RESUMEN
A series of novel mandelic acid derivatives containing a 1,3,4-oxadiazothioether moiety were designed and synthesized. Bioassay results showed that some target compounds exhibited certain antifungal activity against six kinds of pathogenic fungi in vitro. Among the compounds, the EC50 values of T41 against Gibberella saubinetii, Verticillium dahlia and Sclerotinia sclerotiorum were 31.0, 27.0 and 32.1 µg/ml, respectively, and the EC50 value of T14 against S. sclerotiorum was 14.7 µg/ml. The antifungal activity against the resistant fungus S. sclerotiorum indicated that this series of target compounds may have the similar action modes or sites as the commercialized succinate dehydrogenase inhibitor carboxin. A morphological study with fluorescence microscope demonstrated that T41 can significantly destroy the membrane integrity of G. saubinetii.
Asunto(s)
Antifúngicos/síntesis química , Ascomicetos/efectos de los fármacos , Ácidos Mandélicos/síntesis química , Sulfuros/química , Antifúngicos/farmacología , Carboxina/química , Dominio Catalítico , Resistencia a Medicamentos , Humanos , Ácidos Mandélicos/farmacología , Unión Proteica , Relación Estructura-Actividad , Succinato Deshidrogenasa/metabolismoRESUMEN
Recently, chiral ionic liquids have attracted increasing attention in analytical chemistry. However, only a few papers focus on the application of them in visual chiral recognition. Herein, two functionalized chiral ionic liquids derived from (S)-mandelic acid (1-butyl-3-methylimidazolium mandelate, CIL1 and N-butyl-N-methylpyrrolidinium mandelate, CIL2) were prepared for visual chiral recognition of aromatic amino acids for the first time. In the presence of Cu(II) and appropriate solvents, visual enantiomeric responses of phenylalanine, tryptophane, tyrosine and phenylglycine were observed. Relying on solubility or color differences, all chiral recognition could be finished within 5 min. The potential mechanism was investigated by means of infrared spectroscopy, ultraviolet spectroscopy, thermal gravity analysis, elemental analysis and scanning electron microscope. Results revealed that CuSO4 interacted with CIL1 and D-tryptophane in the ratio of 1:1.96:0.43 in relevant precipitate, and the different stability of complex was responsible for the chiral recognition. In addition, resolution of racemic tryptophane was performed, which offered excellent enantiomeric excess values (94.2% for CIL1 and 95.1% for CIL2 in solid phase). The proposed ionic liquids had strong enantioselectivity for aromatic amino acids and great potential in visual chiral recognition.
Asunto(s)
Aminoácidos Aromáticos/análisis , Líquidos Iónicos/química , Ácidos Mandélicos/química , Líquidos Iónicos/síntesis química , Ácidos Mandélicos/síntesis química , Estructura Molecular , EstereoisomerismoRESUMEN
Eight organotin(IV) complexes (C1-C8) have been synthesized and characterized by elemental analysis, fourier transform infrared spectroscopy (FT-IR), multinuclear nuclear magnetic resonance (1H, 13C and 119Sn NMR), high resolution mass spectroscopy (HRMS) and single crystal X-ray structural analysis. Crystallographic data show that C1 was a tetranuclear 16-membered macrocycle complex, C2-C4 and C7 were centrosymmetric dimer distannoxane and there was a Sn2O2 four-membered ring in the middle of the molecule, respectively, C5 and C6 are monoorganotin complexes due to the dehydroalkylation effect during the reaction, while C8 forms a one-dimensional chain structure. The cytotoxicity of all complexes were tested by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assays against three human tumor cell lines NCI-H460, MCF-7 and HepG2. The dibutyltin complex C2 has been shown to be more potent antitumor agents than other complexes and carboplatin. Cell apoptosis study of C2 with the high activity on HepG2 and MCF-7 cancer cell lines was investigated by flow cytometry, it was shown that the antitumor activity of C2 was related to apoptosis, but it has different cell cycle arrest characteristics from platinum compounds, and the proliferation was inhibited by blocking cells in S phase. The DNA binding activity of the C2 was studied by UV-visible absorption spectrometry, fluorescence competitive, viscosity measurements and gel electrophoresis, results shown C2 can be well embedded in the double helix of DNA and cleave DNA.
Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Complejos de Coordinación/farmacología , ADN de Neoplasias/efectos de los fármacos , Glioxilatos/farmacología , Ácidos Mandélicos/farmacología , Compuestos Orgánicos de Estaño/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Glioxilatos/síntesis química , Glioxilatos/química , Humanos , Ácidos Mandélicos/síntesis química , Ácidos Mandélicos/química , Simulación del Acoplamiento Molecular , Estructura Molecular , Compuestos Orgánicos de Estaño/síntesis química , Compuestos Orgánicos de Estaño/química , Relación Estructura-ActividadRESUMEN
Dying cell clearance is critical for myriad biological processes such as tissue homeostasis. We herein report an enzyme-activated fluorescence cell labeling approach and its use for multicolor imaging of dying cell clearance. Diacetylated 4-hydroxymandelic acid (DHA)-conjugated dyes give rise to reactive quinone methides upon deacetylation in live cells, which in turn covalently labels cellular proteins. With partner cells tagged with distinct fluorescence, apoptotic cell clearance by Raw 264.7 macrophages and epithelial HeLa cells was captured by confocal microscopy, showing the potential of DHA-based cell labeling for investigating cell-cell interactions.
Asunto(s)
Apoptosis , Colorantes Fluorescentes/química , Ácidos Mandélicos/química , Necrosis , Animales , Bovinos , Línea Celular Tumoral , Cumarinas/síntesis química , Cumarinas/química , Cumarinas/toxicidad , Esterasas/química , Fluoresceínas/síntesis química , Fluoresceínas/química , Fluoresceínas/toxicidad , Fluorescencia , Colorantes Fluorescentes/síntesis química , Colorantes Fluorescentes/toxicidad , Humanos , Ácidos Mandélicos/síntesis química , Ácidos Mandélicos/toxicidad , Ratones , Microscopía Confocal/métodos , Microscopía Fluorescente/métodos , Prueba de Estudio Conceptual , Células RAW 264.7 , Rodaminas/síntesis química , Rodaminas/química , Rodaminas/toxicidad , Coloración y Etiquetado/métodos , PorcinosRESUMEN
We report a Rh-catalyzed hydroamination of 1,3-dienes to generate homoallylic amines. Our work showcases the first case of anti-Markovnikov selectivity in the intermolecular coupling of amines and 1,3-dienes. By tuning the ligand properties and Brønsted acid additive, we find that a combination of rac-BINAP and mandelic acid is critical for achieving anti-Markovnikov selectivity.
Asunto(s)
Compuestos Alílicos/síntesis química , Aminas/síntesis química , Alquenos/síntesis química , Alquenos/química , Compuestos Alílicos/química , Aminación , Aminas/química , Catálisis , Ligandos , Ácidos Mandélicos/síntesis química , Ácidos Mandélicos/química , Naftalenos/síntesis química , Naftalenos/química , Rodio/químicaRESUMEN
Herein, we reported a new strategy based on self-assembly chemistry for chiral discrimination of glucose on a new S-mandelic acid-appended calix[4]arene (S-MC4) modified nanostructure, which exhibits macroscopic chiral preference for d-glucose via contact angle measurements (CA). The proposed macroscopic chiral device displays rapidly remarkable specificity and is convenient to use, which should be suitable for diagnostic purposes, nanomedical applications, etc.
Asunto(s)
Calixarenos/química , Glucosa/química , Calixarenos/síntesis química , Ácidos Mandélicos/síntesis química , Ácidos Mandélicos/química , Modelos Moleculares , Estereoisomerismo , Propiedades de Superficie , HumectabilidadRESUMEN
Novel mandelate ionic liquids with quartenary ammonium cations were synthesized and characterized. The compounds exhibit antimicrobial activity and the most potent one is of similar efficacy against Gram+ bacteria as its counterpart chloride. On the other hand, the mandelates are much less active against Gram-bacteria and fungi. QSAR models suggest that, with respect to cation, their potency depends on lipophilicity. The synthesized ionic liquids are also quite cytotoxic against mammalian cells.
