- Synthesis of hydroxytyrosol, 2-hydroxyphenylacetic acid, and 3-hydroxyphenylacetic acid by differential conversion of tyrosol isomers using Serratia marcescens strain
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We investigated to develop an effective procedure to produce the potentially high-added-value phenolic compounds through bioconversion of tyrosol isomers. A soil bacterium, designated Serratia marcescens strain, was isolated on the basis of its ability to grow on p-tyrosol (4-hydroxyphenylethanol) as a sole source of carbon and energy. During growth on p-tyrosol, Ser. marcescens strain was capable of promoting the formation of hydroxytyrosol. To achieve maximal hydroxytyrosol yield, the growth state of the culture utilized for p-tyrosol conversion as well as the amount of p-tyrosol that was treated were optimized. The optimal yield of hydroxytyrosol (80%) was obtained by Ser. marcescens growing cells after a 7-h incubation using 2 g/L of p-tyrosol added at the end of the exponential phase to a culture pregrown on 1 g/L of p-tyrosol. Furthermore, the substrate specificity of the developed biosynthesis was investigated using m-tyrosol (3-hydroxyphenylethanol) and o-tyrosol (2-hydroxyphenylethanol) as substrates. Ser. marcescens strain transformed completely m-tyrosol and o-tyrosol into 3-hydroxyphenylacetic acid and 2-hydroxyphenylacetic acid, respectively, via the oxidation of the side chain carbon of the treated substrates. This proposed procedure is an alternative approach to obtain hydroxytyrosol, 2-hydroxyphenylacetic acid, and 3-hydroxyphenylacetic acid in an environmentally friendly way which could encourage their use as alternatives in the search for replacement of synthetic food additives.
- Allouche, Noureddine,Sayadi, Sami
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- Antioxidant activity of olive phenols: Mechanistic investigation and characterization of oxidation products by mass spectrometry
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In this work, the antioxidant activity of olive phenols is first characterized by their stoichiometries ntot (number of radicals trapped per antioxidant molecule) and their rate constants for the first H-atom abstraction k1, by the stable radical DPPH. It appears that oleuropein, hydroxytyrosol and caffeic acid have the largest k1 values, whereas dihydrocaffeic acid, an intestinal metabolite of caffeic acid, is the best antioxidant in terms of ntot. For phenols with a catechol moiety ntot1 is higher than two, implying an antioxidant effect of their primarily formed oxidation products. A HPLC-MS analysis of the main products formed in the AAPH-induced oxidation of olive phenols reveals the presence of dimers and trimers. With hydroxytyrosol and dihydrocaffeic acid, oligomerization can take place with the addition of water molecules. The antioxidant activity of olive phenols is then evaluated by their ability to inhibit the AAPH-induced peroxidation of linoleic acid in SDS micelles. It is shown that olive phenols and quercetin act as retardants rather than chain breakers like α-tocopherol. From a detailed mechanistic investigation, it appears that the inhibition of lipid peroxidation by olive phenols can be satisfactorily interpreted by assuming that they essentially reduce the AAPH-derived initiating radicals. Overall, olive phenols prove to be efficient scavengers of hydrophilic peroxyl radicals with a long lasting antioxidant effect owing to the residual activity of some of their oxidation products.
- Roche, Marjolaine,Dufour, Claire,Mora, Nathalie,Dangles, Olivier
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- Hydroxytyrosol lipophilic analogues: Enzymatic synthesis, radical scavenging activity and DNA oxidative damage protection
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The olive oil phenol hydroxytyrosol (3), as well its metabolite homovanillic alcohol (4), were subjected to chemoselective lipase-catalysed acylations, affording with good yield 10 derivatives (5-14) bearing C2, C3, C4, C10 and C18 acyl chains at C-1. Hydroxytyrosol (3) and its lipophilic derivatives showed very good DPPH{radical dot} radical scavenging activity. Compounds 3, 4 and their lipophilic analogues 5-14 were subjected to the atypical Comet test on whole blood cells: 3 and its analogues 5 and 6, with little hydrophobic character (log P ≤ 1.20), showed a good protective effect against H2O2 induced oxidative DNA damage. The homovanillic alcohol 4 and its analogues 10-14 resulted scarcely effective both as radical scavengers and antioxidant agents.
- Grasso, Salvatore,Siracusa, Laura,Spatafora, Carmela,Renis, Marcella,Tringali, Corrado
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- Synthesis of tritium-labeled hydroxytyrosol, a phenolic compound found in olive oil
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(3,4-Dihydroxyphenyl)ethanol, commonly known as hydroxytyrosol (1), is the major phenolic antioxidant compound in olive oil, and it contributes to the beneficial properties of olive oil. Bioavailability and metabolism studies of this compound are extremely limited, in part, related to unavailability of radiolabeled compound. Studies with radiolabeled compounds enable use of sensitive radiometric analytical methods as well as aiding elucidation of metabolic and elimination pathways. In the present study a route for the formation of hydroxytyrosol (1), by reduction of the corresponding acid 2 with tetrabutylammonium boronate, was found. Methods for the incorporation of a tritium label in 1 were investigated and successfully accomplished. Tritiated hydroxytyrosol (1t) was synthesized with a specific activity of 66 Ci/mol. The stability of unlabeled and labeled hydroxytyrosol was also investigated.
- Tuck, Kellie L.,Tan, Hai-Wei,Hayball, Peter J.
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- Determination of phenols, flavones, and lignans in virgin olive oils by solid-phase extraction and high-performance liquid chromatography with diode array ultraviolet detection
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A simple analytical method for the quantitative determination of phenols, flavones, and lignans in virgin olive oils was developed. The polar fraction was isolated from small amounts of oil sample (2.5 g) by solid-phase extraction (SPE) using diol-phase cartridges, and the extract was analyzed by reversed-phase HPLC coupled with diode array LTV detection. Chromatographic separation of pinoresinol, cinnamic acid, and 1-acetoxypinoresinol was achieved. Repeatability (RSD 90%), and response factors for each identified component were determined. SPE on amino-phase cartridges was used for isolating acidic phenols and as an aid for phenol identification. For the first time, 2-(4-hydroxyphenyl)ethyl acetate was detected in olive oils. The aldehydic structure of the ligstroside aglycon was confirmed by NMR spectroscopy. The colorimetric determination of total o-diphenolic compounds by reaction with molybdate was consistent with their HPLC determination. Differences between results obtained by liquid-liquid extraction and SPE were not statistically significant.
- Mateos, Raquel,Espartero, Jose Luis,Trujillo, Mariana,Rios,Leon-Camacho, Manuel,Alcudia, Felipe,Cert, Arturo
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- A highly convenient synthesis of hydroxytyrosol and its recovery from agricultural waste waters
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Hydroxytyrosol, a polyphenol with very interesting antioxidant properties, which naturally occurs in virgin olive oil and mainly in olive oil mill waste waters, was synthesized by reducing 3,4-dihydroxyphenylacetic acid with LiAlH4 in tetrahydrofuran under refluxing for 2 h. The yield of reaction was 82.8%. The spectroscopic and HPLC data of the synthesized compound proved to coincide fully with those of a pure sample obtained by the chromatographic recovery from olive oil mill waste waters (yield = 91 mg/L). This synthetic method appears to be the most convenient compared with those reported in the literature and is more convenient than the chromatographic recovery. The tri- and diacetyl derivatives of the synthetic compound were also prepared for structure-bioactivity relationship studies. A brief discussion is given on the economical and ecological aspects regarding the production of hydroxytyrosol.
- Capasso, Renato,Evidente, Antonio,Avolio, Salvatore,Solla, Francesco
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- Oxidative cleavage of 1-aryl-isochroman derivatives using the: Trametes villosa laccase/1-hydroxybenzotriazole system
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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.
- Bernini, Roberta,Crisante, Fernanda,D'Acunzo, Francesca,Gentili, Patrizia,Ussia, Emanuele
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- Determination of hydroxytyrosol in plasma by HPLC
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Hydroxytyrosol (2-(3,4-dihydroxyphenyl)ethanol), a phenolic compound present in extravirgin olive oil, has been reported to contribute to the prevention of cardiovascular disease. The present study describes an accurate and reproducible reversed-phase HPLC method to measure hydroxytyrosol in plasma. This compound was extracted from acidified plasma by solid-phase extraction using an Oasis HLB copolymer. The plasma sample was rinsed with water and methanol in water (5:95; v/v). Hydroxytyrosol was eluted with methanol, which was subsequently evaporated under a nitrogen stream. Analysis by HPLC with diode array-UV detection was carried out using a C18 column and a gradient elution with acidified water and methanol/acetonitrile (50:50; v/v). The method was validated by the analyses of plasma samples spiked with pure hydroxytyrosol, obtaining a linear correlation (0.9986) and precision with a coefficient of variation ranging from 0.79 to 6.66%. The recovery was ?100%, and the limit of detection was 37 ng/mL. The oral administration of hydroxytyrosol to rats and its subsequent detection in plasma showed that the method is suitable for pharmacokinetic studies.
