- Jietacins, azoxy antibiotics with potent nematocidal activity: Design, synthesis, and biological evaluation against parasitic nematodes
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Jietacins, an azoxy antibiotic class of chemicals, were isolated from the culture broth of Streptomyces sp. KP-197. They have a unique structural motif, including a vinyl azoxy group and a long acyclic aliphatic chain, which is usually branched but non-branched in the case of jietacin C. During a drug discovery program, we found that jietacins display potent anthelmintic activity against parasitic nematodes and that jietacin A has a moderate or low acute toxicity (LD50 > 300 mg/kg) and no mutagenic potential in a mini Ames screen. This suggests that jietacins have potential for drug discovery research. In order to create a novel anthelmintic agent, we performed design, synthesis, and biological evaluation of jietacin derivatives against parasitic nematodes. Of these derivatives, we found that a fully synthesized simplified derivative exhibited better anthelmintic activity against three parasitic nematodes than natural jietacins. In addition, it had a better efficacy in vivo through oral administration against a mouse nematode. This indicated that the azoxy motif could prove useful as a template for anthelmintic discovery, possibly creating a class of anthelmintic with novel skeletons, a potential new mode of action, and providing further insight for rational drug design.
- Sugawara, Akihiro,Kubo, Masahiko,Hirose, Tomoyasu,Yahagi, Kyoichi,Tsunoda, Noriaki,Noguchi, Yoshihiko,Nakashima, Takuji,Takahashi, Yoko,Welz, Claudia,Mueller, Dennis,Mertens, Christina,Koebberling, Johannes,ōmura, Satoshi,Sunazuka, Toshiaki
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Read Online
- Synthesis of novel porphyrin-based lipids and their antibacterial activity
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The purpose of this study was to investigate the antibacterial activity of newly developed cationic amphiphilic lipids having porphyrin as head group against two types of gram-positive bacteria and three types of gramnegative bacteria. The antibacterial activity of quantitatively prepared porphyrin-based amphiphilic lipids is evaluated by the disc-diffusion method against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Klebsiella pneumoniae and Proteus vulgaris. These results are compared with the standard antibacterial activity of chloramphenicol. Both lipids showed antibacterial behaviour against gram-positive and gram-negative bacteria. Springer Science+Business Media, LLC 2010.
- Velidandi, Amarnath,Gadidasu, Kranthi Kumar,Patri, V.Srilakshmi
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- Hanishenols A-B, novel linear or methyl-branched glycerol enol ethers of the axinellid sponge Acanthella carteri (= Acanthella aurantiaca) from the Hanish Islands, Southern Red Sea
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The axinellid sponge Acanthella carteri Dendy, 1889 (= Acanthella aurantiaca Keller, 1889) from the Hanish Islands, Yemen, on EtOH extraction followed by FC and HPLC purification gave the first example of branched glycerol enol ether, hanishenol B (3) alongside a major unbranched analogue, hanishenol A (1). Their structures were elucidated from NMR and MS spectra and through the ozonolysis product of 1, while the absolute configuration was assigned from exciton coupling with the dibenzoate derivative 2.
- Mancini, Ines,Guella, Graziano,Pietra, Francesco,Amade, Philippe
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Read Online
- Lysosomal delivery of a lipophilic gemcitabine prodrug using novel acid-sensitive micelles improved its antitumor activity
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Stimulus-sensitive micelles are attractive anticancer drug delivery systems. Herein, we reported a novel strategy to engineer acid-sensitive micelles using a amphiphilic material synthesized by directly conjugating the hydrophilic poly(ethylene glycol) (PEG) with a hydrophobic stearic acid derivative (C18) using an acid-sensitive hydrazone bond (PHC). An acid-insensitive PEG-amide-C18 (PAC) compound was also synthesized as a control. 4-(N)-Stearoyl gemcitabine (GemC18), a prodrug of the nucleoside analogue gemcitabine, was loaded into the micelles, and they were found to be significantly more cytotoxic to tumor cells than GemC18 solution, likely due to the lysosomal delivery of GemC18 by micelles. Moreover, GemC18 in the acid-sensitive PHC micelles was more cytotoxic than in the acid-insensitive PAC micelles, which may be attributed to the acid-sensitive release of GemC18 from the PHC micelles in lysosomes. In B16-F10 melanoma-bearing mice, GemC18-loaded PHC or PAC micelles showed stronger antitumor activity than GemC18 or gemcitabine solution, likely because of the prolonged circulation time and increased tumor accumulation of the GemC18 by the micelles. Importantly, the in vivo antitumor activity of GemC18-loaded PHC micelles was significantly stronger than that of the PAC micelles, demonstrating the potential of the novel acid-sensitive micelles as an anticancer drug delivery system.