Asunto(s)
Antiinfecciosos/síntesis química , Antiinfecciosos/farmacología , Líquidos Iónicos/química , Líquidos Iónicos/farmacología , Ácidos Mandélicos/síntesis química , Ácidos Mandélicos/farmacología , Cristalografía por Rayos X , Bacterias Grampositivas/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Relación Estructura-Actividad Cuantitativa , SolucionesRESUMEN
Epoxy functionalized magnetic Fe3O4@SiO2 nanoparticles were successfully prepared and characterized by Fourier-transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM). The prepared nanoparticles were used for immobilization of alcohol dehydrogenase (ADH) from Saccharomyces cerevisiae by covalent attachment. The optimal immobilization conditions were obtained as follows: enzyme/support 4.49mg/g, pH 8.0, buffer concentration 0.05M, time 12h and temperature 30°C. Under these conditions, a high immobilization yield and efficiency of above 92% were obtained after the optimization. Broad pH tolerance and high thermostability were achieved by the immobilization. The immobilized ADH retained about 84% initial activity after five cycles. Kinetic parameters Vmax and Km of free and immobilized ADH were determined as 56.72µM/min, 44.27µM/min and 11.54mM, 31.32mM, respectively. (R)-mandelic acid synthesis with the immobilized ADH was carried out, and the yield of (R)-mandelic acid was as high as 64%. These results indicate that the ADH immobilized onto epoxy-functionalized nanoparticles is an efficient and simple way for preparation of stable ADH, and the immobilized ADH has potential applications in the production of (R)-mandelic acid.
Asunto(s)
Alcohol Deshidrogenasa/química , Enzimas Inmovilizadas/química , Proteínas Fúngicas/química , Glioxilatos/química , Nanopartículas de Magnetita/química , Ácidos Mandélicos/química , Ácidos Mandélicos/síntesis química , Alcohol Deshidrogenasa/aislamiento & purificación , Biocatálisis , Tampones (Química) , Estabilidad de Enzimas , Enzimas Inmovilizadas/aislamiento & purificación , Resinas Epoxi/química , Óxido Ferrosoférrico/química , Proteínas Fúngicas/aislamiento & purificación , Concentración de Iones de Hidrógeno , Cinética , Nanopartículas de Magnetita/ultraestructura , Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/enzimología , Dióxido de Silicio/química , Estereoisomerismo , TemperaturaRESUMEN
The concept of deuterium enrichment has gained more attention due to its advantages in the studies of clinical pharmacokinetics and metabolic profiles. In addition, it is cost and time efficient to develop deuterium-enriched drugs. Herein we built a combinatorial library of deuterated (S)-oxybutynins which all 8 D-compounds were characterized by MS, [Formula: see text] NMR and [Formula: see text]C NMR.
Asunto(s)
Deuterio/química , Ácidos Mandélicos/síntesis química , Técnicas Químicas Combinatorias , Ácidos Mandélicos/química , Estructura MolecularRESUMEN
Mandelylthiamin (MTh) is an accurate model of the covalent intermediate derived from the condensation of thiamin diphosphate and benzoylformate in benzoylformate decarboxylase. The properties and catalytic susceptibilities of mandelylthiamin are the subjects of considerable interest. However, the existing synthesis gives only trace amounts of the precursor to MTh as it is conducted under reversible conditions. An improved approach derives from the unique ability of lithium ions to drive to completion the otherwise unfavorable condensation of the conjugate base of thiamin and methyl benzoylformate. The unique efficiency of the condensation reaction in the presence of lithium ions is established in contrast to the effects of other Lewis acids. Interpretation of the pattern of the results indicates that the condensation of the ketone and thiamin is thermodynamically controlled. It is proposed that the addition of lithium ions displaces the equilibrium toward the product through formation of a stable lithium-alkoxide.
Asunto(s)
Cetonas/química , Litio/química , Ácidos Mandélicos/síntesis química , Tiamina/análogos & derivados , Tiamina/química , Técnicas de Química Sintética , Ácidos de Lewis/química , Tiamina/síntesis químicaRESUMEN
An unprecedented rhodium(III)-catalyzed regioselective redox-neutral annulation reaction of 1-naphthylamine N-oxides with diazo compounds was developed to afford various biologically important 1H-benzo[g]indolines. This coupling reaction proceeds under mild reaction conditions and does not require external oxidants. The only by-products are dinitrogen and water. More significantly, this reaction represents the first example of dual functiaonalization of unactivated a primary C(sp(3) )H bond and C(sp(2) )H bond with diazocarbonyl compounds. DFT calculations revealed that an intermediate iminium is most likely involved in the catalytic cycle. Moreover, a rhodium(III)-catalyzed coupling of readily available tertiary aniline N-oxides with α-diazomalonates was also developed under external oxidant-free conditions to access various aminomandelic acid derivatives by an O-atom-transfer reaction.