- Ruiz-Gutierrez,Juan,Cert,Planas
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- Characterization of Type IV Carboxylate Reductases (CARs) for Whole Cell-Mediated Preparation of 3-Hydroxytyrosol
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Fragrance and flavor industries could not imagine business without aldehydes. Processes for their commercial production raise environmental and ecological concerns. The chemical reduction of organic acids to aldehydes is challenging. To fulfill the demand of a mild and selective reduction of carboxylic acids to aldehydes, carboxylic acid reductases (CARs) are gaining importance. We identified two new subtype IV fungal CARs from Dichomitus squalens CAR (DsCAR) and Trametes versicolor CAR (Tv2CAR) in addition to literature known Trametes versicolor CAR (TvCAR). Expression levels were improved by the co-expression of GroEL-GroES with either the trigger factor or the DnaJ-DnaK-GrpE system. Investigation of the substrate scope of the three enzymes revealed overlapping substrate-specificities. Tv2CAR and DsCAR showed a preferred pH range of 7.0 to 8.0 in bicine buffer. TvCAR showed highest activity at pH 6.5 to 7.5 in MES buffer and slightly reduced activity at pH 6.0 or 8.0. TvCAR appeared to tolerate a wider pH range without significant loss of activity. Type IV fungal CARs optimal temperature was in the range of 25–35 °C. TvCAR showed a melting temperature (Tm) of 55 °C indicating higher stability compared to type III and the other type IV fungal CARs (Tm 51–52 °C). Finally, TvCAR was used as the key enzyme for the bioreduction of 3,4-dihydroxyphenylacetic acid to the antioxidant 3-hydroxytyrosol (3-HT) and gave 58 mM of 3-HT after 24 h, which correlates to a productivity of 0.37 g L?1 h?1.
- Horvat, Melissa,Fritsche, Susanne,Kourist, Robert,Winkler, Margit
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- High-yielding preparation of a stable precursor of hydroxytyrosol by total synthesis and from the natural glycoside oleuropein
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The unprecedented acetonide of the antioxidant hydroxytyrosol has been synthesized by a two-step high-yielding procedure and found to be both purifiable by chromatography and stable over a wide pH range. The protection stabilizes hydroxytyrosol against oxidation, thereby allowing long-term storage. The protection can quantitatively be removed, under nonaqueous conditions, to afford pure hydroxytyrosol suitable for use as an additive in food and cosmetic preparations. Extension of the same methodology to the natural and easily accessible glycoside oleuropein, followed by saponification of the resulting complex mixture of acetonides, allowed hydroxytyrosol acetonide to be recovered in high yield. This constitutes a new interesting methodology to obtain the antioxidant hydroxytyrosol.
- Gambacorta, Augusto,Tofani, Daniela,Bernini, Roberta,Migliorini, Antonella
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- Effect of lipophilization of hydroxytyrosol on its antioxidant activity in fish oils and fish oil-in-water emulsions
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The effect of lipophilization of the antioxidant efficiency of hydroxytyrosol on fish oil enriched systems was studied. Hydroxytyrosol fatty acid esters with increasing size of the alkyl chain and different lipophlllclty were tested in bulk fish oils and fish oil-ln-water emulsions. Results showed a significant antioxidant activity of hydroxytyrosol esters in both systems especially in emulsions. The introduction of a lipophilic chain decreased the antioxidant effectiveness of hydroxytyrosol in homogeneous systems as fish oils. In emulsion systems, the presence of a short - medium lipophilic chain (acetate, butyrate or octanoate) improved the antioxidant efficiency of hydroxytyrosol favoring the physical location of the antioxidant in the interface, but longer alkyl chain (laurate) maintained or even decreased their antioxidant activity. A maximum of antioxidant efficiency seems to appear when the chain length of the hydroxytyrosol derivative is that of eight carbons which Is probably associated with a preferential location of the diorthophenolic moiety in the right geometry. These results are of high importance for the optimum design of effective antioxidants for omega 3 enriched foods, which are very susceptible to suffer oxidation and, then, rancidity.
- Medina,Lois,Alcantara,Lucas,Morales
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- HYDROXYCINNAMIC ACID ESTERS OF PHENETHYLALCOHOL GLYCOSIDES FROM REHMANNIA GLUTINOSA VAR. PURPUREA
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Five new hydroxycinnamic acid esters of phenethylalcohol glycosides named jionosides C, D, E, A2 and B2, together with nine known compounds, have been isolated from roots of Rehmannia glutinosa var. purpurea and their structures elucidated on the basis of chemical and spectral evidences. Key Word Index-Rehmannia glutinosa var. purpurea; Scrophulariaceae; phenethylalcohol glycosides; jionosides.
- Sasaki, Hiroshi,Nishimura, Hiroaki,Chin (Chen Zhengxiong), Masao,Mitsuhashi, Hiroshi
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- Main antimicrobial compounds in table olives
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The inhibitors involved in the lactic acid fermentation of table olives were investigated in aseptic olive brines of the Manzanilla and Gordal varieties. Phenolic and oleosidic compounds in these brines were identified by high-performance liquid chromatography with ultraviolet and electrospray ionization mass spectrometry detection, and several substances were also characterized by nuclear magnetic resonance. Among these compounds, the dialdehydic form of decarboxymethyl elenolic acid linked to hydroxytyrosol showed the strongest antilactic acid bacteria activity, and its presence in brines could explain the growth inhibition of these microorganisms during olive fermentation. However, it was found that the dialdehydic form of decarboxymethyl elenolic acid, identified for the first time in table olives, and an isomer of oleoside 11-methyl ester were also effective against Lactobacillus pentosus and can, therefore, contribute to the antimicrobial activity of olive brines. It must also be stressed that the three new inhibitors discovered in table olive brines exerted a more potent antibacterial activity than the well-studied oleuropein and hydroxytyrosol.
- Medina, Eduardo,Brenes, Manuel,Romero, Concepcion,Garcia, Aranzazu,De Castro, Antonio
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- Determination of Synthetic Hydroxytyrosol in Rat Plasma by GC-MS
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2-(3,4-Dihydroxyphenyl)ethanol (DPE), the major phenolic compound in olive oil, may contribute the antioxidative activities and other beneficial effects to olive oil. However, the lack of commercial available DPE and procedures sensitive enough to quantitatively determine DPE in body fluids have limited the bioavailability and metabolism studies on this phenolic compound. In the present study, DPE was synthesized with high yield and high purity and administered orally to rats. DPE concentration in rat plasma, after absorption, was measured using a sensitive GC-MS-SIM method. The results indicated that the highest level of DPE in plasma was detected at 5-10 min after administration. During this period, the concentration of DPE fluctuated widely with the individual.
- Bai, Chen,Yan, Xiaojun,Takenaka, Makiko,Sekiya, Keizo,Nagata, Tadahiro
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- Synthesis of the antioxidant hydroxytyrosol using tyrosinase as biocatalyst
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Hydroxytyrosol (HTyr), a natural ortho-diphenolic antioxidant with health-beneficial properties that mainly occurs in virgin olive oil and olive oil mill waste waters (also known as vegetative waters), has been enzymatically synthesized using mushroom tyrosinase. This o-diphenol (not commercially available) was obtained from its monophenolic precursor tyrosol (commercially available) in the presence of both tyrosinase and ascorbic acid. The reaction synthesis is continuous, easy to perform, and adaptable to a bioreactor for industrial purposes. The HTyr concentration is time-predicted, and the yield of reaction can be 100%. The synthesis method reported here is an alternative approach to obtain this compound in an environmentally friendly way.
- Espin, Juan Carlos,Soler-Rivas, Cristina,Cantos, Emma,Tomas-Barberan, Francisco A.,Wichers, Harry J.
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- Production of hydroxytyrosol from hydroxylation of tyrosol by Rhodococcus pyridinivorans 3HYL DSM109178
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Hydroxytyrosol (4-(2-hydroxyethyl)-1,2-benzenediol) is the most known bioactive compound from the plant Olea europaea (olive tree). To date, few biocatalysis processes allowing efficient production of hydroxytyrosol from potential substrates including, tyrosol (2-(4-hydroxy) phenyl ethanol) and tyrosine have been reported. In this paper, we report for a Gram-positive bacterium that produces hydroxytyrosol via conversion of tyrosol and/or L-tyrosine, identified as a Rhodococcus pyridinivorans based on phenotypic characteristics and 16S rDNA sequence, and designated R. pyridinivorans strain 3HYL DSM109178. Interestingly, strain 3HYL shows an outstanding production of hydroxytyrosol from tyrosol up to 16.4 ± 0.23 mmol/L with high kinetic parameters exceeding the reported values. However, a slight downstream metabolism of the product is assigned to the wild-type strain during the stationary phase of growth. The plasmid-cured strain was obtained using random chemical mutagenesis, designated R. pyridinivorans 3HYL-AO, and was able to produce hydroxytyrosol, with yields up to 21.75 ± 0.34 mmol/L. Moreover, the plasmid-cured strain exhibited a significant reduction in the transformation to its acetic acid forms compared to the wild-type strain as depicted by HPLC analysis. Comparison of kinetic data of the bioconversion/accumulation process between the wild type and mutant strain, in the presence and absence of L-tyrosine, and thus suggesting the occurrence of an upstream pathway for synthesis of tyrosol via (L)-tyrosine.