- Zhu, Saijie,Lansakara-P., Dharmika S. P.,Li, Xinran,Cui, Zhengrong
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- Balancing the efficacy vs. the toxicity of promiscuous natural products: Paclitaxel-based acid-labile lipophilic prodrugs as promising chemotherapeutics
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TumorSelect is an anticancer technology that combines cytotoxics, nanotechnology, and knowledge of human physiology to develop innovative therapeutic interventions with minimal undesirable side effects commonly observed in conventional chemotherapy. Tumors have a voracious appetite for cholesterol which facilitates tumor growth and fuels their proliferation. We have transformed this need into a stealth delivery system to disguise and deliver anticancer drugs with the assistance of both the human body and the tumor cell. Several designer prodrugs are incorporated within pseudo-LDL nanoparticles, which carry them to tumor tissues, are taken up, internalized, transformed into active drugs, and inhibit cancer cell proliferation. Highly lipophilic prodrug conjugates of paclitaxel suitable for incorporation into the pseudo-LDL nanoparticles of the TumorSelect delivery vehicle formulation were designed, synthesized, and evaluated in the panel of 24-h NCI-60 human tumor cell line screening to demonstrate the power of such an innovative approach. Taxane prodrugs, viz., ART-207 was synthesized by tethering paclitaxel to lipid moiety with the aid of a racemic solketal as a linker in cost-effective, simple, and straightforward synthetic transformations. In addition to the typical 24-h NCI screening protocol, these compounds were assessed for growth inhibition or killing of ovarian cell lines for 48 and 72h-time intervals and identified the long-lasting effectiveness of these lipophilic prodrugs. All possible, enantiomerically pure isomers of ART-207 were also synthesized, and cytotoxicities were biosimilar to racemic ART-207, suggesting that enantiopurity of linker has a negligible effect on cell proliferation. To substantiate further, ART-207 was evaluated for its in vivo tumor reduction efficacy by studying the xenograft model of ovarian cancer grown in SCID mice. Reduced weight loss (a measure of toxicity) in the ART-207 group was observed, even though it was dosed at 2.5x the paclitaxel equivalent of Abraxane. As a result, our delineated approach is anticipated to improve patient quality of life, patient retention in treatment regimes, post-treatment rapid recovery, and overall patient compliance without compromising the efficacy of the cytotoxic promiscuous natural products.
- Chittiboyina, Amar G.,Claudio, Pier Paolo,Haider, Saqlain,McChesney, James D.,Penfornis, Patrice
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- Ortho -Substituted lipidated Brartemicin derivative shows promising Mincle-mediated adjuvant activity
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The macrophage inducible C-type lectin (Mincle) is a pathogen recognition receptor (PRR) that is a promising target for the development of Th1-polarising vaccine adjuvants. We recently reported on the synthesis and evaluation of lipidated Brartemicin analogues that showed Mincle agonist activity, with our lead agonist exhibiting potent Th1 adjuvant activity that was greater than that of trehalose dibehenate (TDB). Herein, we report on the efficient synthesis and subsequent biological evaluation of additional lipidated Brartemicin analogues that were designed to determine the structural requirements for optimal Mincle signalling. While all the Brartemicin analogues retained their ability to signal through Mincle and induce a functional response, the o-substituted and m,m-disubstituted derivatives (5a and 5d, respectively) induced a potent inflammatory response when using cells of both murine and human origin, with this response being the greatest observed thus far. As the inflammatory response elicited by 5a was slightly better than that induced by 5d, our findings point to o-substituted Brartemicin analogues as the preferred scaffold for further adjuvant development.
- Foster, Amy J.,Kodar, Kristel,Stocker, Bridget L.,Timmer, Mattie S. M.
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supporting information
p. 1095 - 1103
(2020/02/22)
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- A Simple and Effective Method for Catalytic Oxidation of Alcohols Using the Oxone/Bu4NHSO4 Oxidation System
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Abstract: A simple and efficient procedure is reported for the oxidation of alcohols tocarbonyl compounds with Oxone (potassium peroxymonosulfate) in the presence oftetrabutylammonium hydrogen sulfate as catalyst with excellent conversion andhigh selectivity using chloroform as solvent at room temperature. The efficiencyof several phase-transfer catalysts in the oxidation of benzyl alcohols andbenzydrol was studied. The proposed catalytic system was also evaluated in theoxidation of alcohols in water at room temperature.
- An, X. Q.,Kang, M.,Ma, H. C.,Yang, Y. X.,Yang, Z. W.,Zeng, W.
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p. 521 - 523
(2020/04/29)
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- Acridine Photocatalysis: Insights into the Mechanism and Development of a Dual-Catalytic Direct Decarboxylative Conjugate Addition
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Conjugate addition is one of the most synthetically useful carbon-carbon bond-forming reactions; however, reactive carbon nucleophiles are typically required to effect the addition. Radical conjugate addition provides an avenue for replacing reactive nucleophiles with convenient radical precursors. Carboxylic acids can serve as simple and stable radical precursors by way of decarboxylation, but activation to reactive esters is typically necessary to facilitate the challenging decarboxylation. Here, we report a direct, dual-catalytic decarboxylative radical conjugate addition of a wide range of carboxylic acids that does not require acid preactivation and is enabled by the visible light-driven acridine photocatalysis interfaced with an efficient copper catalytic cycle. Mechanistic and computational studies provide insights into the roles of the ligands and metal species in the dual-catalytic process and the photocatalytic activity of substituted acridines.
