- Informed Molecular Design of Conjugated Oligoelectrolytes To Increase Cell Affinity and Antimicrobial Activity
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Membrane-intercalating conjugated oligoelectrolytes (COEs) are emerging as potential alternatives to conventional, yet increasingly ineffective, antibiotics. Three readily accessible COEs, belonging to an unreported series containing a stilbene core, namely D4, D6, and D8, were designed and synthesized so that the hydrophobicity increases with increasing side-chain length. Decreased aqueous solubility correlates with increased uptake by E. coli. The minimum inhibitory concentration (MIC) of D8 is 4 μg mL?1 against both E. coli and E. faecalis, with an effective uptake of 72 %. In contrast, the MIC value of the shortest COE, D4, is 128 μg mL?1 owing to the low cellular uptake of 3 %. These findings demonstrate the application of rational design to generate efficacious antimicrobial COEs that have potential as low-cost antimicrobial agents.
- Zhou, Cheng,Chia, Geraldine W. N.,Ho, James C. S.,Seviour, Thomas,Sailov, Talgat,Liedberg, Bo,Kjelleberg, Staffan,Hinks, Jamie,Bazan, Guillermo C.
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- Gemini surfactants: A new class of self-assembling molecules
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"Gemini surfactant" is a name assigned to a family of synthetic amphiphiles possessing, in sequence, a long hydrocarbon chain, an ionic group, a spacer, a second ionic group, and another hydrocarbon tail. Intramolecular chain/chain association was inhibited through the use of rigid spacers, thereby averting self-assembly into conventional micellar structures. Aggregation of the geminis was investigated by (a) surface tension, (b) film-balance methods, (c) dynamic light scattering, (d) 1H and 23Na NMR, and (e) spectral changes in an adsorbed dye. Among the more striking properties of geminis, one should cite the following: (a) a higher critical micelle concentration (according to surface tension and NMR) for geminis with two long chains of 16-20 carbons than that for shorter-chain analogs; (b) the lift-off areas in monomolecular films that are several times those of phospholipids, indicating that the geminis lie absolutely horizontally at the air/water interface; and (c) the formation of only small micelles, despite the potential to grow, polymer-like, into extended strands. It is argued that geminis, especially the longer-chain members, engage in self-coiling or submicellar aggregation when first exposed to water. Self-assembly into micelles and adsorption at the air/water interface then take place over hours or days at 23 °C but much more rapidly at 50 °C. Spectral data provide strong evidence for submicellar structures.
- Menger,Littau
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- Selective synthesis of the resveratrol analogue 4,4′-dihydroxy-: Trans -stilbene and stilbenoids modification by fungal peroxygenases
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This work gives first evidence that the unspecific peroxygenases (UPOs) from the basidiomycetes Agrocybe aegerita (AaeUPO), Coprinopsis cinerea (rCciUPO) and Marasmius rotula (MroUPO) are able to catalyze the regioselective hydroxylation of trans-stilbene to 4,4′-dihydroxy-trans-stilbene (DHS), a resveratrol (RSV) analogue whose preventive effects on cancer invasion and metastasis have very recently been shown. Nearly complete transformation of substrate (yielding DHS) was achieved with the three enzymes tested, using H2O2 as the only co-substrate, with AaeUPO showing exceptionally higher total turnover number (200000) than MroUPO (26000) and rCciUPO (1400). Kinetic studies demonstrated that AaeUPO was the most efficient enzyme catalyzing stilbene dihydroxylation with catalytic efficiencies (kcat/Km) one and two orders of magnitude higher than those of MroUPO and rCciUPO, so that 4-hydroxystilbene appears to be the best UPO substrate reported to date. In contrast, the peroxygenase from the ascomycete Chaetomium globosum (CglUPO) failed to hydroxylate trans-stilbene at the aromatic ring and instead produced the trans-epoxide in the alkenyl moiety. In addition, stilbenoids such as pinosylvin (Pin) and RSV were tested as substrates for the enzymatic synthesis of RSV from Pin and oxyresveratrol (oxyRSV) from both RSV and Pin. Overall, lower conversion rates and regioselectivities compared with trans-stilbene were accomplished by three of the UPOs, and no conversion was observed with CglUPO. The highest amount of RSV (63% of products) and oxyRSV (78%) were again attained with AaeUPO. True peroxygenase activity was demonstrated by incorporation of 18O from H218O2 into the stilbene hydroxylation products. Differences in the number of phenylalanine residues at the heme access channels seems related to differences in aromatic hydroxylation activity, since they would facilitate substrate positioning by aromatic-aromatic interactions. The only ascomycete UPO tested (that of C. globosum) turned out to have the most differing active site (distal side of heme cavity) and reactivity with stilbenes resulting in ethenyl epoxidation instead of aromatic hydroxylation. The above oxyfunctionalizations by fungal UPOs represent a novel and simple alternative to chemical synthesis for the production of DHS, RSV and oxyRSV.