- Anissi, Jaouad,Sendide, Khalid,Ouardaoui, Abdelkrim,Benlemlih, Mohammed,El Hassouni, Mohammed
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- Whole-cell carboxylate reduction for the synthesis of 3-hydroxytyrosol
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3-Hydroxytyrosol (3-HT) is a phenolic antioxidant that has a number of beneficial effects on human health and is a valuable building block in the synthesis of various pharmaceuticals. Herein, we report a new method for the production of 3-HT through reduction of 3,4-dihydroxyphenylacetic acid. The reduction was performed in whole Escherichia coli BL21 (DE3) cells overexpressing carboxylic acid reductase from Nocardia and phosphopantetheinyl transferase from E. coli. An endogenous E. coli aldehyde reducing activity turned out to be highly efficient for further reduction of the aldehyde intermediate to the desired alcohol. The influence of different buffer components, cofactors, and cofactor recycling systems was investigated. A very economic combination of glucose, citrate, and air proved sufficient for recycling of the essential cofactors ATP and NAD(P)H. Selected crucial parameters were then further optimized within a "design of experiments" approach. Finally, first preparative-scale bioreductions resulted in pure 3-HT. All in a cell's work: An enzymatic carboxylic acid reduction is the key step of a new route to the potent antioxidant from olives: 3-hydroxytyrosol. In addition to the substrate 3,4-dihydroxyphenylacetic acid, only citrate, glucose, and oxygen are required to regenerate the essential cofactors ATP and NAD(P)H. CAR=carboxylate reductase; PPTase= phosphopantetheinyl transferase.
- Napora-Wijata, Kamila,Robins, Karen,Osorio-Lozada, Antonio,Winkler, Margit
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- Synthesis and Antioxidant Activity of Hydroxytyrosol Alkyl-Carbonate Derivatives
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Three procedures have been investigated for the isolation of tyrosol (1) and hydroxytyrosol (2) from a phenolic extract obtained from the solid residue of olive milling. These three methods, which facilitated the recovery of these phenols, were chemical or enzymatic acetylation, benzylation, and carbomethoxylation, and subsequent carbonylation or acetonation reactions. Several new lipophilic alkyl-carbonate derivatives of hydroxytyrosol have been synthesized, coupling the primary hydroxy group of this phenol, through a carbonate linker, using alcohols with different chain lengths. The antioxidant properties of these lipophilic derivatives have been evaluated by different methods and compared with free hydroxytyrosol (2) and also with the well-known antioxidants BHT and α-tocopherol. Three methods were used for the determination of this antioxidant activity: FRAP and ABTS assays, to test the antioxidant power in hydrophilic media, and the Rancimat test, to evaluate the antioxidant capacity in a lipophilic matrix. These new alkyl-carbonate derivatives of hydroxytyrosol enhanced the antioxidant activity of this natural phenol, with their antioxidant properties also being higher than those of the commercial antioxidants BHT and α-tocopherol. There was no clear influence of the side-chain length on the antioxidant properties of the alkyl-carbonate derivatives of 2, although the best results were achieved mainly by the compounds with a longer chain on the primary hydroxy group of this natural phenolic substance.
- Fernandez-Pastor, Ignacio,Fernandez-Hernandez, Antonia,Rivas, Francisco,Martinez, Antonio,Garcia-Granados, Andres,Parra, Andres
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- Acteoside as the analgesic principle of Cedron (Lippia triphylla), a Peruvian medicinal plant
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Acteoside (verbascoside) was isolated as an analgesic principle from Cedron (leaves and stem of Lippia triphylla (L'HER) O. KUNTZE; Verbenaceae), a Peruvian medicinal plant, by activity-guided separation. The compound exhibited analgesia on acetic acid-induced writhing and on tail pressure pain in mice by the oral administration of 300mg/kg and 100mg/kg, respectively. Acteoside also caused weak sedation by its effect on the prolongation of pentobarbital-induced anesthesia and on the depression of locomotion enhanced by methamphetamine. An intravenous injection of acteoside reduced the effective dose to 2mg/kg by the writhing method. Thirteen related compounds were tested for the activity by intravenous and oral administration to obtain information on the active structure.
- Nakamura, Tomonori,Okuyama, Emi,Tsukada, Atsushi,Yamazaki, Mikio,Satake, Motoyoshi,Nishibe, Sansei,Deyama, Takeshi,Moriya, Akira,Maruno, Masao,Nishimura, Hiroaki
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- Potential antitumor agents from Lantana camara: Structures of flavonoid-, and phenylpropanoid glycosides
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Besides the known glycosides, verbascoside and a flavone glycoside, a novel flavonol glycoside named camaraside and a new phenylpropanoid glycoside, lantanaside have been isolated from the leaves of Lantana camara and defined as 3,5-dihydroxy-4',6-dimethoxyflavonol-7-O-glucopyranoside and 3,4-dihydroxy-β-phenylethyl-O-α-L-rhamnopyranosyl (1 → 3)-4-O-cis-caffeoyl-β-D-glucopyranoside respectively by spectroscopic methods and chemical transformations.
- Mahato,Sahu,Roy,Sharma
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- Oxidative chemistry of the natural antioxidant hydroxytyrosol: Hydrogen peroxide-dependent hydroxylation and hydroxyquinone/o-quinone coupling pathways
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Oxidation of the natural antioxidant hydroxytyrosol (1) with peroxidase/H2O2 in phosphate buffer at pH 7.4 led to the formation of two main ethyl acetate-extractable products. These could be isolated by preparative TLC after reduction and acetylation, and were identified as the tetraacetyl derivative of 2-(2,4,5-trihydroxyphenyl)ethanol (3) and the heptaacetyl derivative of the pentahydroxybiphenyl 4 by 2D NMR and MS analysis. Similar oxidation of 4-methylcatechol gave, after the same work-up, the acetylated derivatives of 1,2,4-trihydroxy-5-methylbenzene (5) and the pentahydroxybiphenyl 6. Mechanistic experiments suggested that hydrogen peroxide affects the course of the oxidation of 1 by adding to the first formed o-quinone to give a hydroxyquinone intermediate. This could bring nucleophilic attack to the o-quinone of 1 to give the dimer 4. These results disclose novel oxidative pathways of 4-alkylcatechols and provide an improved chemical basis to enquire into the mechanism of the antioxidant action of 1.
- De Lucia, Maria,Panzella, Lucia,Pezzella, Alessandro,Napolitano, Alessandra,D'Ischia, Marco
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- Two new phenylethanoid glycosides from Ginkgo biloba leaves and their tyrosinase inhibitory activities
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Two undescribed phenylethanoid glycosides, Ginkgoside C (1) and D (2), together with ten known glycosides (3?12) were isolated from Ginkgo biloba leaves. Their structures were characterized by physical data analyses such as NMR, HRESIMS, as well as chemical hydrolysis. All compounds were tested for their tyrosinase inhibitory activities. At a concentration of 25 μM, compounds 2, 4, 5, 6, and 11 showed obvious mushroom tyrosinase inhibition activities, with percentinhibition values of 19.12 ± 2.59percent, 25.79 ± 1.83percent, 16.07 ± 1.07percent, 24.46 ± 1.10percent, 18.64 ± 3.62percent, respectively, with kojic acid used as the positive control (27.50 ± 2.72percent).
- Fei, Yingying,Li, Junping,Liu, Anqi,Liu, Wanrong,Niu, Haoying,Shu, Penghua,Wei, Xialan,Xiao, Fugang,Xu, Zhihong,Zhang, Lingxiang
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- Novel approach to the detection and quantification of phenolic compounds in olive oil based on 31P nuclear magnetic resonance spectroscopy
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31P NMR spectroscopy has been employed to detect and quantify phenolic compounds in the polar fraction of virgin olive oil. This novel analytical method is based on the derivatization of the hydroxyl and carboxyl groups of phenolic compounds with 2-chloro-4,4,5,5-tetramethyldioxaphospholane and the identification of the phosphitylated compounds on the basis of the 31P chemical shifts. Quantification of a large number of phenolic compounds in virgin olive oil can be accomplished by integration of the appropriate signals in the 31P NMR spectrum and the use of the phosphitylated cyclohexanol as internal standard. Finally, the validity of this technique for quantitative measurements was thoroughly examined.