- Arman, Hadi D.,Dang, Hang T.,Haug, Graham C.,Larionov, Oleg V.,Nguyen, Viet D.,Nguyen, Vu T.,Vuong, Ngan T. H.
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p. 11448 - 11457
(2020/11/17)
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- Influence of Some Factors on the Progress of a New Reaction in the Chemistry of Organoaluminum Compounds
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Abstract: We earlier discovered a new reaction in the chemistry of organoaluminum compounds (OACs), specifically, the formation of O-isobutyl acetals on low-temperature (–70°C) treatment of seven-membered lactones with a double (or more) molar amount of diisobutylaluminum hydride (DIBAH) in methylene chloride. To assess the boundaries for the formation of isobutyl acetals depending on the ring size, we involved in the low-temperature hydride reduction six-, eight-, and thirteen-membered lactones. To determine how the scope of the new reaction depends on the nature of the organoaluminum reagent, we tested triisobutylaluminum (TIBA). To determine how the formation of isobutyl acetals on low-temperature (–70°C) reduction with excess DIBAH in CH2Cl2 depends on whether the starting ester is cyclic or acyclic and, if the former is the case, on the ring size in the ester, we used the acyclic methyl octadecanoate as the starting compound. It was found that the new reaction in the chemistry of AOC with DIBAH as the reducer is characteristic only of seven-membered lactones and atypical of acyclic methyl octadecanoate and ricinoleate (i.e. acids with the carbon chain length more than 6).
- Ishmuratov, G. Yu.,Vydrina, V. A.,Yakovleva, M. P.
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p. 1353 - 1358
(2020/10/02)
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- BRARTEMICIN ANALOGUES
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The invention relates to brartemicin analogues of Formula (IV) and their uses. These compounds are potent Mincle agonists and Th1-stimulating vaccine adjuvants.
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Page/Page column 34; 73
(2019/05/22)
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- Lipidic synthetic alkaloids as SK3 channel modulators. Synthesis and biological evaluation of 2-substituted tetrahydropyridine derivatives with potential anti-metastatic activity
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Small Conductance Calcium (Ca2+)-activated potassium (K+) channels (SKCa) are now proved to be involved in many cancer cell behaviors such as proliferation or migration. The SK3 channel isoform was particularly described in breast cancer where it can be associated with the Orai1 Ca2+ channel to form a complex that regulates the Ca2+ homeostasis during tumor development and acts as a potent mediator of bone metastases development in vivo. Until now, very few specific blockers of Orai1 and/or SK3 have been developed as potential anti-metastatic compounds. In this study, we illustrated the synthesis of new families of lipophilic pyridine and tetrahydropyridine derivatives designed as potential modulators of SK3 channel. The toxicity of the newly synthesized compounds and their migration effects were evaluated on the breast cancer cell line MDA-MB-435s. Two molecules (7a and 10c) demonstrated a significant decrease in the SK3 channel-dependent migration as well as the SK3/Orai1-related Ca2+ entry. Current measurements showed that these compounds are more likely SK3-selective. Taken all together these results suggest that such molecules could be considered as promising anti-metastatic drugs in breast cancer.
- Braire, Julien,Chant?me, Aurélie,Dubreuil, Didier,Félix, Romain,Jaffrès, Paul-Alain,Kouba, Sana,Lebreton, Jacques,Mathé-Allainmat, Monique,Pipelier, Muriel,Potier-Cartereau, Marie,Trebak, Mohamed,Vandier, Christophe,Zhang, Xuexin
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- Tandem IBX-Promoted Primary Alcohol Oxidation/Opening of Intermediate β,γ-Diolcarbonate Aldehydes to (E)-γ-Hydroxy-α,β-enals
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A tandem IBX-promoted oxidation of primary alcohol to aldehyde and opening of intermediate β,γ-diolcarbonate aldehyde to (E)-γ-hydroxy-α,β-enal has been developed. Remarkably, the carbonate opening delivered exclusively (E)-olefin and no over-oxidation of γ-hydroxy was observed. The method developed has been extended to complete the stereoselective total synthesis of both (S)- and (R)-coriolides and d-xylo- and d-arabino-C-20 guggultetrols.
- Kumari, Anupama,Gholap, Sachin P.,Fernandes, Rodney A.