- Aranda, Carmen,Ullrich, René,Kiebist, Jan,Scheibner, Katrin,Del Río, José C.,Hofrichter, Martin,Martínez, Angel T.,Gutiérrez, Ana
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- Two resveratrol analogs, pinosylvin and 4,4′-dihydroxystilbene, improve oligoasthenospermia in a mouse model by attenuating oxidative stress via the Nrf2-ARE pathway
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Two synthesized resveratrol analogs from our laboratory, namely pinosylvin (3,5-dihydroxy-trans-stilbene, PIN) and 4,4′-dihydroxystilbene (DHS), have been carefully evaluated for treatment of oligoasthenospermia. Recent studies have demonstrated that PIN and DHS improved sperm quality in the mouse. However, the mechanism of action of PIN and DHS on oligoasthenospermia remains unknown. Herein, we investigated the mechanistic basis for improvements in sperm parameters by PIN and DHS in a mouse model of oligoasthenospermia induced by treatment with busulfan (BUS) at 6 mg/kg b.w. Two weeks following busulfan treatment, mice were administered different concentrations of PIN or DHS daily for 2 consecutive weeks. Thereafter, epididymal sperm concentration and motility were determined, and histopathology of the testes was performed. Serum hormone levels including testosterone (T), luteinizing hormone (LH), and follicle stimulating hormone (FSH) were measured using corresponding specific enzyme-linked immunosorbent assay (ELISA) kits. Testicular mRNA expression profiles were determined by RNA sequencing analysis. These findings were validated by quantitative real-time PCR, western blotting and ELISA. Both PIN and DHS improved the epididymal sperm concentration and motility, enhanced testosterone levels, and promoted testicular morphological recovery following BUS treatment. PIN treatment was found to significantly reduce oxidative stress via the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE)-dependent antioxidant, glutathione peroxidase 3. DHS treatment significantly reduced oxidative stress via the Nrf2-ARE-dependent antioxidants glutathione S-transferase theta 2 and glutathione S-transferase omega 2. In summary, PIN and DHS ameliorated oligoasthenospermia in this mouse model by attenuating oxidative stress via the Nrf2-ARE pathway.
- Cheng, C. Yan,Gong, Sheng-nan,Sang, Meng-meng,Sun, Fei,Wang, Cheng-niu,Yang, Jin-fei
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- A Bisphenolic Honokiol Analog Outcompetes Oral Antimicrobial Agent Cetylpyridinium Chloride via a Membrane-Associated Mechanism
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Targeting Streptococcus mutans is the primary focus in reducing dental caries, one of the most common maladies in the world. Previously, our groups discovered a potent bactericidal biaryl compound that was inspired by the natural product honokiol. Herein, a structure activity relationship (SAR) study to ascertain structural motifs key to inhibition is outlined. Furthermore, mechanism studies show that bacterial membrane disruption is central to the bacterial growth inhibition. During this process, it was discovered that analog C2 demonstrated a 4-fold better therapeutic index compared to the commercially available antimicrobial cetylpyridinium chloride (CPC) making it a viable alternative for oral care.
- Ochoa, Cristian,Solinski, Amy E.,Nowlan, Marcus,Dekarske, Madeline M.,Wuest, William M.,Kozlowski, Marisa C.
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- LIQUID CRYSTAL MIXTURE AND LIQUID CRYSTAL DISPLAY
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The invention relates to a compound of formula (I), wherein R11, R21, A11, A, Z, X11, X21, Y11, Y12, Sp11, Sp21, o and p have one of the meanings as given in claim 1. The invention further relates to method of production of a compound of formula (I), to the use of said compounds in LC media and to LC media comprising one or more compounds of formula (I). Further, the invention relates to a method of production of such LC media, to the use of such media in LC devices, and to LC device comprising a LC medium according to the present invention.The present invention further relates to a process for the fabrication such liquid crystal display and to the use of the liquid crystal mixtures according to the invention for the fabrication of such liquid crystal display.
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(2020/12/29)
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- Ligand-controlled iridium-catalyzed semihydrogenation of alkynes with ethanol: highly stereoselective synthesis of E- and Z-alkenes
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A ligand-controlled iridium-catalyzed semihydrogenation of alkynes to E- and Z-alkenes with ethanol was developed. Effective selectivity control was achieved by ligand regulation. The use of 1,2-bis(diphenylphosphino)ethane (DPPE) and 1,5-cyclooctadiene (COD) was critical for the stereoselective semihydrogenation of alkynes. The general applicability of this procedure was highlighted by the synthesis of more than 40 alkenes, with good stereoselectivities. The value of our approach in practical applications was investigated by studying the effects of pinosylvin and 4,4′-dihydroxystilbene (DHS) on zebrafish as a vertebrate model.
- Yang., Jinfei,Wang, Chengniu,Sun, Yufeng,Man, Xuyan,Li, Jinxia,Sun, Fei
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p. 1903 - 1906
(2019/05/02)
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- Galloyl esters of trans-stilbenes are inhibitors of FASN with anticancer activity on non-small cell lung cancer cells
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Fatty acid synthase (FASN) is a lipogenic enzyme that is selectively upregulated in malignant cells. There is growing consensus on the oncogenicity of FASN-driven lipogenesis and the potential of FASN as a druggable target in cancer. Here, we report the synthesis and FASN inhibitory activities of two novel galloyl esters of trans-stilbene EC1 and EC5. Inhibition of FASN was accompanied by a loss in AKT activation and profound apoptosis in several non-small cell lung cancer (NSCLC) cells at the growth inhibitory concentrations of EC1 and EC5. Both FASN and phospho-AKT levels were concurrently downregulated. However, addition of a lipid concentrate to the treated cells reinstated cell viability and reversed the loss of FASN and AKT protein levels, thus recapitulating the causal relationship between FASN inhibition and the loss in cell viability.