- Christophoridou, Stella,Dais, Photis
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- Thiols Act as Methyl Traps in the Biocatalytic Demethylation of Guaiacol Derivatives
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Demethylating methyl phenyl ethers is challenging, especially when the products are catechol derivatives prone to follow-up reactions. For biocatalytic demethylation, monooxygenases have previously been described requiring molecular oxygen which may cause oxidative side reactions. Here we show that such compounds can be demethylated anaerobically by using cobalamin-dependent methyltransferases exploiting thiols like ethyl 3-mercaptopropionate as a methyl trap. Using just two equivalents of this reagent, a broad spectrum of substituted guaiacol derivatives were demethylated, with conversions mostly above 90 %. This strategy was used to prepare the highly valuable antioxidant hydroxytyrosol on a one-gram scale in 97 % isolated yield.
- Grimm, Christopher,Kroutil, Wolfgang,Pompei, Simona,Schiller, Christine,Schober, Lukas
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- A two-step process for the synthesis of hydroxytyrosol
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A new process for the synthesis of hydroxytyrosol (3,4-dihy-droxyphenylethanol), the most powerful natural antioxidant currently known, by means of a two-step approach is reported. Catechol is first reacted with 2,2-dimethoxyacetaldehyde in basic aqueous medium to produce the corresponding mandelic derivative with > 90 % conversion of the limiting reactant and about 70 % selectivity to the desired para-hydroxyalkylat-ed compound. Thereafter, the intermediate is hydrogenated to hydroxytyrosol by using a Pd/C catalyst, with total conversion of the mandelic derivative and 68 % selectivity. This two-step process is the first example of a synthetic pathway for hydroxytyrosol that does not involve the use of halogenated components or reduction methodologies that produce stoichiometric waste. It also avoids the complex procedure currently used for hydroxytyrosol purification when it is extracted from wastewa-ter of olive oil production.
- Ziosi, Paolo,Paolucci, Claudio,Santarelli, Francesco,Tabanelli, Tommaso,Passeri, Sauro,Cavani, Fabrizio,Righi, Paolo
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- Expedient synthesis of hydroxytyrosol and its esters
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An efficient and friendly method for obtaining hydroxytyrosol from tyrosol, a component of olive waste, is reported. Hydroxytyrosol also may be obtained in the form of enzymatically convertible precursors (e.g., hydroxytyrosyl acetate), thus increasing the stability of the active principle. Copyright Taylor & Francis Group, LLC.
- Bovicelli, Paolo,Antonioletti, Roberto,Mancini, Silvia,Causio, Stefano,Borioni, Giorgio,Ammendola, Sergio,Barontini, Maurizio
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- Regioselectivity of Cobalamin-Dependent Methyltransferase Can Be Tuned by Reaction Conditions and Substrate
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Regioselective reactions represent a significant challenge for organic chemistry. Here the regioselective methylation of a single hydroxy group of 4-substituted catechols was investigated employing the cobalamin-dependent methyltransferase from Desulfitobacterium hafniense. Catechols substituted in position four were methylated either in meta- or para-position to the substituent depending whether the substituent was polar or apolar. While the biocatalytic cobalamin dependent methylation was meta-selective with 4-substituted catechols bearing hydrophilic groups, it was para-selective for hydrophobic substituents. Furthermore, the presence of water miscible co-solvents had a clear improving influence, whereby THF turned out to enable the formation of a single regioisomer in selected cases. Finally, it was found that also the pH led to an enhancement of regioselectivity for the cases investigated.
- Pompei, Simona,Grimm, Christopher,Farnberger, Judith E.,Schober, Lukas,Kroutil, Wolfgang
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- Improving process conditions of hydroxytyrosol synthesis by toluene-4-monooxygenase
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Toluene-4-monooxygenase from Pseudomonas mendocina KR1 was recently engineered for the synthesis of hydroxytyrosol, a potent antioxidant. Following a 190-fold improvement in the enzyme activity by protein engineering means, improving the process conditions of this biocatalytic route was under taken for developing a liter-scale bioprocess. The growth stage was improved by selection of a rich media and harvesting the cells at the end of the logarithmic stage. The biotransformation stage was optimized by evaluating substrate concentration, cell density, and different operational modes. It was found that although reusing the cells in successive batch modes is feasible, their activity is dramatically decreased after the first use. In comparison, the activity of the cells following subsequent substrate addition in a fed batch mode was only slightly decreased. Furthermore, a better yield was obtained by extending the duration of the biotransformation stage, rather than adding more substrate. An overall concentration of 133 mg/L HTyr, corresponding to a volumetric productivity of 54 mg/L/h and a yield of 48% was achieved by a batch mode using 2 mM substrate. This is an order of magnitude improvement compared with the enzyme productivity before the process optimization. The use of beads conjugated with phenylboronic acid residues for adsorbing the product from the biotransformation bulk was evaluated. Though the recovery yield and purity were shown to be oppositely dependent, an average recovery procedure led to 2-fold purification of HTyr resulting in 84% purity with 70% recovery yield.
- Brouk, Moran,Fishman, Ayelet
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- Isolation of natural compounds from Phlomis stewartii showing α-glucosidase inhibitory activity
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Stewartiiside (1), a phenylethanoid glycoside and three 28-nortriterpenoids: stewertiisins A-C [(17R)-19(18 → 17)-abeo-3α, 18β,23,24-tetrahydroxy-28-norolean-12-ene, 2; (17R)-19(18 → 17)-abeo-2α,16β,18β,23,24-pentahydroxy-28-norolean-12-en-3-one, 3; (17R)-19(18 → 17)-abeo-2α,3α,23,24-tetrahydroxy-28- noroleane-11,13-diene, 4] together with eight known compounds: lunariifolioside (5), notohamosin A (6), phlomispentanol (7), isorhamnetin 3-(6-p-coumaroyl)- β-d-glucopyranoside (8), tiliroside (9), caffeic acid (10), p-hydrxybenzoic acid (11) and oleanolic acid (12) were isolated from the ethyl acetate soluble fraction of the methanolic extract of whole plant of Phlomis stewartii. The structures of these isolates (1-12) were elucidated by the combination of 1D (1H and 13C NMR), 2D (HMQC, HMBC COSY, NOESY) NMR spectroscopy and mass spectrometry (EIMS, HREIMS, FABMS, HRFABMS) and in comparison with literature data of related compounds. All the isolates (1-12) showed α-glucosidase inhibitory activity with IC50 values ranging between 14.5 and 355.4 μM, whereas, compounds 1, 5, 9 and 10 showed promising α-glucosidase inhibitory activity with IC50 values below 30 μM.
- Jabeen, Bushra,Riaz, Naheed,Saleem, Muhammad,Naveed, Muhammad Akram,Ashraf, Muhammad,Alam, Umber,Rafiq, Hafiza Mehwish,Tareen, Rasool Bakhsh,Jabbar, Abdul
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Read Online
- Synthesis and biological evaluation of caffeic acid 3,4-dihydroxyphenethyl ester
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A high-yield synthesis of caffeic acid 3,4-dihydroxyphenethyl ester (1) has been achieved through Knoevenagel condensation of 3,4-dihydroxybenzaldehyde and 3,4-dihydroxyphenethyl monomalonate as the key step. Compound 1 was tested against a 56-cell-line cytotoxicity panel and for its free-radical-scavenging activity in the DPPH test.
- Zhang, Zhizhen,Xiao, Binghua,Chen, Qi,Lian, Xiao-Yuan
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Read Online
- Hydroxytyrosol, a phenolic compound from virgin olive oil, prevents macrophage activation
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We investigated the effect of hydroxytyrosol (HT), a phenolic compound from virgin olive oil, on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in J774 murine macrophages stimulated with lipopolysaccharide (LPS). Incubation of cells with LPS caused an increase in iNOS and COX-2 mRNA and protein level as well as ROS generation, which was prevented by HT. In addition, HT blocked the activation of nuclear factor-κB (NF-κB), signal transducer and activator of transcription-1α (STAT-1α) and interferon regulatory factor-1 (IRF-1). These results, showing that HT down-regulates iNOS and COX-2 gene expression by preventing NF-κB, STAT-1α and IRF-1 activation mediated through LPS-induced ROS generation, suggest that it may represent a non-toxic agent for the control of pro-inflammatory genes. Springer-Verlag 2005.