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p. 2278 - 2290
(2019/06/17)
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- Chemoselective Hydrodeoxygenation of Carboxylic Acids to Hydrocarbons over Nitrogen-Doped Carbon-Alumina Hybrid Supported Iron Catalysts
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The establishment of catalyst systems for the chemoselective hydrodeoxygenation (HDO) of carboxylic acids to hydrocarbons, such as the HDO of long-chain fatty acids to alkanes, is important for biomass to biofuel conversion. As the most abundant and probably the cheapest transition metal on the earth, iron is a promising non-noble-metal alternative to precious metals for large-scale conversion of biomass. However, it usually suffers from unsatisfactory activity. In this work, a nitrogen-doped carbon-alumina hybrid supported iron (Fe-N-C@Al2O3) catalyst is established for chemoselective HDO of carboxylic acids to hydrocarbons. By using stearic acid HDO as the model reaction, n-octadecane and n-heptadecane are produced with yields of 91.9% and 6.0%, respectively. Triglycerides can also be converted into liquid alkanes with a total molar yield of >92%. In addition, the iron catalyst can chemoselectively catalyze the HDO of the carboxylic acid group in the presence of other functional groups such as an aromatic ring. This chemoselectivity has rarely been seen before because the aromatic ring is usually more easily hydrogenated in comparison to HDO of the carboxylic acid group. The characterization results showed that both the formation of a nitrogen-doped carbon-alumina hybrid and the iron loading are important for the Lewis basicity of these catalysts, in order to adsorb the acid substrates. The addition of melamine as the nitrogen precursor during pyrolysis eliminates undesired reactions between the iron precursor and alumina support to form an inactive hercynite phase, leading to the formation of an Fe3C active phase for the hydrogenation of -COOH to -CH2OH and the hybrid of N-C and alumina for the HDO of -CH2OH to -CH3.
- Li, Jiang,Zhang, Junjie,Wang, Shuai,Xu, Guangyue,Wang, Hao,Vlachos, Dionisios G.
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p. 1564 - 1577
(2019/02/03)
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- NOVEL SUGAR DERIVATIVE GELATORS
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A novel gelator including a sugar derivative; a gelator including a compound of Formula (1) or Formula (2): wherein R1 is a linear or branched alkyl group having a carbon atom number of 9 to 20, a cyclic alkyl group having a carbon atom number of 13 to 20, or a linear or branched alkenyl group having a carbon atom number of 9 to 20, R2 is a hydrogen atom, a linear or branched alkyl group having a carbon atom number of 1 to 10, or an aryl group optionally having a substituent, and R3 and R4 are hydroxy groups.
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Paragraph 0197; 0202; 0203
(2018/08/12)
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- Synthesis of Branched Trehalose Glycolipids and Their Mincle Agonist Activity
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The macrophage inducible C-type lectin (Mincle) is a pattern recognition receptor that recognizes trehalose dimycolate (TDM), and trehalose dibehenate (TDB) and related trehalose diesters, and thus represents a promising target for the development of vaccine adjuvants based on the trehalose glycolipid scaffold. To this end, we report on the synthesis of a series of long-chain α-branched, β-modified trehalose monoesters and diesters to explore how glycolipid structure affects signaling through Mincle. Key steps in our synthetic strategy include a Fráter-Seebach α-alkylation to install the C20 aliphatic lipid on a malic acid derivative, and the formation of a β,γ-epoxide as an intermediate from which modifications to the β-position of the lipid can be made. Biological evaluation of the derivatives using nuclear factor of activated T cells (NFAT)-green fluorescent protein (GFP) reporter cell lines expressing mMincle or hMincle revealed that the hMincle agonist activity of all diesters was superior to that of the current lead trehalose glycolipid adjuvant TDB, while the activity of several monoesters was similar to that of their diester counterparts for mMincle, but all showed reduced hMincle agonist activity. Taken together, diesters 2d-g are thus potent Mincle agonists and promising vaccine adjuvants.
- Bird, Jessie H.,Khan, Ashna A.,Nishimura, Naoya,Yamasaki, Sho,Timmer, Mattie S. M.,Stocker, Bridget L.
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p. 7593 - 7605
(2018/05/30)
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- Water soluble new bimetallic catalyst [CuZn(bz)3(bpy)2]PF6 in hydrogen peroxide mediated oxidation of alcohols to aldehydes/ketones and C-N functional groups
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A new heterobimetallic [CuZn(bz)3(bpy)2]PF6 has been synthesized from commercially available starting materials. Its structure has been established by molar conductance, magnetic moment, IR, electronic, ESR and X-ray crystallography. Its catalysis has been established in hydrogen peroxide mediated oxidation of alcohols to aldehydes and ketones and direct formation of oximes.
- Syiemlieh, Ibanphylla,Asthana, Mrityunjaya,Asthana, Sharad K.,Kurbah, Sunshine D.,Koch, Angira,Lal, Ram A.
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- Unexpected AChE inhibitory activity of (2E)α,β-unsaturated fatty acids
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A small library of (E) α,β-unsaturated fatty acids was prepared, and 20 different saturated and mono-unsaturated fatty acids differing in chain length were subjected to Ellman's assays to determine their ability to act as inhibitors for AChE or BChE. While the compounds were only very weak inhibitors of BChE, seven molecules were inhibitors of AChE holding IC50 = 4.3–12.8 M with three of them as significant inhibitors of this enzyme. The results have shown trans 2-mono-unsaturated fatty acids are better inhibitors for AChE than their saturated analogs. Furthermore, the screening results indicate that the chain length is crucial for obtaining an inhibitory efficacy. The best results were obtained for (2E) eicosenoic acid (14) showing inhibition constants Ki = 1.51 ± 0.09 M and Ki′ = 7.15 ± 0.55 M. All tested compounds were mixed-type inhibitors with a dominating competitive part. Molecular modelling calculations indicate a different binding mode of active/inactive compounds for the enzymes AChE and BChE.