- Tan, Yu-Jia,Ali,Tee, Sheng-Yang,Teo, Jun-Ting,Xi, Yu,Go, Mei-Lin,Lam
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- CONJUGATED OLIGOELECTROLYTES AS ANTIMICROBIAL AGENTS
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Disclosed herein are compounds of formula I, where said compounds displays antibacterial properties. Also disclosed herein is the use of said compounds to treat microbial infection. The compounds of formula I have the following structure:, where n, m, p, q, X, R1 to R11 are as defined herein.
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(2019/11/12)
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- Facile utilisation of aldehyde bisulfite adducts: Synthesis of (E)-1,2- diphenylethenes
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Background: A one-pot coupling reaction of aldehyde bisulfite adducts was developed for McMurry reaction using Zn-TiCl4 in 1,4-dioxane solvent medium. The treatment of sodium hydroxy(phenyl)methane sulfonate (2a) with TiCl4 in 1,4-dioxane favoured the deprotection of the bisulfite adduct 2a, and the in situ regeneration of benzaldehyde (1a) underwent reductive coupling to afford stilbene 3a in a relatively good yield, thus leading to an improved synthesis of a series of (E)-1,2- diphenylethenes 3. The present approach provides a new solution to the inherent instability of aldehydes and also provides a direct access to C'C bond formation for the synthesis of 1,2-diphenylethenes from aryl aldehyde bisulfite adducts. Methods: All reactions were performed at 70-80o and the synthesized compounds were characterized by IR, 1H NMR, 13C NMR, and mass spectrometric techniques. Results: The present approach provides a new solution to the instability of aldehydes and also provides a direct access to C'C bond formation for the synthesis of 1,2-diphenylethenes from aryl aldehyde bisulfite adducts. Conclusion: In the present work, we have reported an efficient method for the synthesis of 1,2- diphenylethene derivatives. Aldehydes are commonly used as the starting materials in the McMurry reaction, which affords the stilbene derivatives, the core skeleton of various valuable compounds. To increase the stability of the aldehydes, bisulfite adducts are usually employed, but the deprotection process causes loss of process efficiency. To address this issue, we developed a method based on the single-pot reaction of aromatic bisulfite adduct using TiCl4/Zn in 1,4-dioxane.
- Vinay Kumar,Jaganmohan,Sandeep Reddy,Mohanty, Sandeep,Kumar, Jaydeep,Rao, Venkateswara
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p. 109 - 114
(2017/04/03)
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- Regioselective Hydroxylation of Stilbenes by Engineered Cytochrome P450 from Thermobifida fusca YX
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Since the past decades, the plant stilbenoid resveratrol has gained significant attention of the general public as well as the research community due to its versatile medicinal properties. Apart from resveratrol, there is also an increasing interest in other plant stilbenoids because of their different potential biological activities. In order to meet the increasing demand for stilbenoids, alternative and sustainable approaches for their production are needed. We identified the cytochrome P450 monooxygenase 154E1 from Thermobifida fusca YX (CYP154E1) which enables the synthesis of (E)-4,4′-dihydroxystilbene via direct double hydroxylation of (E)-stilbene. The construction of a triple mutant led to a more than six-fold increased catalytic efficiency compared to the wild type enzyme. CYP154E1 and variants thereof accepted not only (E)-stilbene but also possessed remarkable activity towards ortho- and meta-substituted hydroxystilbenes leading to resveratrol, (E)-2,4′-dihydroxystilbene, (E)-2,4′,5-trihydroxystilbene and (E)-3,4′-dihydroxystilbene. The combination of protein engineering and the use of methyl-β-cyclodextrin as substrate solubilizing agent resulted in product titers of up to 4.2 g L?1 and enzyme total turnover numbers (TTN) of up to 20,000. (Figure presented.).
- Rühlmann, Ansgar,Antovic, Dragutin,Müller, Thomas J. J.,Urlacher, Vlada B.
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p. 984 - 994
(2017/03/27)
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- A facile and rapid access to resveratrol derivatives and their radioprotective activity
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A facile and rapid access to resveratrol derivatives has been achieved based on palladium-catalyzed oxidative Heck reaction of aryl boronic acids with styrenes followed by demethylation in moderate to good yields. A series of resveratrol derivatives with various functional groups has been synthesized easily. The radioprotective activity of synthesized compounds has also been evaluated using rat thymocytes. The results revealed that some resveratrol derivatives efficiently protected the thymocytes from radiation-induced apoptosis.
- Uzura, Saori,Sekine-Suzuki, Emiko,Nakanishi, Ikuo,Sonoda, Motohiro,Tanimori, Shinji
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supporting information
p. 3886 - 3891
(2016/08/01)
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- TRPA1 channels as targets for resveratrol and related stilbenoids
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A series of twenty resveratrol analogues was synthesized and tested on TRPA1 and TRPV1 channels. None was able to significantly modulate TRPV1 channels. Conversely, most of them exhibited remarkably higher TRPA1 modulating activity than resveratrol. Optimal potency was observed with ortho monoxygenated stilbenes 6 and 17.