- Maiuri, Maria Chiara,De Stefano, Daniela,Di Meglio, Paola,Irace, Carlo,Savarese, Maria,Sacchi, Raffaele,Cinelli, Maria Pia,Carnuccio, Rosa
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- Biochemical evaluation of a parsley tyrosine decarboxylase results in a novel 4-hydroxyphenylacetaldehyde synthase enzyme
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Plant aromatic amino acid decarboxylases (AAADs) are effectively indistinguishable from plant aromatic acetaldehyde syntheses (AASs) through primary sequence comparison. Spectroscopic analyses of several characterized AASs and AAADs were performed to look for absorbance spectral identifiers. Although this limited survey proved inconclusive, the resulting work enabled the reevaluation of several characterized plant AAS and AAAD enzymes. Upon completion, a previously reported parsley AAAD protein was demonstrated to have AAS activity. Substrate specificity tests demonstrate that this novel AAS enzyme has a unique substrate specificity towards tyrosine (km 0.46. mM) and dopa (km 1.40. mM). Metabolite analysis established the abundance of tyrosine and absence of dopa in parsley extracts. Such analysis indicates that tyrosine is likely to be the sole physiological substrate. The resulting information suggests that this gene is responsible for the in vivo production of 4-hydroxyphenylacetaldehyde (4-HPAA). This is the first reported case of an AAS enzyme utilizing tyrosine as a primary substrate and the first report of a single enzyme capable of producing 4-HPAA from tyrosine.
- Torrens-Spence, Michael P.,Gillaspy, Glenda,Zhao, Bingyu,Harich, Kim,White, Robert H.,Li, Jianyong
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- Production of high hydroxytyrosol yields via tyrosol conversion by Pseudomonas aeruginosa immobilized resting cells
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An immobilized whole cell system was successfully performed to produce the most powerful antioxidant, hydroxytyrosol. Bioconversion of tyrosol into hydroxytyrosol was achieved via the immobilization of Pseudomonas aeruginosa resting cells in calcium alginate beads. Immobilization was advantageous as it allows immobilized cells to tolerate a greater tyrosol concentration than free cells. The bioconversion yield reached 86% in the presence of 5 g L-1 of tyrosol when cells immobilized in alginate beads were carried out in single batches. Evaluation of kinetic parameters showed the maintenance of the same catalytic efficiency expressed as Kcat/Km for both free and immobilized cells. The use of immobilized cells in repeated batches demonstrated a notable activity stabilization since the biocatalyst reusability was extended for at least four batches with a molar yield greater than 85%.
- Bouallagui, Zouhaier,Sayadi, Sami
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Read Online
- Synthesis process of hydroxytyrosol and intermediate thereof
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The invention discloses a synthesis process of hydroxytyrosol and an intermediate thereof, and belongs to the technical field of synthesis. The synthesis process of the hydroxytyrosol intermediate comprises the following step: carrying out oxidation reaction on 2-(3-formyl-4-hydroxyphenyl) acetate to obtain the hydroxytyrosol intermediate. The synthesis process of hydroxytyrosol comprises the following steps: a, carrying out catalytic esterification reaction on p-hydroxyphenylacetic acid to prepare p-hydroxyphenylacetate; b, carrying out formylation reaction on the p-hydroxyphenylacetate to prepare 2-(3-formyl-4-hydroxyphenyl) acetate; c, 2-(3-formyl-4-hydroxyphenyl) acetate is subjected to an oxidation reaction, and a hydroxytyrosol intermediate is prepared; and d, carrying out reduction reaction on the hydroxytyrosol intermediate to obtain hydroxytyrosol. The preparation method disclosed by the invention is low in starting material price, mild in reaction condition in each step, high in yield and suitable for industrial production, and can effectively solve the problems that an existing method for preparing hydroxytyrosol is relatively high in cost and is not suitable for industrial large-scale production.
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- Rapid biosynthesis of phenolic glycosides and their derivatives from biomass-derived hydroxycinnamates
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Biomass-derived hydroxycinnamates (mainly includingp-coumaric acid and ferulic acid), which are natural sources of aromatic compounds, are highly underutilized resources. There is a need to upgrade them to make them economically feasible. Value-added phenolic glycosides and their derivatives, both belonging to a class of plant aromatic natural products, are widely used in the nutraceutical, pharmaceutical, and cosmetic industries. However, their complex aromatic structures make their efficient biosynthesis a challenging process. To overcome this issue, we created three novel synthetic cascades for the biosynthesis of phenolic glycosides (gastrodin, arbutin, and salidroside) and their derivatives (hydroquinone, tyrosol, hydroxytyrosol, and homovanillyl alcohol) fromp-coumaric acid and ferulic acid. Moreover, because the biomass-derived hydroxycinnamates directly provided aromatic units, the cascades enabled efficient biosynthesis. We achieved substantially high production rates (up to or above 100-fold enhancement) relative to the glucose-based biosynthesis. Given the ubiquity of the aromatic structure in natural products, the use of biomass-derived aromatics should facilitate the rapid biosynthesis of numerous aromatic natural products.
- Zhao, Mingtao,Hong, Xulin,Abdullah,Yao, Ruilian,Xiao, Yi
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supporting information
p. 838 - 847
(2021/02/09)
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- Transaminase-Mediated Amine Borrowing via Shuttle Biocatalysis
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Shuttle catalysis has emerged as a useful methodology for the reversible transfer of small functional groups, such as CO and HCN, and goes far beyond transfer hydrogenation chemistry. While a biocatalytic hydrogen-borrowing methodology is well established, the biocatalytic borrowing of alternative functional groups has not yet been realized. Herein, we present a new concept of amine borrowing via biocatalytic shuttle catalysis, which has no counterpart in chemo-shuttle catalysis and allows efficient intermolecular amine shuttling to generate reactive intermediates in situ. By coupling this dynamic exchange with an irreversible downstream step to displace the reaction equilibrium in the forward direction, high conversion to target products can be achieved. We showcase the potential of this amine-borrowing methodology using a biocatalytic equivalent of both the Knorr-pyrrole synthesis and Pictet-Spengler reaction.
- O'Reilly, Elaine,O'Sullivan, Rachel,Ryan, James,Taday, Freya
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supporting information
(2022/01/04)
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- A new secoiridoid glucoside from Olea europaea
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A new phenolic glucoside (1), olerikaside, and other known secoiridoid glucosides [oleuropein (2), demethyl oleuropein (3), oleoside 11-methyl ester (4), oleoside 7, 11-dimethyl ester (5), 7-β-D-glucopyranosyl 11-methyl oleoside (6), secoxyloganin (7), ilicifolioside B (8), hydroxytyrosol (9), and hydroxytyrosol glucosides (10–12)] were isolated from unprocessed olive fruits of Olea europaea cv. “Lucca”. The chemical structure of olerikaside (1) was clarified based on spectroscopy and chemical analysis data.
- Ishimaru, Kanji,Kotoda, Nobuhiro,Matsuo, Yosuke,Nakayama, Hideyuki,Nishi, Nanami,Tanaka, Takashi
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- Process for preparing hydroxytyrosol
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The invention discloses a process for preparing hydroxytyrosol. According to the process, benzodioxole is used as a starting material, firstly, benzodioxole and ethylene oxide are subjected to a Friedel-Crafts alkylation reaction to prepare pepper ethanol, and then the pepper ethanol is subjected to a catalytic hydrolysis reaction to prepare hydroxytyrosol. The hydroxytyrosol preparation process disclosed by the invention has the characteristics of easily available and cheap raw materials, simple operation process, safety, environmental protection and the like.
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Paragraph 0050; 0090-0098
(2021/08/19)
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- Synthesis method for hydroxytyrosol
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The invention belongs to the field of organic synthesis, and discloses a synthesis method for hydroxytyrosol. The method comprises a step b that: a reaction is carried out on 3-bromine-4-hydroxy phenylethanol, an alkali metal hydroxide and a copper catalyst, wherein the copper catalyst is at least one selected from 8-hydroxyquinoline copper, copper acetylacetonate and BFMO-cuprous iodide. According to the process route, hydroxyl protection and deprotection steps are omitted, bromine does not need to be replaced with methoxyl, hydroxyl substitution is achieved in a sodium hydroxide aqueous solution under catalysis of the copper catalyst, and therefore, selectivity is good, the reaction route is short, the product can be obtained only through two steps, and the problem that an existing process route is too long is solved.
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Paragraph 0052; 0058-0062; 0063; 0066-0067; 0068; 0071-0072
(2021/03/11)
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- Antioxidant and Biological Activities of Hydroxytyrosol and Homovanillic Alcohol Obtained from Olive Mill Wastewaters of Extra-Virgin Olive Oil Production
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Some constituents of the Mediterranean diet, such as extra-virgin olive oil (EVOO) contain substances such as hydroxytyrosol (HT) and its metabolite homovanillic alcohol (HA). HT has aroused much interest due to its antioxidant activity as a radical scavenger, whereas only a few studies have been made on the HA molecule. Both chemical synthesis and extraction techniques have been developed to obtain these molecules, with each method having its advantages and drawbacks. In this study, we report the use of tyrosol from olive mill wastewaters as a starting molecule to synthesize HT and HA, using a sustainable procedure characterized by high efficiency and low cost. The effects of HT and HA were evaluated on two cell lines, THP-1 human leukemic monocytes and L-6 myoblasts from rat skeletal muscle, after treating the cells with a radical generator. Both HT and HA efficiently inhibited ROS production. In particular, HT inhibited the proliferation of the THP-1 leukemic monocytes, while HA protected L-6 myoblasts from cytotoxicity.