Asunto(s)
1-Naftilamina/química , Compuestos Azo/química , Hidrógeno/química , Indoles/síntesis química , Óxidos de Nitrógeno/química , Rodio/química , Aminación , Compuestos de Anilina/química , Catálisis , Indoles/química , Malonatos/química , Ácidos Mandélicos/síntesis química , Ácidos Mandélicos/química , Modelos Moleculares , Oxidación-ReducciónRESUMEN
A novel approach towards the synthesis of α-ketoamides using tertiary amines as nitrogen group sources via C-N bond cleavage has been developed. In the presence of Ag2CO3 and K2S2O8, α-keto acids reacted with tertiary amines to afford the corresponding α-ketoamides in good yields.
Asunto(s)
Amidas/síntesis química , Aminas/química , Glioxilatos/química , Ácidos Mandélicos/química , Plata/química , Amidas/química , Aminas/síntesis química , Catálisis , Glioxilatos/síntesis química , Cetonas/síntesis química , Cetonas/química , Ácidos Mandélicos/síntesis químicaRESUMEN
Incorporation reactions of carbon dioxide (CO(2)) with N-Boc-α-amido and α-acetoxy stannanes were developed using CsF as a mild tin activator. Monoprotected α-amido stannanes could be used, and the corresponding arylglycine derivatives were obtained in moderate-to-high yields under 1 MPa (10 atm) of CO(2) pressure. α-Acetoxy stannanes also underwent carboxylation to afford mandelic acid derivatives in excellent yields under ambient CO(2) pressure. Both transformations enabled the synthesis of α-tertiary and α-quaternary carboxylic acid derivatives. In addition, the chirality of (S)-N-tert-butylsulfonyl-α-amido stannanes was transferred with up to 90% inversion of configuration at 100 °C.
Asunto(s)
Dióxido de Carbono/química , Glicina/síntesis química , Ácidos Mandélicos/síntesis química , Compuestos de Estaño/química , Glicina/análogos & derivados , Glicina/química , Ácidos Mandélicos/química , Estructura Molecular , EstereoisomerismoRESUMEN
An efficient and facile process to synthesize mandelic acid through phase transfer catalysis (PTC; also phase transfer catalyst) using ultrasound in an ionic liquid has been developed. Mandelic acid was synthesized from benzaldehyde with chloroform in an 89.6% yield at 60°C for 2h by using tetrabutyl ammonium bromide (TBAB) as a phase transfer catalyst. Effects of different factors, such as frequency of ultrasound, reaction temperature, kinds of PTC and solvents had been investigated to obtain the optimum condition. It was observed that the ultrasonically promoted synthesis of mandelic acid by PTC in the ionic liquid exhibited significant enhancement in reaction yields under ambient conditions.
Asunto(s)
Líquidos Iónicos/química , Líquidos Iónicos/efectos de la radiación , Ácidos Mandélicos/síntesis química , Ácidos Mandélicos/efectos de la radiación , Sonicación/métodos , Catálisis/efectos de la radiación , Dosis de RadiaciónRESUMEN
A nitrilase gene from Alcaligenes sp. ECU0401 was cloned and overexpressed in Escherichia coli BL21 (DE3) in a soluble form. The encoded protein with a His6-tag was purified to nearly homogeneity as revealed by SDS-PAGE with a molecular weight of approximately 38.5 kDa, and the holoenzyme was estimated to be composed of 10 subunits of identical size by size exclusion chromatography. The V(max) and K(m) parameters were determined to be 27.9 µmol min⻹ mg⻹ protein and 21.8 mM, respectively, with mandelonitrile as the substrate. The purified enzyme was highly thermostable with a half life of 155 h at 30 °C and 94 h at 40 °C. Racemic mandelonitrile (50 mM) could be enantioselectively hydrolyzed to (R)-(-)-mandelic acid by the purified nitrilase with an enantiomeric excess of 97%. The extreme stability, high activity and enantioselectivity of this nitrilase provide a solid base for its practical application in the production of (R)-(-)-mandelic acid.