- Nalli, Marianna,Ortar, Giorgio,Moriello, Aniello Schiano,Morera, Enrico,Di Marzo, Vincenzo,De Petrocellis, Luciano
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p. 899 - 902
(2016/05/24)
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- A One-Pot Cascade Reaction Combining an Encapsulated Decarboxylase with a Metathesis Catalyst for the Synthesis of Bio-Based Antioxidants
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The combination of enzymes with traditional chemical catalysts unifies the high selectivity of the former with the versatility of the latter. A major challenge of this approach is the difference in the optimal reaction conditions for each catalyst type. In this work, we combined a cofactor-free decarboxylase with a ruthenium metathesis catalyst to produce high-value antioxidants from bio-based precursors. As suitable ruthenium catalysts did not show satisfactory activity under aqueous conditions, the reaction required the use of an organic solvent, which in turn significantly reduced enzyme activity. Upon encapsulation of the decarboxylase in a cryogel, the decarboxylation could be conducted in an organic solvent, and the recovery of the enzyme after the reaction was facilitated. After an intermediate drying step, the subsequent metathesis in pure organic solvent proved to be straightforward. The synthetic utility of the cascade was demonstrated by the synthesis of the antioxidant 4,4′-dihydroxystilbene in an overall yield of 90 %.
- Gómez Baraibar, álvaro,Reichert, Dennis,Mügge, Carolin,Seger, Svenja,Gr?ger, Harald,Kourist, Robert
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p. 14823 - 14827
(2016/11/23)
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- Hydroxylated di- and tri-styrylbenzenes, a new class of antiplasmodial agents: Discovery and mechanism of action
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The first systematic evaluation of the antiplasmodial activity of the hydroxystilbene family of natural products and di/tristyrylbenzenes is described. A library of 27 diversely substituted hydroxy stilbenoids was rapidly synthesized using modified Knoevenagel-Perkin-decarboxylation-Heck sequences from readily available starting materials (i.e. hydroxybenzaldehyde-phenylacetic acid-arylhalide). These compounds were evaluated for in vitro antiplasmodial activity against three different strains of Plasmodium falciparum. Notably, 4,4′4′′-((1E,1′E,1′′E)-benzene-1,3,5-triyltris(ethene-2,1-diyl))tris(2,6-dimethoxyphenol) (27), an octupolar stilbenoid, showed IC50 (μM) values of 0.6, 0.5 and 1.36 while a distyrylbenzene (11) showed IC50 values of 0.9, 2.0 and 2.7 against 3D7 (chloroquine sensitive), Dd2 and Indo (chloroquine resistant) strains of Plasmodium falciparum respectively. Moreover, 27 and 11, which exhibited selectivity indices of 40 and >111 were also found to be nontoxic to the HeLa cell line. Microscopic studies revealed that the rings and trophozoites obtained from the 27 and 11 (an octupolar tristyrylbenzene and distyrylbenzene respectively) treated cultures were growth inhibited and morphologically deformed. These cultures also showed DNA fragmentation and loss of mitochondrial membrane potential (ΔΨm), suggestive of apoptotic death of the parasite. Together, these studies introduce di/tristyrylbenzenes as a new class of antimalarial agents.
- Sharma, Naina,Mohanakrishnan, Dinesh,Shard, Amit,Sharma, Abhishek,Sinha, Arun K.,Sahal, Dinkar
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p. 49348 - 49357
(2016/07/06)
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- Inhibitory effect of cytotoxic stilbenes related to resveratrol on the expression of the VEGF, hTERT and c-Myc genes
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A group of thirty-nine stilbene derivatives, prepared by means of Heck coupling reactions, has been investigated for their cytotoxicity, as well as for their ability to inhibit the production of the vascular endothelial growth factor (VEGF) and the activation of telomerase. The ability of these compounds to inhibit proliferation of two tumoral cell lines (HT-29 and MCF-7) and one non tumoral cell line (HEK-293) was first determined. Subsequently, we determined the capacity of the compounds to inhibit the secretion of VEGF in the aforementioned cell lines and to downregulate the expression of the VEGF, hTERT and c-Myc genes, the two latter involved in the control of the activation of telomerase. One of the synthetic stilbenes, (E)-4-(4-methoxystyryl)aniline, showed strong cytotoxicity and proved able to cause a marked decrease both in the secretion of VEGF and in the expression of the hTERT and c-Myc genes, in all cases at concentrations in the low nanomolar range.