- Ricelli, Alessandra,Gionfra, Fabio,Percario, Zulema,De Angelis, Martina,Primitivo, Ludovica,Bonfantini, Veronica,Antonioletti, Roberto,Bullitta, Simonetta Maria,Saso, Luciano,Incerpi, Sandra,Pedersen, Jens Zacho
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p. 15428 - 15439
(2021/01/09)
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- Method for preparing 3, 4-dihydroxyphenylethanol
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The invention discloses a method for preparing 3, 4-dihydroxyphenylethanol, which comprises the following steps: (1) preparing benzyloxymethyltriphenylphosphorus chloride, (2) preparing 3.4-dibenzyloxy benzaldehyde, (3) preparing 1, 2-dibenzyloxy-4-(2-benzyloxyvinyl)benzene, and (4) preparing 3, 4-dihydroxyphenylethanol. Compared with the prior art, the method has the advantages that 1, raw materials and reagents used in the method are lower in toxicity, safer, cheaper, easier to obtain and convenient to store, and the raw materials and operation cost are greatly reduced, 2, the method has fewreaction steps, is convenient to operate, and is easier for large-scale production, and 3, the method does not generate high-toxicity three wastes, so that the environmental pollution is reduced, andthe ecological environment is protected. Meanwhile, the yield of the prepared product is high and can reach 90% or above.
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- Synthesis of high added value compounds through catalytic oxidation of 2-phenylethanol: A Kinetic study
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An effective procedure was developed to produce high-value added phenolic compounds through the conversion of 2-phenylethanol (2-PhEt) by using acid-activated clays KSF for the hydrogen peroxide. Owing to KSF's ability to catalyze a variety of complex oxi
- Ben Hmida, Rania,Frikha, Nourzed,Bouguerra Neji, Soumaya,Kit, Geoffrey,Medina, Francisco,Bouaziz, Mohamed
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p. 124 - 133
(2019/12/03)
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- Chemoenzymatic synthesis of hydroxytyrosol monoesters and their suppression effect on nitric oxide production stimulated by lipopolysaccharides
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Fatty acid monoesters of hydroxytyrosol [2-(3,4-dihydroxyphenyl)ethanol] were synthesized in two steps from tyrosol (4-hydroxyphenylethanol) by successive Candida antarctica lipase B-catalyzed chemoselective acylation on the primary aliphatic hydroxy group over phenolic hydroxy group in tyrosol, and 2-iodoxybenzoic acid (IBX)-mediated hydroxylation adjacent to the remaining free phenolic hydroxy group. Examination of their suppression effects on nitric oxide production stimulated by lipopolysaccharides in RAW264.7 cells showed that hydroxytyrosol butyrate exhibited the highest inhibition (IC50 7.0 μM) among the tested compounds.
- Sakakura, Ayaka,Pauze, Martin,Namiki, Atsuhiro,Funakoshi-Tago, Megumi,Tamura, Hiroomi,Hanaya, Kengo,Higashibayashi, Shuhei,Sugai, Takeshi
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p. 185 - 191
(2019/02/05)
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- 3, 4-dihydroxyphenylethanol synthesis method
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An embodiment of the invention discloses a 3, 4-dihydroxyphenylethanol synthesis method which includes the steps: taking a compound I as a raw material to prepare a compound II under the action of a catalyst for standby application; performing reaction on the compound II prepared in the first step and strong acid, and extracting and concentrating a reactant to prepare a compound III; dissolving the compound III in a solvent to perform reaction under the of a catalyst to prepare a compound IV; performing diazo-reaction and acidic hydrolysis on the compound IV to generate 3, 4-dihydroxyphenylethanol. According to the 3, 4-dihydroxyphenylethanol synthesis method, raw materials are moderate in cost, mass production is easily implemented, the purity of the 3, 4-dihydroxyphenylethanol is higherthan 99%, and overall yield can reach 78% or more. The synthesis method is simple in reaction condition, special requirements for devices are omitted, the method is easily implemented in industrial production, and organic solvents can be completely recycled and reused in the whole preparation process.
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- New method for preparing high-purity hydroxytyrosol
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The invention discloses a new method for preparing high-purity hydroxytyrosol, and belongs to the technical field of medicine chemosynthesis. The method comprises the following steps: uniformly mixinglithium aluminium hydride with a solvent, and then adding 3,4- dihydroxyphenylacetic acid in batches and performing reaction, putting reaction liquid which is completely subjected to reaction at a temperature of 0 DEG C; slowly dropwise adding water and a hydrochloric acid solution; performing extraction by using ethyl acetate after dropwise addition is completed; combining organic phases, then washing the organic phases by using sodium bicarbonate water solutions, drying the organic phases by using magnesium sulfate anhydrous, performing suction filtration and removing salt, evaporating offthe solvent under reduced pressure to obtain alight yellow oily matter, that is hydroxytyrosol. The method disclosed by the invention has the advantages of easy availability of the raw materials, lowcost, simple and convenient operation, high reaction speed, high yield of a target product, and moreover, the 3,4- dihydroxyphenylacetic acid can be reduced into the hydroxytyrosol at one step, so that the high-purity hydroxytyrosol can be prepared without need of column chromatography and purification, and the high-purity hydroxytyrosol is suitable for industrial production.
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Paragraph 0059; 0060; 0062; 0063; 0064; 0065; 0066; 0067
(2019/02/04)
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- Hydrolases-mediated transformation of oleuropein into demethyloleuropein
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Phenolic compounds present in extra virgin olive oil have recently attracted considerable attention due to their pharmacological activities. Among them oleacein (3,4-DHPEA-EDA), structurally related to oleochantal (4-HPEA-EDA), is one of the most studied. 3,4-DHPEA-EDA has been synthesized through decarboxylation of demethyloleuropein catalyzed by Er(OTf)3. Demethyloleuropein is extracted from black olives drupes in very limited amounts and only in particular periods of the year. The availability of demethyloleuropein could be increased by a selective hydrolysis of the methyl ester moiety of oleuropein, a secoiridoid present in large amount in olive leaves. In this work we describe a new enzymatic method for carrying out a selective hydrolysis of oleuropein via the screening of a panel of hydrolases (lipases, esterases and proteases). Among all the enzymes tested the best results was obtained using α-chymotrypsyn from bovine pancreas as biocatalyst, thus revealing a classic example of catalytic enzyme promiscuity.
- Cariati, Luca,Oliverio, Manuela,Mutti, Francesco G.,Bonacci, Sonia,Knaus, Tanja,Costanzo, Paola,Procopio, Antonio
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p. 384 - 388
(2018/12/13)
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- Preparation method of hydroxytyrosol
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The invention relates to the technical field of medicinal chemical synthesis, in particular to a preparation method of hydroxytyrosol. The preparation method of the hydroxytyrosol comprises the following step of taking an alcohol and/or an ether as a solvent to carry out a reaction on methyl 3,4-dihydroxyphenylacetate under the action of a reducing agent and Lewis acid to obtain the hydroxytyrosol. According to the preparation method of the hydroxytyrosol, the reducing agent and the Lewis acid are matched for carrying out catalytic reducing, so that reaction activity is improved, and the product yield and purity are high. In addition, the single solvent is used, so that post-treatment is convenient, the solvent is convenient to recycle, energy consumption and material loss are reduced, andproduction cost is greatly saved.
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Paragraph 0057; 0061-0063; 0064-0089
(2019/10/01)
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- A three-step, gram-scale synthesis of hydroxytyrosol, hydroxytyrosol acetate, and 3,4-dihydroxyphenylglycol
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Hydroxytyrosol and two other polyphenols of olive tree, hydroxytyrosol acetate and 3,4-dihydroxyphenylglycol, are known for a wide range of beneficial activities in human health and prevention from diseases. The inability to isolate high, pure amounts of these natural compounds and the difficult and laborious procedures for the synthesis of them led us to describe herein an efficient, easy, cheap, and scaling up synthetic procedure, from catechol, via microwave irradiation.
- Kalampaliki, Amalia D.,Giannouli, Vassiliki,Skaltsounis, Alexios-Leandros,Kostakis, Ioannis K.
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- Improved method of hydroxytyrosol synthesizing process
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The invention discloses an improved method of a hydroxytyrosol synthesizing process. According to the method, 3, 4-dihydroxyphenylacetic acid is reduced by tetrabutylammonium borohydride to obtain hydroxytyrosol. The improved method provided by the invention achieves effects of safe and simple operation, low cost, environmental protection, less three wastes and high quality by adjusting the reaction post-treatment step.