Asunto(s)
Alcaligenes/enzimología , Aminohidrolasas/aislamiento & purificación , Aminohidrolasas/metabolismo , Estabilidad de Enzimas/genética , Ácidos Mandélicos/síntesis química , Acetonitrilos/química , Alcaligenes/metabolismo , Aminohidrolasas/química , Aminohidrolasas/genética , Cationes Bivalentes/química , Clonación de Organismos/métodos , Ácido Edético/química , Escherichia coli/genética , Escherichia coli/aislamiento & purificación , Escherichia coli/metabolismo , Concentración de Iones de Hidrógeno , Hidrólisis , Cinética , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/aislamiento & purificación , Estereoisomerismo , Especificidad por Sustrato/genética , TemperaturaRESUMEN
(R)-(-)-Mandelic acid (R-MA) is an important intermediate with broad uses. Recently, R-MA production using nitrilase has been gaining more and more attention due to its higher productivity and enantioselectivity. In this work, a new bacterium WT10, which exhibited favorable nitrilase activity and excellent enantioselectivity for production of R-MA by enantioselective biocatalytic hydrolysis of (R,S)-mandelonitrile, was isolated and identified as a strain of Alcaligenes faecalis. In order to improve its nitrilase activity for industrial application, the wild-type strain WT10 was further subjected to mutagenesis using a combined LiCl-ultraviolet irradiation and low energy N(+) ion beams implantation technique. A valuable mutant strain A. faecalis ZJUTB10 was obtained. The nitrilase specific activity of the mutant strain was greatly improved up to 350.8 U g(-1), in comparison with wild-type strain WT10 of 53.09 U g(-1). The reaction conditions for R-MA production by mutant strain A. faecalis ZJUTB10 were also optimized. Nitrilase activity in mutant strain showed a broad pH optimum at pH 7.7-8.5. The optimal temperature was 35°C. The highest production rate reached 9.3 mmol h(-1) g(-1). The results showed that mutant strain A. faecalis ZJUTB10 was a new candidate for efficient R-MA production from (R,S)-mandelonitrile and could potentially be used in industrial production.
Asunto(s)
Acetonitrilos/metabolismo , Biocatálisis , Biotecnología , Ácidos Mandélicos/síntesis química , Alcaligenes faecalis/clasificación , Alcaligenes faecalis/enzimología , Alcaligenes faecalis/genética , Alcaligenes faecalis/aislamiento & purificación , Aminohidrolasas/metabolismo , Biotecnología/métodos , Concentración de Iones de Hidrógeno , Hidrólisis , Datos de Secuencia Molecular , Mutación , Filogenia , ARN Ribosómico 16S/genética , Microbiología del Suelo , TemperaturaRESUMEN
The enantioselective reduction of methyl benzoylformate to (R)-methyl mandelate, an important pharmaceutical intermediate and a versatile resolving agent, was investigated in this study. After minimizing the reaction-specific constraints (constraints dependent on the nature of the substrate and product) by preliminary selection of the reaction parameters, an effective whole cell biocatalyst (Saccharomyces cerevisiae AS2.1392) was obtained by simple screening procedures. Under further optimized conditions, a product concentration of 103 mmol L(-1) could be attained within 5 h with a yield of 85.8% and an enantiometric excess of 95.4%, indicating S. cerevisiae AS2.1392 an efficient biocatalyst for the asymmetric synthesis of (R)-methyl mandelate. Furthermore, resin-based in situ product removal (ISPR) technique was applied to alleviate the substrate and product inhibition or toxicity to the whole cells. The integration of newly isolated biocatalyst and proper ISPR technique provides a practical route for the preparation of optically active pharmaceutical intermediates.
Asunto(s)
Glioxilatos/metabolismo , Ácidos Mandélicos/aislamiento & purificación , Ácidos Mandélicos/metabolismo , Resinas Sintéticas/química , Saccharomyces cerevisiae/metabolismo , Absorción , Catálisis , Glioxilatos/química , Ácidos Mandélicos/síntesis química , Integración de SistemasRESUMEN
Mandelic acid was synthesized from benzaldehyde with chloroform in a 81% yield at 60 degrees C for 2 h by using triethylbenzylammonium chloride (TEBA) and poly(ethylene glycol)-800 (PEG-800) as a complex phase transfer catalyst under ultrasonic irradiation. The main advantages of this present method are that the reaction time is much shorter and the yield is higher than those of the classical method. p-Methoxymandelic acid was also obtained in a 84% yield under the same reaction conditions.
Asunto(s)
Ácidos Mandélicos/síntesis química , Catálisis , Cloroformo/química , Indicadores y Reactivos , Ácidos Mandélicos/efectos de la radiación , Polietilenglicoles/química , Solventes/química , UltrasonidoRESUMEN
The proof of concept experiments of fluorous "racemic" mixture synthesis (FRMS) is shown using polysaccharide-based chiral stationary phases. The mixture of racemic O-benzoylmandelate derivatives bearing different lengths of fluorous cleavable tags undergoes sequential reactions to provide individual derivatives as well as their enantiomers resolved on polysaccharide-based chiral HPLC columns (DAICEL CHIRALCEL and CHIRALPAK series).