work, we report the development of a new and sustainable three-component reaction (3CR) that can be combined with a basic hydrolysis in a one-pot procedure to obtain the PBTZ scaffold, thus reducing the number of synthetic steps, improving yields and saving time. 3CR was significantly explored in order to demonstrate its wide scope by using different starting materials. In addition, taking advantage of these procedures, we next designed and synthesized a new set of PBTZ analogues that were tested as anti-DENV-2 and anti-ZIKV agents. Compound 22 inhibited DENV-2 NS5 polymerase with an IC50 of 10.4 μM and represented the best anti-flavivirus compound of the new series by inhibiting DENV-2- and ZIKV-infected cells with EC50 values of 1.2 and 5.0 μM, respectively, that translates into attractive selectivity indexes (SI - 83 and 20, respectively). These results strongly reaffirm PBTZ derivatives as promising anti-flavivirus agents that now can be synthesized through a convenient and sustainable 3CR in order to obtain more potent compounds for further pre-clinical development studies.

The aim of this study was to develop a positron emission tomography (PET) tracer to visualize and monitor therapeutic response to bacterial infections. In our continued efforts to find maltose based PET tracers that can image bacterial infections, we have designed and prepared 6''-[18 F]fluoromaltotriose as a second generation PET imaging tracer targeting the maltodextrin transporter of bacteria. We have developed methods to synthesize 6''-deoxy-6''-[18 F]fluoro-α-D-glucopyranosyl-(1-4)-O-α-D-glucopyranosyl-(1-4)-O-D-glucopyranose (6''-[18 F]-fluoromaltotriose) as a bacterial infection PET imaging agent. 6''-[18 F]fluoromaltotriose was prepared from precursor, 2'',3'',4''-tri-O-acetyl-6''-O-nosyl-α-D-glucopyranosyl-(1-4)-O-2',3',6'-tri-O-acetyl-α-D-glucopyranosyl-(1-4)-1,2,3,6-tetra-O-acetyl-D-glucopyranose (per-O-acetyl-6''-O-nosyl-maltotriose 4). This method utilizes the reaction between precursor 4 and anhydrous [18 F]KF/Kryptofix 2.2.2 in dimethylformamide (DMF) at 85°C for 10 minutes to yield per-O-acetyl-6''-deoxy-6-'' [18 F]-fluoromaltotriose (7). Successive acidic and basic hydrolysis of the acetyl protecting groups in 7 produced 6''-[18 F]fluoromaltotriose (8). Also, cold 6''- [19 F]fluoromaltotriose was prepared from per-O-acetyl-6''-hydroxymaltotriose via a diethylaminosulfur trifluoride reaction followed by a basic hydrolysis. A successful synthesis of 6''-[18 F]-fluoromaltotriose has been accomplished in 8 ± 1.2% radiochemical yield (decay corrected). Total synthesis time was 120 minutes. Serum stability of 6''-[18 F]fluoromaltotriose at 37°C indicated that 6''-[18 F]-fluoromaltotriose remained intact up to 2 hours. In conclusion, we have successfully synthesized 6''-[18 F]-fluoromaltotriose via direct fluorination of an appropriate precursor of a protected maltotriose.

The simultaneous identification and quantification of target metabolites from herbal medicines are difficult to implement by the full-scan MS based nontargeted metabolomics approaches. Here an in-source multiple collision-neutral loss filtering (IMC-NLF) based nontargeted metabolomics approach is developed and applied to identify and quantify the variations of malonyl-ginsenosides, a common group of acyl saponins with potential anti-diabetic activity, among Panax ginseng, P. quinquefolius, and P. notoginseng. The key steps of the IMC-NLF strategy are the acquisition of specific high-resolution neutral loss data and the efficient filtering of target precursor ions from the full-scan spectra. Using a hybrid LTQ-Orbitrap mass spectrometer after UHPLC separation, abundant in-source product ions, [M-H-CO2]- (due to the vulnerability of the carboxyl group) and [M-H-Mal.]-, were generated at the energies of 70 V and 90 V, respectively. After spectral deconvolution, the generated peak list was screened by dual NLF using a Neutral Loss MS Finder software (NL of 43.9898 Da for CO2 and 86.0004 Da for the malonyl substituent). By combining the precursor ions list-triggered HCD-MS/MS and basic hydrolysis, a total of 101 malonyl-ginsenosides (including 69 from P. ginseng, 52 from P. quinquefolius, and 44 from P. notoginseng) were identified or tentatively characterized. The variations of 81 characterized malonyl-ginsenosides among 45 batches of Ginseng samples were statistically analyzed disclosing ten potential markers. It is the first systematic analysis of malonyl-ginsenosides. The IMC-NLF approach by a single analytical platform is promising in targeted analyses of modification-specific metabolites in metabolomics and drug metabolism.