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Paragraph 0021
(2018/07/06)
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- Hydroxytyrosol synthesizing process
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The invention relates to a hydroxytyrosol (3,4-dihydroxyphenylethanol) synthesizing process. The hydroxytyrosol (3,4-dihydroxyphenylethanol) synthesizing process comprises the steps of diazotizing andnitrifying 4-aminophenethyl alcohol, carrying out reduction, and carrying out diazotization to generate hydroxytyrosol. The method has the characteristics that the costs of raw materails are low, starting materials are easy to obtain, and the method is safe and simple to operate, and is suitable for industrial production.
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Paragraph 0007; 0021; 0026; 0027
(2019/01/14)
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- Effects of Sugars, Furans, and their Derivatives on Hydrodeoxygenation of Biorefinery Lignin-Rich Wastes to Hydrocarbons
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Hydrodeoxygenation of biorefinery lignin-rich wastes to jet fuel hydrocarbons offers a significant opportunity for enhancing the overall operational efficiency, carbon conversion efficiency, economic viability, and sustainability of biofuels production. However, these wastes usually mainly contain lignin with sugars, furans, and their derivatives as “impurities”. Although several factors, including reactant structure, solvents, or the decreased ratio of catalyst to reactant, could be responsible for the jet fuel hydrocarbons yield loss, we found evidence that glucose, xylose, and 5-hydroxymethylfurfural dramatically decreased conversion yields. For example, xylose and glucose lowered the final hydrocarbon yield by 78 and 63 %, respectively. The results revealed that these compounds could suppress metal catalysts and inhibit lignin depolymerization and hydrodeoxygenation (HDO) reactions thus decrease yields of jet fuel range hydrocarbons from biomass-derived lignin. The first-principles calculations and TGA results from spent catalysts validated these findings.
- Wang, Hongliang,Duan, Yuhua,Zhang, Qian,Yang, Bin
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p. 2562 - 2568
(2018/08/01)
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- Valorization of Oleuropein via Tunable Acid-Promoted Methanolysis
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The acid-promoted methanolysis of oleuropein was studied using a variety of homogeneous and heterogeneous acid catalysts. Exclusive cleavage of the acetal bond between the glucoside and the monoterpene subunits or further hydrolysis of the hydroxytyrosol ester and subsequent intramolecular rearrangement were observed upon identification of the most efficient catalyst and experimental conditions. Furthermore, selected conditions were tested using oleuropein under continuous flow and using a crude mixture extracted from olive leaves under batch. Formation of (?)-methyl elenolate was also observed in this study, which is a reported precursor for the synthesis of the antihypertensive drug (?)-ajmalicine.
- Cavaca, Lídia A. S.,Rodrigues, Catarina A. B.,Simeonov, Svilen P.,Gomes, Rafael F. A.,Coelho, Jaime A. S.,Romanelli, Gustavo P.,Sathicq, Angel G.,Martínez, José J.,Afonso, Carlos A. M.
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p. 2300 - 2305
(2018/07/31)
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- METHOD FOR PREPARATION OF HYDROXYTYROSOL
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The invention discloses a method for the preparation of (3,4-dihydroxyphenyl)acetic acid or its ester starting from the respective nitrile, and the conversion of (3,4-dihydroxyphenyl)acetic acid ester to hydroxytyrosol.
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Page/Page column 9
(2017/09/15)
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- The carbonate derivatives as skin care
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Carbonates of anti-aging ingredients, in particular anti-oxidants and skin illuminating phenol ingredients, have been prepared as derivatives of these ingredients with enhanced physical properties. It has been demonstrated that these carbonates will hydrolyze under enzymatic catalysis to release the parent ingredient. In contrast, esters of the phenolic groups in many cases do not hydrolyze under the same conditions.
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Paragraph 0056; 0057
(2017/02/28)
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- Kinetic and solvent isotope effects on biotransformation of aromatic amino acids and their derivatives
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Aromatic amino acids such as l-phenylalanine, l-tryptophan, 3′,4′-dihydroxy-l-phenylalanine (l-DOPA), and their derivatives 3′,4′-dihydroxyphenylacelaldehyde (DOPAL) and 3′,4′-dihydroxyphenylethanol (DOPET), play an essential role in human metabolic processes. Incorrect or slow biotransformation of these compounds leads to some metabolic dysfunctions and in some cases to some neurodegenerative diseases. Therefore, studies of the biotransformation mechanisms of these metabolites draw biochemists' and medical researchers' attention. This study investigates the mechanisms of biotransformation of the aforementioned compounds using kinetic (KIE) and solvent (SIE) isotope effect methods. The overview presents the results and the numerical values of KIE and SIE methods, obtained in the study of biotransformation of l-phenylalanine, 5′-chloro-l-tryptophan, and l-DOPA, catalyzed by the enzymes from the lyases group (phenylalanine ammonia lyase, tryptophan indole-lyase, and tyrosine decarboxylase). Deuterium KIE was also determined during the deamination of 2′-chloro-l-phenylalanine in the presence of the enzyme l-phenylalanine dehydrogenase, as well as in the conversion of DOPAL into DOPET catalyzed by the enzyme alcohol dehydrogenase. The values of KIE and SIE have been determined using a noncompetitive spectrophotometric and a competitive (combined with internal radioactivity standard) radiometric methods.
- Kańska, Marianna,Jemielity, Jacek,Paj?k, Ma?gorzata,Pa?ka, Katarzyna,Podsadni, Katarzyna,Winnicka, El?bieta
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p. 627 - 634
(2016/12/26)
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- Exploring the synthetic applicability of a new carboxylic acid reductase from Segniliparus rotundus DSM 44985
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A new carboxylic acid reductase (CAR) gene from Segniliparus rotundus DSM 44985 was overexpressed in Escherichia coli. The recombinant enzyme exhibited high activity toward a variety of aromatic and aliphatic carboxylic acids. Especially, it effectively reduced 4-hydroxybenzoic acid (8a) and 4-nitrobenzoic acid (19a), toward which the known Nocardia CAR exhibited no or little activity. The recombinant E. coli cells co-expressing the Segniliparus CAR and Nocardia PPTase genes catalyzed the reductions of vanillic acid (20a) and 3,4-dihydroxyphenylacetic acid (25a) to give vanillyl alcohol (20c) and 3-hydroxytyrosol (25c) with high yield, respectively. The endogenous aldehyde reductases of E. coli should be responsible for the further reduction of the produced aldehydes. These results demonstrated that Segniliparus CAR was a useful addition to the biocatalyst tool-box for the reduction of carboxylic acids and might find applications in the synthesis of valuable bio-based chemicals from renewable resources.
- Duan, Yitao,Yao, Peiyuan,Chen, Xi,Liu, Xiangtao,Zhang, Rui,Feng, Jinhui,Wu, Qiaqing,Zhu, Dunming
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- Compositions and methods for treating obesity, obesity related disorders and for inhibiting the infectivity of human immunodeficiency virus
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The present invention relates to methods and pharmaceutical compositions for treating obesity or obesity-related disorders in a subject suffering from or predisposed to developing obesity or an obesity-related disorder, or for inhibiting the infectivity of HIV, by administering oleuropein, an analogue or derivative thereof, or the major metabolites of oleuropein including oleuropein aglycone, hydroxytyrosol, and elenolic acid or their analogues, or derivatives thereof, an iridoid glycoside, or a secoiridoid glycoside or analogues or derivatives thereof, or any combination of the foregoing including olive leave extract. The invention also relates to methods for screening/diagnosing a subject having, or predisposed to having obesity or a related disorder by measuring the expression profiles of an adipogenic gene selected from PPARγ2, LPL and αP2 gene and gene product, or other adipogenic, lipogenic, or lipolytic genes and gene products in an individual. The invention further provides for screening for novel oleuropein analogues.
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- NOVEL DERIVATIVES OF SINAPINIC ACID AND THE COSMETIC OR PHARMACEUTICAL USES THEREOF
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The present invention relates to a compound of general formula (I) below: in which: R1, R2 and R3 independently of one another represent a hydrogen atom; a C1-12 alkyl group; a C2-12 alkenyl group; a C2-12 alkynyl group; a C3-12 cycloalkyl group; a C1-12 acyl group; a sulfonyl group or a phosphonate group; represents a CH2—CH2 group or a CH═CH group; n is an integer between 1 and 3; or a salt thereof. The invention further relates to a process for synthesizing this compound or salt, to a composition comprising it, to its cosmetic use, more particularly as a depigmenting agent and/or as a radical scavenger, to a cosmetic care process, and to its use as a drug, advantageously intended for preventing and/or treating pathological hyperpigmentation and/or inflammation.