- Martí-Centelles, Rosa,Falomir, Eva,Murga, Juan,Carda, Miguel,Marco, J. Alberto
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supporting information
p. 488 - 496
(2015/10/05)
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- Aerobic oxidative coupling of resveratrol and its analogues by visible light using mesoporous graphitic carbon nitride (mpg-C3N4) as a bioinspired catalyst
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The first aerobic oxidative coupling of resveratrol and its analogues by mesoporous graphitic carbon nitride as a bioinspired catalyst with visible light has been developed. With this method, δ-viniferin and its analogues were synthesized in moderate to high yield. The metal-free conditions, visible-light irradiation, and the ideal oxidant, molecular oxygen, make this coupling reaction environmental friendly and practical. Copyright
- Song, Tao,Zhou, Bo,Peng, Guang-Wei,Zhang, Qing-Bao,Wu, Li-Zhu,Liu, Qiang,Wang, Yong
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supporting information
p. 678 - 682
(2014/01/23)
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- Extraordinary radical scavengers: 4-mercaptostilbenes
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In the past decade, there was a great deal of interest and excitement in developing more active antioxidants and cancer chemoprevention agents than resveratrol, a naturally occurring stilbene. In this work, eight resveratrol-directed 4-mercaptostilbenes were constructed based on the inspiration that thiophenol should be a stronger radical scavenger than phenol, and their reaction rates with galvinoxyl (GO.) and 2,2-diphenyl-1-picrylhydrazyl (DPPH.) radicals in methanol and ethyl acetate were measured by using stopped-flow UV/Vis spectroscopy at 25 °C. Kinetic analysis demonstrates that 4-mercaptostilbenes are extraordinary radical scavengers, and the substitution of the 4-SH group for the 4-OH group in the stilbene scaffold is an important strategy to improve the radical-scavenging activity of resveratrol. Surprisingly, in methanol, some of the 4-mercaptostilbenes are 104-times more active than resveratrol, dozens of times to hundreds of times more effective than known antioxidants (α-tocopherol, ascorbic acid, quercetin, and trolox). The detailed radical-scavenging mechanisms were discussed based on acidified-kinetic analysis. Addition of acetic acid remarkably reduced the GO. and DPPH. radical-scavenging rates of the 4-mercaptostilbenes in methanol, a solvent that supports ionization, suggesting that the reactions proceed mainly through a sequential proton loss electron transfer mechanism. In contrast, an interesting acid-promoted kinetics was observed for the reactions of the 4-mercaptostilbenes with DPPH. in ethyl acetate, a solvent that weakly supports ionization. The increased ratio in rates is closely correlated with the electron-rich environment in the molecules, suggesting that the acceleration could benefit from the contribution of the electron transfer from the 4-mercaptostilbenes and DPPH.. However, the addition of acetic acid had no influence on the GO.-scavenging rates of the 4-mercaptostilbenes in ethyl acetate, due to the occurrence of the direct hydrogen atom transfer. Our results show that the radical-scavenging activity and mechanisms of 4-mercaptostilbenes depends significantly on the molecular structure and acidity, the nature of the attacking radical, and the ionizing capacity of the solvent. Copyright
- Cao, Xiao-Yan,Yang, Jie,Dai, Fang,Ding, De-Jun,Kang, Yan-Fei,Wang, Fu,Li, Xiu-Zhuang,Liu, Guo-Yun,Yu, Sha-Sha,Jin, Xiao-Ling,Zhou, Bo
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scheme or table
p. 5898 - 5905
(2012/06/30)
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- Tandem heck/decarboxylation/heck strategy: Protecting-group-free synthesis of symmetric and unsymmetric hydroxylated stilbenoids
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Ride the (micro)wave: The title strategy has been developed for the synthesis of various symmetric or unsymmetric hydroxylated stilbenoids utilizing 4-halophenols and acrylic acid as coupling partners (see scheme; DMA=N,N-dimethylacetamide, MW=microwave). Protecting groups are not necessary and a single palladium catalyst is used. Copyright
- Shard, Amit,Sharma, Naina,Bharti, Richa,Dadhwal, Sumit,Kumar, Rajesh,Sinha, Arun K.
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supporting information
p. 12250 - 12253
(2013/02/22)
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- Identification of novel SAR properties of the Jak2 small molecule inhibitor G6: Significance of the para-hydroxyl orientation
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In this study, we analyzed the structure-activity relationship properties of the small molecule Jak2 inhibitor G6. We synthesized a set of derivatives containing the native para-hydroxyl structure or an alternative meta-hydroxyl structure and examined their Jak2 inhibitory properties. We found that the para-hydroxyl derivative known as NB15 had excellent Jak2 inhibitory properties in silico, in vitro, and ex vivo when compared with meta-hydroxyl derivatives. These results indicate that NB15 is a potent derivative of the Jak2 inhibitor G6, and that maintaining the para-hydroxyl orientation of G6 is critical for its Jak2 inhibitory potential.
- Baskin, Rebekah,Gali, Meghanath,Park, Sung O.,Zhao, Zhizhuang Joe,Keser, Gy?rgy M.,Bisht, Kirpal S.,Sayeski, Peter P.
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supporting information; experimental part
p. 1402 - 1407
(2012/04/04)
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- KINASE INHIBITOR COMPOUNDS
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The disclosure relates to novel compounds that are capable of modulating Jak2 kinase activities, compounds that have therapeutic use in treating or preventing a subject suffering from or susceptible to a Jak2 mediated disease or disorder, and methods of use and compositions thereof.
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Page/Page column 40; 74-75
(2010/07/02)
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- Phenolic bis-styrylbenzenes as β-amyloid binding ligands and free radical scavengers
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Starting from bisphenolic bis-styrylbenzene DF-9 (4), β-amyloid (Aβ) binding affinity and specificity for phenolic bis-styrylbenzenes, monostyrylbenzenes, and alkyne controls were determined by fluorescence titration with β-amyloid peptide Aβ1-40 and a fluorescence assay using APP/PS1 transgenic mouse brain sections. Bis-styrylbenzene SAR is derived largely from work on symmetrical compounds. This study is the first to describe Aβ binding data for bis-styrylbenzenes unsymmetrical in the outer rings. With one exception, binding affinity and specificity were decreased by adding and/or changing the substitution pattern of phenol functional groups, changing the orientation about the central phenyl ring, replacing the alkene with alkyne bonds, or eliminating the central phenyl ring. The only compound with an Aβ binding affinity and specificity comparable to 4 was its 3-hydroxy regioisomer 8. Like 4, 8 crossed the blood-brain barrier and bound to Aβ plaques in vivo. By use of a DPPH assay, phenol functional groups with para orientations seem to be a necessary, but insufficient, criterion for good free radical scavenging properties in these compounds.