- Loesche, Anne,Wiemann, Jana,Al Halabi, Zayan,Karasch, Julia,Sippl, Wolfgang,Csuk, René
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p. 3315 - 3319
(2018/09/17)
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- Dehydrogenation of primary aliphatic alcohols by Au/TiO2 photocatalysts
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Dehydrogenation reaction of primary aliphatic alcohols to aldehydes and molecular hydrogen was achieved under UV-vis light irradiation in the presence of gold-loaded titanium dioxide (Au/TiO2) photocatalysts.
- Shibata, Masaki,Nagata, Ryoko,Saito, Susumu,Naka, Hiroshi
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supporting information
p. 580 - 582
(2017/04/03)
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- Characterization of Carboxylic Acid Reductases as Enzymes in the Toolbox for Synthetic Chemistry
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Carboxylic acid reductase enzymes (CARs) meet the demand in synthetic chemistry for a green and regiospecific route to aldehydes from their respective carboxylic acids. However, relatively few of these enzymes have been characterized. A sequence alignment with members of the ANL (Acyl-CoA synthetase/ NRPS adenylation domain/Luciferase) superfamily of enzymes shed light on CAR functional dynamics. Four unstudied enzymes were selected by using a phylogenetic analysis of known and hypothetical CARs, and for the first time, a thorough biochemical characterization was performed. Kinetic analysis of these enzymes with various substrates shows that they have a broad but similar substrate specificity. Electron-rich acids are favored, which suggests that the first step in the proposed reaction mechanism, attack by the carboxylate on the α-phosphate of adenosine triphosphate (ATP), is the step that determines the substrate specificity and reaction kinetics. The effects of pH and temperature provide a clear operational window for the use of these CARs, whereas an investigation of product inhibition by NADP+, adenosine monophosphate, and pyrophosphate indicates that the binding of substrates at the adenylation domain is ordered with ATP binding first. This study consolidates CARs as important and exciting enzymes in the toolbox for sustainable chemistry and provides specifications for their use as a biocatalyst.
- Finnigan, William,Thomas, Adam,Cromar, Holly,Gough, Ben,Snajdrova, Radka,Adams, Joseph P.,Littlechild, Jennifer A.,Harmer, Nicholas J.
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p. 1005 - 1017
(2017/03/27)
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- De novo protecting-group-free total synthesis of (+)-muricadienin, (+)-ancepsenolide and (+)-3-hexadecyl-5-methylfuran-2(5 H)-one
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A de novo protecting-group-free total synthesis of (+)-muricadienin, (+)-ancepsenolide and (+)-3-hexadecyl-5-methylfuran-2(5H)-one has been achieved. Ring-closing-metathesis has been the key step in the synthesis. In (+)-muricadienin synthesis, a long chain alkyl group has been installed by an sp-sp3 Sonogashira type reaction followed by a cis-selective Lindlar reduction. The total synthesis is achieved in 7 steps and in excellent 43.5% overall yield. Similarly, (+)-ancepsenolide and (+)-3-hexadecyl-5-methylfuran-2(5H)-one synthesis is completed in 5 steps each and in 48 and 68% overall yields, respectively.
- Kunkalkar, Rupesh A.,Laha, Debasish,Fernandes, Rodney A.
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p. 9072 - 9079
(2016/10/07)
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- Design and synthesis of protein kinase C epsilon selective diacylglycerol lactones (DAG-lactones)
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DAG-lactones afford a synthetically accessible, high affinity platform for probing structure activity relationships at the C1 regulatory domain of protein kinase C (PKC). Given the central role of PKC isoforms in cellular signaling, along with their differential biological activities, a critical objective is the design of isoform selective ligands. Here, we report the synthesis of a series of DAG-lactones varying in their side chains, with a particular focus on linoleic acid derivatives. We evaluated their selectivity for PKC epsilon versus PKC alpha both under standard lipid conditions (100% phosphatidylserine, PS) as well as in the presence of a nuclear membrane mimetic lipid mixture (NML). We find that selectivity for PKC epsilon versus PKC alpha tended to be enhanced in the presence of the nuclear membrane mimetic lipid mixture and, for our lead compound, report a selectivity of 32-fold.
- Ann, Jihyae,Yoon, Suyoung,Baek, Jisoo,Kim, Da Hye,Lewin, Nancy E.,Hill, Colin S.,Blumberg, Peter M.,Lee, Jeewoo
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p. 332 - 341
(2015/05/04)
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- Pheromone Bouquet of the Dried Bean Beetle, Acanthoscelides obtectus (Col.: Chrysomelidae), Now Complete
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Male-specific volatile components, released by the dried bean beetle, Acanthoscelides obtectus, were identified as methyl (E,R)-2,4,5-tetradecatrienoate, methyl (2E,4Z,7Z)-2,4,7-decatrienoate, methyl (2E,4Z)-2,4-decadienoate, octadecanal and the sesquiterpenes (3Z,6E)- and (3E,6E)-α-farnesene. In olfactometer bioassays, pure methyl (E,R)-2,4,5-tetradecatrienoate was only weakly attractive to unmated females. However, a blend of the six identified compounds released in physiologically relevant ratios and doses proved to be as active as headspace odours collected from live males.