A new strategy for the protection of amines has been developed involving reaction with pyridil under the influence of N-heterocyclic carbene catalysis. The methodology is capable of distinguishing between two amines characterised by small differences in steric bulk and the resulting pyridoyl amides can be cleaved without requiring either strongly acidic or basic hydrolysis.

Extraction of free and bound phenols from millet in acidic and basic hydrolytic conditions were compared for the first time. Acidic hydrolysis was able to extract the highest amount of total phenolic compounds (up to 178 mg/100 g) while the basic hydrolysis underestimates the phenolic concentration. Our findings pointed out for the first time that methyl ferulate is naturally present as bound phenol in millet. Response Surface Methodology was then applied to both acidic and basic hydrolytic extractive conditions: the acidic procedure, optimized in terms of extractive time and temperature and concentration of the acidic mean, gave the best results, allowing definition of Method Operable Design Region and quantitation of the total amount of phenols in millet samples in a single extractive step. This optimized method is suitable for further accurate investigations of the typical phenols of the numerous varieties of this recently re-discovered minor cereal.

A series of four different low molecular weight gellan gum products was obtained by alkaline hydrolysis with the aim to investigate the impact of the molecular weight on the rheological properties of the polysaccharide aqueous dispersions and on the physicochemical characteristics of derived ionotropic crosslinked hydrogels. In particular, thermo-rheological analysis was conducted on aqueous dispersions to study the influence of molecular weight on the thermogelation properties typical of the native polysaccharide while strain sweep experiments were conducted to establish if aqueous dispersion shows a viscoelastic behavior. The effect of different Ca2+ on the rheological properties of hydrogels were studied. Furthermore, ionotropic crosslinked hydrogels were analyzed in terms of morphology on the dried state and swelling behavior, while their viscoelastic properties were studied by means of rheological analysis conducted in frequency sweep regime after different time points of incubation in phosphate buffer at pH 7.4. Release experiments conducted using fluorescein isothiocyanate labelled dextran as a model diffusion agent and was performed to investigate the possibility of using the low molecular weight GG-derived hydrogels as an active molecule-releasing device. Finally, the cytocompatibility of hydrolysis products was investigated, as well as the capacity of hydrogels to encapsulate viable MC3T3-E1 preosteoblastic cells.

Using the Leuckart–Wallach reaction, novel conformationally flexible structural analogs of Bromantane drug have been synthesized from 3-haloadamantane-1-carbaldehydes. Basic hydrolysis of the prepared compounds has been studied as a model of one of the pathways of their transformations in vivo.

The kinetics of basic hydrolysis of crystal violet (CV) in CTAB/KBr/C9OH micellar media was investigated under pseudo-first-order conditions. The reaction was monitored spectrophotometrical...

The cycloadducts 9,10-bis(trifluoromethyl)benzobarrelenes were prepared by the reaction of hexafluorobut-2-yne (HFB) with 1- and, 2- substituted naphthalenes in moderate to high yields. In most cases the reaction proceeds with the formation of two isomeric products derived from cycloaddition of HFB to different aromatic rings of the naphthalene system. The individual isomers were isolated by column chromatography and fully characterized. The basic hydrolysis of ester derivatives of the various 9,10-bis(trifluoromethyl)benzobarrelenes provided the corresponding acids.

The treatment of hexahydro-1.3-pentalenedimethanol 1 with MCPB acid gave a pentalenofurane compound 7 instead of an epoxide, in >90% yield by participation of the closer hydroxymethyl group in epoxidation. Acyl-protected derivatives 1a–1e gave a mixture of exo- and endo-epoxides 5/6 as expected, with exo-epoxides representing the major compound in all cases. The best yield for exo-epoxide was obtained for diacetate 1a. Basic hydrolysis of exo-epoxides gave the pentalenofurane compound 7, while that of the endo-epoxide 6c gave the unsubstituted endo-epoxide 6. The structure of the compounds was confirmed by IR, MS, 1H and 13C NMR spectra and also by extensive X-ray crystallography of compounds 7c, 7d, 5a, 6c and 7.