- Flaherty, Daniel P.,Kiyota, Tomomi,Dong, Yuxiang,Ikezu, Tsuneya,Vennerstrom, Jonathan L.
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p. 7992 - 7999
(2011/03/19)
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- Weakening C-O bonds: Ti(III), a new reagent for alcohol deoxygenation and carbonyl coupling olefination
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Investigations detailed herein, including density functional theory (DFT) calculations, demonstrate that the formation of either alkoxy- or hydroxy-Ti(III) complexes considerably decreases the energy of activation for C-O bond homolysis. As a consequence of this observation, we described two new synthetic applications of Nugent's reagent in organic chemistry. The first of these applications is an one-step methodology for deoxygenation-reduction of alcohols, including benzylic and allylic alcohols and 1,2-dihydroxy compounds. Additionally, we have also proved that Ti(III) is capable of mediating carbonyl coupling-olefination. In this sense, and despite the fact that for over 35 years it has been widely accepted that either Ti(II) or Ti(0) was the active species in the reductive process of the McMurry reaction, the mechanistic evidence presented proves the involvement of Ti(III) pinacolates in the deoxygenation step of the herein described Nugent's reagent-mediated McMurry olefination. This observation sheds some light on probably one of the mechanistically more complex transformations in organic chemistry. Finally, we have also proved that both of these processes can be performed catalytically in Cp 2TiCl2 by using trimethylsilyl chloride (TMSCl) as the final oxygen trap.
- Dieguez, Horacio R.,Lopez, Armando,Domingo, Victoriano,Arteaga, Jesus F.,Dobado, Jose A.,Herrador, M. Mar,Quilez Del Moral, Jose F.,Barrero, Alejandro F.
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supporting information; experimental part
p. 254 - 259
(2010/03/25)
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- Radical-scavenging activity and mechanism of resveratrol-oriented analogues: Influence of the solvent, radical, and substitution
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(Chemical Equation Presented). Resveratrol (3,5,4′-trihydroxy-trans- stilbene, 3,5,4′-THS) is a well-known natural antioxidant and cancer chemopreventive agent that has attracted much interest in the past decade. To find a more active antioxidant and investigate the antioxidative mechanism with resveratrol as the lead compound, we synthesized 3,5-dihydroxy-trans-stilbene (3,5-DHS), 4-hydroxy-trans-stilbene (4-HS) 3,4-dihydroxy-trans-stilbene (3,4-DHS), 4,4′-dihydroxy-trans-stilbene (4,4′-DHS), 4-hydroxy-3-methoxy-trans-stilbene (3-MeO-4-HS), 4-hydroxy-4′-methoxy- trans-stilbene (4′-MeO-4-HS), 4-hydroxy-4′-methyl-trans-stilbene (4′-Me-4-HS), 4-hydroxy-4′-nitro-trans-stilbene (4′-NO 2-4-HS), and 4-hydroxy-4′-trifluoromethyl-trans-stilbene (4′-CF3-4-HS). The radical-scavenging activity and detailed mechanism of resveratrol and its analogues (ArOHs) were investigated by the reaction kinetics with galvinoxyl (GO?) and 2,2-diphenyl-1- picrylhydrazyl (DPPH?) radicals in ethanol and ethyl acetate at 25°C, using UV-vis spectroscopy. It was found that the reaction rates increase with increasing the electron-rich environment in the molecules, and the compound bearing o-dihydroxyl groups (3,4-DHS) is the most reactive one among the examined resveratrol analogues. The effect of added acetic acid on the measured rate constant for GO?-scavenging reaction reveals that in ethanol that supports ionization solvent besides hydrogen atom transfer (HAT), the kinetics of the process is partially governed by sequential proton loss electron transfer (SPLET). In contrast to GO?, DPPH ? has a relatively high reduction potential and therefore enhances the proportion of SPLET in ethanol. The relatively low rate constants for the reactions of ArOHs with GO? or DPPH? in ethyl acetate compared with the rate constants in ethanol prove that in ethyl acetate these reactions occur primarily by the HAT mechanism. The contribution of SPLET and HAT mechanism depends on the ability of the solvent to ionize ArOH and the reduction potential of the free radical involved. Furthermore, the fate of the ArOH-derived radicals, i.e., the phenoxyl radicals, was investigated by the oxidative product analysis of ArOHs and GO? in ethanol. The major products were dihydrofuran dimers in the case of resveratrol, 4,4′-DHS, and 4-HS and a dioxane-like dimer in the case of 3,4-DHS. It is suggested from the oxidative products of these ArOHs that the hydroxyl group at the 4-position is much easier to subject to oxidation than other hydroxyl groups, and the dioxane-like dimer is formed via an o-quinone intermediate.