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- HYDROXYTYROSOL DERIVATIVES, THEIR METHOD OF PREPARATION AND USE IN PERSONAL CARE
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Hydroxytyrosol derivative compositions, methods for their manufacture, and their use in personal care products are disclosed. Lipophilic hydroxytyrosol carbonate ester compound can be made by oxidizing a substituted hydroxybenzaldehyde compound with an oxidizing agent such as hydrogen peroxide under mild conditions. The process involves enzymatic esterification of 4-(2-hydroxyethyl)phenol to form the corresponding ester, the introduction of a formyl group ortho to the phenolic hydroxyl group of the ester to form a lipophilic formyltyrosol ester; oxidation of the lipophilic formyltyrosol ester with a peroxide compound to form a lipophilic hydroxytyrosol ester compound; and reaction of lipophilic hydroxytyrosol ester compound with carbonic acid ester derivatives to form a lipophilic hydroxytyrosol carbonic ester compound. These compounds are useful is a wide variety of personal care compositions as anti-aging compounds that are stable against oxidation.
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Paragraph 0200
(2015/05/13)
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- Design, synthesis and biological evaluation of small molecular polyphenols as entry inhibitors against H5N1
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To find novel compounds against H5N1, three series of known or novel small molecular polyphenols were synthesized and tested in vitro for anti-H5N1 activity. In addition, the preliminary structure-antiviral activity relationships were elaborated. The results showed that some small molecular polyphenols had better anti-H5N1 activity, and could serve as novel virus entry inhibitors against H 5N1, likely targeting to HA2 protein. Noticeably, compound 4a showed the strongest activity against H5N1 among these compounds, and the molecular modeling analysis also suggested that this compound might target to HA2 protein. Therefore, compound 4a is well qualified to serve as a lead compound or scaffold for the further development of H 5N1 entry inhibitor.
- Yang, Jian,Yang, Jing Xiang,Zhang, Fang,Chen, Gang,Pan, Wei,Yu, Rui,Wu, Shuwen,Tien, Po
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p. 2680 - 2684
(2014/06/09)
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- Method of preparation of hydroxytyrosol
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The present invention relates to a method of preparation of hydroxytyrosol from eugenol, said method comprising: - a step of oxidative cleavage, in particular in the presence of an oxidative reactant such as ozone followed by the addition in situ of a mild hydride source such as NaBH4, and - a step of demethylation, in particular in the presence of a Lewis acid, such as All3, or of an inorganic hypervalent iodine compound, such as NalO4, followed by a reductive treatment.
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Page/Page column 0064
(2013/08/15)
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- PROCESS FOR PRODUCTION OF HYDROXYTYROSOL USING ORGANOMETALLIC COMPOUNDS
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Disclosed is a process for the production of a 4-(2-hydroxyalkyl)-1,2-benzenediol, comprising the steps of (a) providing protected 1,2-benzenediol having the 1,2-hydroxyl groups protected, (b) halogenating the protected 1,2-benzenediol to obtain a protected 4-halo-1,2-benzenediol having the 1,2-hydroxyl groups protected, (c) reacting, in the presence of a metal or organometallic compound, the protected 4-halo-1,2-benzenediol to protected 4-(2-hydroxyalkyl)-1,2-benzenediol having the 1,2-hydroxyl groups protected, and (d) deprotecting the protected 4-(2-hydroxyalkyl)-1,2-benzenediol to obtain the 4-(2-hydroxyalkyl)-1,2-benzenediol. Also disclosed is the use of 1,2-benzenediol for the production of hydroxytyrosol.
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- Layer-by-Layer coated tyrosinase: An efficient and selective synthesis of catechols
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Agaricus bisporous tyrosinase was immobilized on commercial available epoxy-resin EupergitC250L and then coated by the Layer-by-Layer method (LbL). The two novel heterogeneous biocatalysts were characterized for their morphology, pH and storage stability, kinetic properties (Km, V max, Vmax/Km) and reusability. These biocatalysts were used for the efficient and selective synthesis of bioactive catechols under mild and environmental friendly experimental conditions. Ascorbic acid was added in the reaction medium to inhibit the formation of ortho-quinones, thus avoiding the known enzyme suicide inactivation process. Catechols were obtained mostly in quantitative yields and conversion of substrate. Tyrosinase immobilized on EupergitC250L and coated by the LbL method showed better catalytic activities, higher pH and storage stability, and reusability with respect to immobilized uncoated tyrosinase. Since chemical procedures to synthesize catechols are often expensive and with high environmental impact, the use of immobilized tyrosinase represents an efficient alternative for the preparation of this family of bioactive compounds.
- Guazzaroni, Melissa,Crestini, Claudia,Saladino, Raffaele
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experimental part
p. 157 - 166
(2012/02/13)
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- Efficient synthesis of hydroxytyrosol from 3,4-dihydroxybenzaldehyde
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Hydroxytyrosol is a naturally occurred orthodiphenolic component of olive oil. A variety of biological functions for this molecule have been reported. We report herein an efficient and practical method for the chemical synthesis of hydroxytyrosol from 2,3-dihydroxybenzaldehyde. Taylor & Francis Group, LLC.
- Zhang, Zhao-Li,Chen, Jinglei,Xu, Qiongming,Rao, Cui,Qiao, Chunhua
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p. 794 - 798
(2012/01/17)
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- PROCESS FOR PREPARING HYDROXYTYROSOL
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A process for preparing hydroxytyrosol from eugenol is disclosed. The eugenol can be converted to 4-(2-hydroxyethyl)-2-methoxyphenol, which is subsequently converted to hydroxytyrosol. The eugenol can also be initially demethylated, and the reaction product is subsequently converted to hydroxytyrosol. A process for producing 4-(2-hydroxyethyl)-2-methoxyphenol is also disclosed.
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Page/Page column 9
(2012/02/01)
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- An efficient, economical synthesis of hydroxytyrosol and its protected forms via Baeyer-Villiger oxidation
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An efficient and practical preparation of hydroxytyrosol and its orthogonally-protected forms was developed from inexpensive tyrosol. The utilization of Baeyer-Villiger oxidation enables the chemoselective introduction of a phenolic hydroxyl group in good yield.
- Piersanti, Giovanni,Retini, Michele,Espartero, José L.,Madrona, Andres,Zappia, Giovanni
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p. 4938 - 4940
(2011/10/07)
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- Lipophilic hydroxytyrosol esters: Fatty acid conjugates for potential topical administration
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Hydroxytyrosol is a potent antioxidant natural molecule isolated from olive leaves and fruits. The presence of three hydroxy groups in its structure poses a limit for the topical application of this lead compound. A set of hydroxytyrosol conjugates with fatty acids at different molecular weights were synthesized under mild conditions. The topical delivery features of this new set of antioxidant molecules were evaluated as a function of their permeation profiles through the human stratum corneum and viable epidermis membranes. A dependence on their partition coefficients, their molecular weights, and their isometric configurations was then postulated. Encouraging results prompt further investigations on the polyfunctional role that hydroxytyrosol conjugates could have as agents in both anti-inflammatory and antioxidant therapies.
- Procopio, Antonio,Celia, Christian,Nardi, Monica,Oliverio, Manuela,Paolino, Donatella,Sindona, Giovanni
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experimental part
p. 2377 - 2381
(2012/01/15)
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- Hypervalent iodine-mediated oxygenative phenol dearomatization reactions
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Both λ3- and λ5-iodanes have proven to be useful reagents in the oxygenative dearomatization of phenols, and exploitations of their chemistry in the conception of both substrate- and reagent-controlled asymmetric variants of such a transformation of great value for natural product synthesis have shown evident signs of success. Moreover, the use of stabilized IBX (i.e., SIBX) in our methodology for O-demethylation of 2-methoxyphenols, which relies on the same key oxygenating dearomatization event, is reported here to be much more efficacious than that of IBX itself in the chemoselective one-step conversion of homovanillyl alcohol into hydroxytyrosol, and bergenin into norbergenin.
- Pouységu, Laurent,Sylla, Tahiri,Garnier, Tony,Rojas, Luis B.,Charris, Jaime,Deffieux, Denis,Quideau, Stéphane
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experimental part
p. 5908 - 5917
(2010/09/09)
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- PROCESS FOR STRAIGHTENING KERATIN FIBRES WITH A HEATING MEANS AND DENATURING AGENTS
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The invention relates to a process for straightening keratin fibres, comprising: (i) a step in which a straightening composition containing at least two denaturing agents is applied to the keratin fibres, (ii) a step in which the temperature of the keratin fibres is raised, using a heating means, to a temperature of between 110 and 250° C.
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- A novel use of the recyclable polymer-supported IBX: an efficient chemoselective and regioselective oxidation of phenolic compounds. The case of hydroxytyrosol derivatives.
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A useful and novel application of polymer-supported IBX for the chemoselective and regioselective oxidation of phenolic compounds has been described. Hydroxytyrosol and carboxymethylated hydroxytyrosol have been prepared in good conversions and yields und
- Bernini, Roberta,Mincione, Enrico,Crisante, Fernanda,Barontini, Maurizio,Fabrizi, Giancarlo
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body text
p. 1307 - 1310
(2009/06/28)
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