Dye-sensitized solar cells are attracted much interest in the fields of clean energy. In this work, a novel ruthenium terpyridine dimeric complex (N749 dimer) was designed and synthesized through the coordination of 4,4',4"-tricarboxy-2,2':6',2"-terpyridine with ruthenium trichloride, bridging with 4,4'-bipyridine and basic hydrolysis. The calculated and experimental UV-vis absorption spectrums for N749 dimer were compared to those of the commercial black dye N749. The results showed that N749 dimer exhibits wider spectrum absorption range and higher molar extinction coefficient. Dye sensitized solar cells were fabricated based on the N749 dimer. The cell efficiency could reach 2.9% battery efficiency under simulated sunlight irradiation of 100 mW/cm2 power AM1.5G ruthenium. The results provide a new direction for designing the ruthenium dyes.

Two new analogs of bestatin were prepared from D-leucine and D-valine in a stereoselective and efficient way. An amino- peptidase inhibitor bestatin shows significant biological effects on immunomodulation and is marketed for the treatment of acute myelocytic leukemia. The key intermediates, trans-oxazolidine methyl esters 2a and 2b, were obtained with more than 20 to 1 stereoselectivity in a one-pot procedure by the three cascade reactions between N-hydroxymethyl protected α-amino aldehydes (4a and 4b) and phenylsulfonylnitromethane (PhSO2CH2NO2) and the following in-situ ozonolysis. Basic hydrolysis of 2a and 2b, and then the peptide coupling with L-Leu-OMe produced the protected derivatives of two new bestatin analogs, 3a and 3b, respectively. The new isobutyl and isopropyl analogs of bestatin (1a and 1b) were produced in overall 51% and 38% yields, respectively, with high stereoselectivity from the corresponding protected α-amino aldehydes 4 in a six-step process.

The aim of this study was to optimize the content of EPA and DHA in the process of enzymatic acidolysis of canola oil and concentrated of long-chain polyunsaturated fatty acids (LCPUFA) in structured triacylglycerols (TAGs). For this purpose, nonspecific lipase B from Candida antarctica immobilized in a supercritical CO2 was used. Crude salmon oil obtained from the industrial byproducts was used to obtain LCPUFA concentrate. Initially, a LCPUFAs concentrate was obtained by basic hydrolysis and posterior complexation with urea. Subsequently the process variables were optimized enzymatic acidolysis were optimized using a central composite rotational design 25-1 + star, with 5 factors and 30 experimental trials, based on the response surface methodology. The optimal conditions that maximized the content of EPA and DHA to 3.92 g/100 g TFA and 9.09 g/100 g TFA, respectively in the purified TAGs corresponded to a LCPUFA percentage 71.71% and canola oil percentage 28.29%, temperature 57.8 °C, pressure 172.0 bar, time 23.97 h enzyme percentage of 7.74%. El objetivo del presente trabajo fue optimizar el contenido de ácidos grasos EPA y DHA en el proceso de acidólisis enzimática de aceite de canola y concentrado de ácidos grasos poliinsaturados de cadena larga (AGPICL) en triacilglicéridos estructurados (TAGs). Para ello, se empleó lipasa B inespecífica de Candida antarctica inmovilizada en condiciones CO2 supercrítico. El aceite crudo de salmón obtenido a partir de los subproductos industriales se utilizó para obtener concentrados de AGPICL. Como primer paso, se obtuvo un concentrado de AGPICL mediante una hidrolisis básica y posterior complejación con urea. Posteriormente se optimizó las variables del proceso de acidólisis enzimática mediante un diseño compuesto central rotacional 25-1 más estrella, de 5 factores con 30 ensayos experimentales, basado en la metodología superficie respuesta. Las condiciones óptimas que maximizaron el contenido de EPA a 3,92 g/100 g de ácidos grasos totales (AGT) y de DHA a 9,09 g/100 g AGT en los TAGs purificados correspondieron a una relación AGPICL/Canola de 71,71 %, temperatura de 57,8 ºC, presión de 172,0 bar, tiempo de 23,97 h y concentración de enzima de 7,74%.