- Vuts, J?zsef,Francke, Wittko,Mori, Kenji,Zarbin, Paulo H. G.,Hooper, Antony M.,Millar, Jocelyn G.,Pickett, John A.,T?th, Mikl?s,Chamberlain, Keith,Caulfield, John C.,Woodcock, Christine M.,Tr?ger, Armin G.,Csonka, éva Bálintné,Birkett, Michael A.
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p. 4843 - 4846
(2015/08/03)
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- Selective hydrogenation of fatty acids to alcohols over highly dispersed ReOx/TiO2 catalyst the paper is dedicated to the living memory of Dr. Haldor Topsoe.
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Production of fatty alcohols through selective hydrogenation of fatty acids was studied over a 4% ReOx/TiO2 catalyst. Stearic acid was hydrogenated to octadecanol at temperatures and pressures between 180-200°C and 2-4 MPa, with selectivity reaching 93%. A high yield of octadecanol was attributed to a strong adsorption of the acid compared to alcohol on the catalyst, which inhibits further alcohol transformation to alkanes. Low amounts (7%) of alkanes (mainly octadecane) were formed during the conversion of stearic acid. However, it was found that the catalyst could be tuned for the production of alkanes. The reaction intermediates were octadecanal and stearyl stearate. Based on the reaction products analysis and catalyst characterization, a reaction mechanism and possible pathways were proposed.
- Rozmyslowicz, Bartosz,Kirilin, Alexey,Aho, Atte,Manyar, Haresh,Hardacre, Christopher,W?rn?, Johan,Salmi, Tapio,Murzin, Dmitry Yu.
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p. 197 - 207
(2015/08/04)
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- Impact of the oxygen defects and the hydrogen concentration on the surface of tetragonal and monoclinic ZrO2 on the reduction rates of stearic acid on Ni/ZrO2
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The role of the specific physicochemical properties of ZrO2 phases on Ni/ZrO2 has been explored with respect to the reduction of stearic acid. Conversion on pure m-ZrO2 is 1.3 times more active than on t-ZrO2, whereas Ni/m-ZrO2 is three times more active than Ni/t-ZrO2. Although the hydrodeoxygenation of stearic acid can be catalyzed solely by Ni, the synergistic interaction between Ni and the ZrO2 support causes the variations in the reaction rates. Adsorption of the carboxylic acid group on an oxygen vacancy of ZrO2 and the abstraction of the a-hydrogen atom with the elimination of the oxygen atom to produce a ketene is the key to enhance the overall rate. The hydrogenated intermediate 1-octadecanol is in turn decarbonylated to heptadecane with identical rates on all catalysts. Decarbonylation of 1-octadecanol is concluded to be limited by the competitive adsorption of reactants and intermediate. The substantially higher adsorption of propionic acid demonstrated by IR spectroscopy and the higher reactivity to O2 exchange reactions with the more active catalyst indicate that the higher concentration of active oxygen defects on m-ZrO2 compared to t-ZrO2 causes the higher activity of Ni/m-ZrO2.
- Foraita, Sebastian,Fulton, John L.,Chase, Zizwe A.,Vjunov, Aleksei,Xu, Pinghong,Barth, Eszter,Camaioni, Donald M.,Zhao, Chen,Lercher, Johannes A.
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p. 2423 - 2434
(2015/02/05)
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- TEMPO-mediated oxidation of primary alcohols to aldehydes under visible light and air
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A homogeneous visible light photoredox TEMPO-mediated selective oxidation of primary alcohols to the corresponding carbonyl compounds was developed using molecular oxygen from air as the terminal oxidant. Ru(bpy)3(PF 6)2 (bpy: bipyridyl) and Ir(dtb-bpy)(ppy) 2(PF6) (dtb-bpy: 4,4′-di-tert-butyl-2,2′- bipyridyl; ppy: 2-phenylpyridine) were used as the sensitizers. A homogeneous visible light photoredox TEMPO-mediated selective oxidation of primary alcohols to the corresponding carbonyl compounds was developed. Molecular oxygen from air was the terminal oxidant. Copyright
- Liu, Dongwang,Zhou, Hongxia,Gu, Xiangyong,Shen, Xiaoqin,Li, Pixu
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supporting information
p. 117 - 122
(2014/03/21)
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- Hypervalent iodine/TEMPO-mediated oxidation in flow systems: A fast and efficient protocol for alcohol oxidation
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Hypervalent iodine(III)/TEMPO-mediated oxidation of various aliphatic, aromatic and allylic alcohols to their corresponding carbonyl compounds was successfully achieved by using microreactor technology. This method can be used as an alternative for the oxidation of various alcohols achieving excellent yields and selectivities in significantly shortened reaction times.
- Ambreen, Nida,Kumar, Ravi,Wirth, Thomas
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p. 1437 - 1442
(2013/08/23)
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- A divergent approach to the synthesis of simplexides and congeners via a late-stage olefin cross-metathesis reaction
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Simplexides constitute a unique group of immunosuppressive glycolipids that demonstrate antiproliferative activities against activated T-cell lymphocytes via a unique non-cytotoxic inhibition. To investigate the structure-activity relationship of the varied long-chain secondary alcohols on simplexides, we developed an efficient and divergent route to the synthesis of simplexides and congeners, taking advantage of a late-stage olefin cross-metathesis reaction.