- Shang, Ya-Jing,Qian, Yi-Ping,Liu, Xiao-Da,Dai, Fang,Shang, Xian-Ling,Jia, Wen-Qiang,Liu, Qiang,Fang, Jian-Guo,Zhou, Bo
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supporting information; experimental part
p. 5025 - 5031
(2009/10/17)
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- Laccase-catalyzed dimerization of hydroxystilbenes
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A series of hydroxystilbenes, analogues of the bioactive phytoalexin resveratrol, were synthesized and submitted to the catalytic action of a laccase from Trametes pubescens in a biphasic system made of ethyl acetate and acetate buffer. Oxidation took place at the 4′-hydroxy (4-hydroxy) position of the hydroxystilbenic moieties, followed by radical-radical coupling dimerization reactions. Most of the products were isolated in good yields and fully characterized. Depending on the substrates, three different dimeric products could be identified, the main products usually being 4-O-α-β-5 (dihydrofuran-like) dimers.
- Ponzoni, Chiara,Beneventi, Elisa,Cramarossa, Maria Rita,Raimondi, Stefano,Trevisi, Giulia,Pagnoni, Ugo Maria,Riva, Sergio,Forti, Luca
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p. 1497 - 1506
(2008/09/17)
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- An unusual, mild and convenient one-pot two-step access to (E)-stilbenes from hydroxy-substituted benzaldehydes and phenylacetic acids under microwave activation: a new facet of the classical Perkin reaction
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A mild and convenient one-pot two-step synthesis of hydroxystilbenes with trans selectivity has been developed through a modified Perkin reaction between benzaldehydes and phenylacetic acids bearing 4- or 2-hydroxy substitution at the aromatic ring, in the presence of piperidine-methylimidazole and polyethylene glycol under microwave irradiation. The observation of a simultaneous condensation-decarboxylation leading to the unusual formation of hydroxystilbenes in lieu of α-phenylcinnamic acid reveals an interesting facet to the classical Perkin reaction. The developed protocol provides a green alternative to the prevalent methods employing a toxic decarboxylating agent in the form of quinoline/Cu salt, and the requirement for harsh protection-deprotection steps for the synthesis of hydroxylated stilbenes.
- Sinha, Arun K.,Kumar, Vinod,Sharma, Abhishek,Sharma, Anuj,Kumar, Rakesh
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p. 11070 - 11077
(2008/02/12)
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- A facile and catalytic method for selective deprotection of tert-butyldimethylsilyl ethers with copper(II) bromide
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Copper(II) bromide is found to be a simple and efficient catalyst for selective deprotection of tert-butyldimethylsilyl ethers of alcohols/phenols at ambient temperature. Various labile functional groups such as ketal, alkene, ketone, OTBDPS, OTHP and allyl and benzyl ethers are found to be compatible under the reaction conditions.
- Bhatt, Suchitra,Nayak, Sandip K.
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p. 8395 - 8399
(2007/10/03)
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- Reductive olefination of aldehydes via chromium brook rearrangement
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The combination of CrCl2 and silyl chlorides converts aryl and conjugated aldehydes into olefinic adducts in good to excellent yields. When constrained by structural features, the intermediate vic-diol can be isolated. Available data are consistent with a novel chromium Brook rearrangement.
- Baati, Rachid,Mioskowski, Charles,Barma, Deb,Kache, Rajashaker,Falck
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p. 2949 - 2951
(2007/10/03)
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- Stereoselective synthesis of (E)-hydroxystilbenoids by ruthenium-catalyzed cross-metathesis
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An efficient and highly stereoselective synthetic procedure is reported for the construction of symmetrical and unsymmetrical (E)-polymethoxystilbene and (E)-polyhydroxystilbene derivatives. The strategy rests on a cross-metathesis reaction catalyzed by stable, well-defined (alkylidene)ruthenium complexes, in particular the second-generation Grubbs catalyst [RuCl2(=CHPh)(SIMes) (PCy3)] [SIMes = 1,3-bis(2,4,6-trimethylphenyl)imidazolidin-2- ylidene]. The metathesis of unprotected phenolic styrenes is illustrated by the synthesis of the important phytoalexins (E)-3,4′,5-trihydroxystilbene (resveratrol) and (E)-3,3′,4,5′-tetrahydroxystilbene (piceatannol). Wiley-VCH Verlag GmbH & Co. KGaA, 2005.
- Ferre-Filmon, Karine,Delaude, Lionel,Demonceau, Albert,Noels, Alfred F.
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p. 3319 - 3325
(2007/10/03)
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- Low-valent titanium mediated synthesis of hydroxystilbenoids: Some new observations
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A series of phenolic stilbenoids possessing different numbers and positions of hydroxylation, partial methoxyl substituents and nature of olefinic moieties has been synthesized by McMurry coupling. It is found that the McMurry coupling of the phenolic aldehydes furnishes the dihydrostilbenes via an in situ hydrogenation, while the phenolic ketones give the stilbenes. Interestingly, the study also reveals that the low-valent titanium reagent (TiCl 3-Zn-THF) could selectively depyranylate phenolic -OTHP function without affecting alcoholic -OTHP group.
- Shadakshari,Rele,Nayak,Chattopadhyay
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p. 1934 - 1938
(2007/10/03)
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- Hydroxystilbene compounds for reducing/inhibiting protein glycation
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The hydroxystilbenes are well suited for reducing or inhibiting the glycation of certain substrates, for example the proteins of nails and/or hair, advantageously to preventatively and/or curatively combat glycation-related aging of the nails/hair.