Basic hydrolysis of a dichloromethane extract of Stevia lucida yielded (4R,5S,7R,9R,10R,11R)-7,9-dihydroxylongipin-2-en-1-one (1), which was oxidized and subjected to acidic conditions to generate the new seco-moreliane derivative 3. The structure of 3 was established based on NMR data interpretation and confirmed computationally. A plausible mechanism for the carbocationic rearrangement of the trione 2 to the seco-moreliane 3 was supported by DFT computations.

espanolSe evaluo el efecto de temperatura y concentracion del hidrolizante en la extraccion de colageno soluble en acido a partir de tres regiones anatomicas de la tilapia roja (Oreochromis spp): escamas, espinas y pieles. Se optimizo el proceso de extraccion aplicando dos disenos experimentales en cada matriz estudiada en las etapas de hidrolisis basica (NaOH) para la liberacion de proteinas del tejido conectivo (PTC) e hidrolisis acida (CH3-COOH) para la obtencion del colageno. Los resultados revelaron que a 25°C y 0.4M de NaOH en la hidrolisis basica, se obtiene la mayor liberacion de PTC en las matrices estudiadas. Ademas, se puede alcanzar el maximo porcentaje de colageno (% Cl) en la hidrolisis acida con una solucion 0,7M de CH3-COOH y temperaturas de 18,5°C, 11,0°C y 21,5°C para piel (0,88%), escamas (2,16%) y espinas (0,51%), respectivamente. EnglishThe effect of temperature and concentration of the hydrolyzing agent on the extraction of acid soluble collagen from three anatomical regions of red tilapia (Oreochromis spp) was evaluated: scales, bones and skin. The extraction process is optimized using two experimental designs in each matrix studied in the stages of basic hydrolysis (NaOH) for the release of connective tissue proteins (CTP) and acid hydrolysis (CH3 COOH) to obtain collagen. Results showed that at 25°C and 0.4M solution of NaOH in the basic hydrolysis the maximum CTP in the studied matrixes are obtained. Also, the optimum condition of collagen extraction by acid hydrolysis can be achieved at 0.7M solution of CH3-COOH and temperatures of 18.5°C, 11.0 °C and 21.5°C for skin (0.88%), scales (2.16%) and spines (0.51%), respectively.

An effective method for the synthesis of N-ethyl-2,1,3-benzoselenadiazolamines 11 and 15 has been described. Modified Gould-Jacobs reaction of N-ethylbenzoselenadiazol-4-amine 15 provided 9-ethylselenadiazoloquinolone derivatives 2 and 19 in high yields. Acid-promoted ring closure of enamine 18c unexpectedly afforded completely deacetylated product - 9- ethylselenadiazoloquinolone 2. Identical product was obtained by ethylation of selenadiazolo(3,4-h)quinolone 1 and by basic hydrolysis of ethyl ester 19b followed by thermal decarboxylation of the corresponding acid 20 .

A Bronsted acid catalyzed bisindolization reaction with suitable α-amido acetals that tolerates a wide range of indoles is reported. The method allows rapid access to the biologically relevant bisindolyl ethanamine scaffold in good to excellent yields upon mild amide basic hydrolysis. In preliminary pharmacological studies, some of these compounds display cytotoxic activity in U937 cancer cells. The marine natural alkaloid 2,2-di(6′-bromo-3′-indolyl)-ethylamine was the most active compound and could be a lead candidate for further optimization. For the first time, the biological role of this brominated bisindole marine alkaloid is presented.

A facile and sensitive fluorescent probe for hydrazine was successfully constructed, displaying excellent colorimetric and ratiometric responses towards hydrazine via Ing–Manske hydrazinolysis conditions in semi-aqueous buffer solution. Semi-empirical calculations as well as spectroscopic results revealed the signalling mechanism of the current probe under hydrazinolysis conditions, in which hydrazine exclusively deprotected the phthalimide group by an intermediate of phthalhydrazide. Extensive screening of pH effects on the probe with the aid of proton nuclear magnetic resonance and mass spectrometry supported the distinctive and diverse ratiometric responses under hydrazinolysis and basic hydrolysis conditions. Time resolved photoluminescence measurements of the probe further confirmed its discernible ratiometric responses probed at respective wavelengths. A distinctive ratiometric response under basic hydrolysis conditions and a successful utilization of probe towards hydrazine detection in living cells are demonstrated.