- Li, Jiakun,Li, Wei,Yu, Biao
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supporting information
p. 4971 - 4974
(2013/08/23)
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- The ORF slr0091 of Synechocystis sp. PCC6803 encodes a high-light induced aldehyde dehydrogenase converting apocarotenals and alkanals
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Oxidative cleavage of carotenoids and peroxidation of lipids lead to apocarotenals and aliphatic aldehydes called alkanals, which react with vitally important compounds, promoting cytotoxicity. Although many enzymes have been reported to deactivate alkanals by converting them into fatty acids, little is known about the mechanisms used to detoxify apocarotenals or the enzymes acting on them. Cyanobacteria and other photosynthetic organisms must cope with both classes of aldehydes. Here we report that the Synechocystis enzyme SynAlh1, encoded by the ORF slr0091, is an aldehyde dehydrogenase that mediates oxidation of both apocarotenals and alkanals into the corresponding acids. Using a crude lysate of SynAlh1-expressing Escherichia coli cells, we show that SynAlh1 converts a wide range of apocarotenals and alkanals, with a preference for apocarotenals with defined chain lengths. As suggested by in vitro incubations and using engineered retinal-forming E. coli cells, we found that retinal is not a substrate for SynAlh1, making involvement in Synechocystis retinoid metabolism unlikely. The transcript level of SynAlh1 is induced by high light and cold treatment, indicating a role in the stress response, and the corresponding gene is a constituent of a stress-related operon. The assumptions regarding the function of SynAlh are further supported by the surprisingly high homology to human and plant aldehyde dehydrogenase that have been assigned to aldehyde detoxification. SynAlh1 is the first aldehyde dehydrogenase that has been shown to form both apocarotenoic and fatty acids. This dual function suggests that its eukaryotic homologs may also be involved in apocarotenal metabolism, a function that has not been considered so far. Aldehyde dehydrogenases play an important role in detoxification of reactive aldehydes. Here, we report on a cyanbacterial enzyme capable in converting two classes of lipid-derived aldehydes, apocaotenals and alkanals. The corresponding gene is a constituent of a stress-related operon, and homology to eukaryotic enzymes points to a yet not considered possibility of their being involved in scavenging of apocarotenals.
- Trautmann, Danika,Beyer, Peter,Al-Babili, Salim
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p. 3685 - 3696
(2013/08/23)
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- The synthesis of long-chain α-alkyl-β-hydroxy esters using allylic halides in a Frater-Seebach alkylation
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The Frater-Seebach alkylation is a highly efficient means to diastereoselectively introduce α-substituents to chiral β-hydroxy esters, however, the yields of reactions in which longer chain alkyl halides are used can be disappointing. To provide a more robust protocol for the alkylation of β-hydroxy esters, we prepared a variety of long-chain allylic iodides with the view that the greater reactivity of the allylic system would lead to enhanced efficiency. Indeed, for all substrates studied, the yield of the α-alkylation was greatly improved for the unsaturated allylic halides compared to their analogous saturated counterparts. Our methodology thus provides an improved means by which to access a variety of important lipophilic compounds such as mycolic acids, which are found on the cell wall of M. tuberculosis. An improved methodology for the introduction of α-substituents to chiral β-hydroxy esters using Frater-Seebach methodology is presented. Long-chain allylic iodides resulted in better yields for the α-alkylation compared to their saturated counterparts. This methodology provides an improved means by which to access a variety of important lipophilic compounds such as mycolic acids. Copyright
- Khan, Ashna A.,Chee, Stephanie H.,Stocker, Bridget L.,Timmer, Mattie S. M.
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supporting information; experimental part
p. 995 - 1002
(2012/03/27)
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- Permeable composite membrane as a catalytically active contactor for hydrogenation reactions
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The efficiency of using of the permeable composite membrane (PCM) is demonstrated in the 3-phase reaction of liquid substrate with gaseous hydrogen on solid catalyst (PCM acts as a catalytically active contactor) - hydrogenation of fatty acid triglyceride. PCM provides a good combination of the opposite requirements of mild internal diffusion restrictions, low hydraulic resistance, high thermal conductivity, well-developed gas-liquid interface and high catalyst loading in the reactor volume, and thus assures the control of the course of the catalytic reaction.
- Minyukova, T. P.,Shtertser, N. V.,Khassin, A. A.,Yurieva, T. M.
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p. 107 - 110,4
(2020/08/20)
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- Synthesis and in vitro evaluation of analogues of avocado-produced toxin (+)-(R)-persin in human breast cancer cells
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A structure-activity study of several new synthetic analogues of the avocado-produced toxin persin has been conducted, with compounds being evaluated for their cytostatic and pro-apoptotic effects in human breast cancer cells. A 4-pyridinyl derivative demonstrated activity comparable to that of the natural product, suggesting future directions for exploration of structure-activity relationships.