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- Efficiency and structure-activity relationship of the antioxidant action of resveratrol and its analogs
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Resveratrol and its analogs, six other polyhydroxystilbenes, were synthesized and their antioxidative activities were evaluated in vitro by determination of the levels of malondialdehyde and hydrogen peroxide. Results clearly exhibited that resveratrol and its analogs had various potencies in inhibiting lipid peroxidation in rat brain, kidney, and liver homogenates and rat erythrocyte hemolysis. Several polyhydroxystilbenes were found to be more active than resveratrol in these models, and structure-activity relationship studies on polyhydroxystilbenes are described in this paper.
- Lu,Cai,Fang,Zhou,Liu,Wu, Longmin M.
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p. 474 - 478
(2007/10/03)
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- Electronic and magnetic metal-metal interactions in dinuclear oxomolybdenum(V) complexes across bis-phenolate bridging ligands with different spacers between the phenolate termini: Ligand-centred vs. metal-centred redox activity
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A series of dinuclear complexes has been prepared in which two {MoV(TpMe,Me)(O)Cl} fragments (abbreviated as Mo; TpMe,Me = tris(3,5-dimethylpyrazol-1-yl)hydroborate) are attached to either end of a bis-p-phenolate bridging ligand [(4,4′-OC6 H4)-X-(4,4′-C6H4O)]2-. The complexes are Mo2 (C=C)(X = CH=CH), Mo2(C=C)2 (X = CH=CH-CH=CH), Mo2(C=C)3 (X = CH=CH-CH=CH-CH=CH), Mo2(th) (X = 2,5-thiophenediyl), Mo2(th)2 (X = 2,5:2′,5′-bithiophenediyl), Mo2(th)3 (X = 2,5:2′,5′:2″,5″-terthiophenediyl), Mo2 (C≡C) (X = C≡C), Mo2(N=N) (X = N=N), Mo2(CO) [X = C(O)] and Mo2(C2ΦC2) [X = CH=CH(1,4-C6H4)CH=CH]. Electrochemical, UV/VIS/NIR spectroelectrochemical and magnetic measurements have been carried out in order to see how effectively the different spacer groups X mediate electronic and magnetic interactions between the two redox-active, paramagnetic, Mo centres. The electronic interactions were determined from the redox separation between the two successive one-electron oxidations which are formally Mo(VI)-Mo(V) couples; it was found that thienyl units in the bridging ligand are much more effective at maintaining electronic communication over long distances than p-phenylene or ethenyl spacers of comparable lengths. The azo (N=N) linkage afforded a much weaker electronic interaction than the ethenyl or ethynyl spacers. UV/VIS/NIR spectroelectrochemical studies showed that whereas the first oxidation is metal-centred to give Mo(VI)-Mo(V) species with characteristic intense phenolate→Mo(VI) LMCT transitions in the near-IR region, the spectra of the doubly oxidised complexes are characteristic of quinones: thus, the sequence of species formed on oxidation is [Mo(V)(μ-diolate)Mo(V)]0→[Mo(V)(μ-diolate)Mo(VI)] +→[Mo(V)(μ-quinone)Mo(V)]+2, with an internal charge redistribution associated with the second oxidation. Semi-empirical ZINDO calculations provide some support for this. Magnetic susceptibility measurements on Mo2(C=C), Mo2(th), Mo2(N=N) and Mo2(C≡C) show that all are weakly antiferromagnetically coupled, as expected on the basis of a spin-polarisation picture, with the order of strength of the magnetic interaction being the reverse of the order for electronic coupling, such that Mo2(th) affords the strongest electronic interaction but the weakest magnetic interaction.
- Bayly,Humphrey,De Chair,Paredes,Bell,Jeffery,McCleverty,Ward,Totti,Gatteschi,Courric,Steele,Screttas
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p. 1401 - 1414
(2007/10/03)
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- Synthesis and nematocidal activity of hydroxystilbenes
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Various (E)-hydroxystilbenes were synthesized from (E)/(Z) mixtures of methoxystilbenes through a new (Z)-(E) isomerization method followed by demethylation. The nematocidal activity appears when methoxystilbenes are demethylated to hydroxystilbenes. For this activity, a hydroxy group at the C-2 or C-3 position is necessary. Thus, 2-hydroxy-, 3-hydroxy-, 2,6-dihydroxy-, 3,4-dihydroxy-, 3,5-dihydroxy-, 2,2'-dihydroxy-, 3,3'-dihydroxy-, 3,4'dihydroxy-, 2-hydroxy-4-methoxy-, 5-hydroxy-2-methoxy-, 2-hydroxy-6-methoxy-, 6-allyloxy-2-hydroxy-, 3-hydroxy-5-methoxy-, and 5-allyloxy-3-hydroxystilbenes showed rather potent nematocidal activity. The activity of 5-allyloxy-3-hydroxystilbene was the strongest [minimal lethal concentration (MLC) = 30 μM]. The activities of the (E) and (Z) isomers were comparable. The activities were also retained, though they were weaker, in the dihydro derivatives, hydroxybibenzyls.
- Ali,Kondo,Tsuda
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p. 1130 - 1136
(2007/10/02)
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- Vat dye and sulfur dye compositions
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Specific vatting accelerators according to claims 1 and 2 are described. These can be added to a vat dye or sulfur dye composition, or to a dye bath or printing paste containing a vat dye or sulfur dye, by virtue of which an improvement of dye yield, particularly on cellulose materials, is obtained.
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