- Brooke, Darby G.,Shelley, Elizabeth J.,Roberts, Caroline G.,Denny, William A.,Sutherland, Robert L.,Butt, Alison J.
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scheme or table
p. 7033 - 7043
(2012/01/06)
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- Synthesis and preferred conformations of all regio- and diastereoisomeric methyl 2,3-fluorohydroxyalkanoates
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Selective syntheses of enantiopure regio- and diastereomeric methyl 2,3-fluoro-hydroxyalkanoates via four different routes employing two types of fluorination reagents are reported. The anti- and syn-3-fluoro-2- hydroxyalkanoates 1 and 3 were prepared by treating the corresponding epoxides with Olah's reagent (Py·9HF). Cyclic sulfates prepared from the enantiomeric diols were ring-opened with TBAF to give the anti- and syn-2-fluoro-3-hydroxyalkanoates 2 and 4. Thestereochemical analysis was performed mainly by NMR spectroscopy. Applying DFT/B3LYP and SCS-MP2 quantum chemical methods, the coupling constants and relative energies of conformers were calculated. Solvent effects were considered using the COSMO continuum model. Regio- and stereoselective ring opening of enantio-pure epoxides or cyclic sulfates with pyridine·9HF or TBAF delivers anti- or syn-configurated 3-fluoro-2-hydroxy- or 2-fluoro-3-hydroxyalkanoates, respectively. The relative energies of conformers were calculated by quantum chemical methods. Those of 3-fluoro-2-hydroxy isomers are influenced by intramolecular O-H·O=C hydrogen bonds, while the regioisomers show close O-H·F-C contacts. Copyright
- Husstedt, Wibke S.,Wiehle, Susanne,Stillig, Christian,Bergander, Klaus,Grimme, Stefan,Haufe, Guenter
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experimental part
p. 355 - 363
(2011/02/28)
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- Comprehensive screening of octopus amphiphiles as DNA activators in lipid bilayers: Implications on transport, sensing and cellular uptake
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Dynamic octopus amphiphiles contain one charged "head," here a guanidinium cation, together several hydrophobic "tails" (or "tentacles") that can be attached and exchanged in situ by reversible hydrazone formation. Quite surprisingly, their ability to activate DNA as transporters in lipid bilayer membranes was found to increase with the number of tails (up to four) as well as with their length (up to eight carbons). Both encouraged and puzzled by these results, we decided that a comprehensive screening of octopus amphiphiles with regard to number (from one to six) and length (from three to eighteen carbons) of their tails would be appropriate at this point. For this purpose, we here report the synthesis of cationic hexahydrazide peptide dendrons together with that of aldehydes with long, saturated, unsaturated and branched hydrophobic tails. Comprehensive screening of the completed collection of tails and heads reveals that the ability of octopus amphiphiles to activate DNA transporters shifts with increasing number of tails to decreasing length of the tails. Moreover, cis-alkenyl and branched alkyl tails are more active than their linear analogs, branched aromatic tails are best. These overall very meaningful trends for octopus amphiphiles will be of importance for sensing applications and fragrant cellular uptake.
- Montenegro, Javier,Fin, Andrea,Matile, Stefan
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supporting information; experimental part
p. 2641 - 2647
(2011/05/15)
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- A novel synthetic method for the preparation of aliphatic aldehydes from the corresponding carboxylic acids
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A novel synthetic method for the preparation of aliphatic aldehydes from the corresponding carboxylic acids via 1,3-dimethylbenzimidazolium salts is provided. 1,3-Dimethylbenzimidazolium salts were rapidly reduced with sodium/ethanol and then hydrolyzed with hydrochloric acid to obtain aliphatic aldehydes, in which the 1,3-dimethylbenzimidazolium salts can be readily achieved from the corresponding carboxylic acids. The mechanism for the reductive reaction of 1,3-dimethylbenzimidazolium salts with sodium/ethanol was discussed.
- Guo, Yuan,Lu, Zhenhuan,Yao, Libo,Shi, Zhen
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experimental part
p. 489 - 492
(2012/01/05)
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- Neuroprotective effects of N-alkyl-1,2,4-oxadiazolidine-3,5-diones and their corresponding synthetic intermediates N-alkylhydroxylamines and N-1-alkyl-3-carbonyl-1-hydroxyureas against in vitro cerebral ischemia
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Herein we report the synthesis and neuroprotective effects of new N-alkyl-1,2,4-oxadiazolidine-3,5-diones and their corresponding synthetic intermediates, N-alkylhydroxylamines and N-1-alkyl-3-carbonyl-1-hydroxyureas, in an in vitro model of ischemia. We found five analogues that protect HT22 cells from death in the concentration range of 1-5 μm. Because members of the MAP kinase family are known to be key players in nerve cell survival and death, we characterized the role of these kinases in the neuroprotective mechanisms of the newly synthesized analogues. The results indicate that these compounds provide neuroprotection through distinct mechanisms of action.
- Biraboneye, Alain Cesar,Madonna, Sebastien,Maher, Pamela,Kraus, Jean-Louis
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experimental part
p. 79 - 85
(2010/11/02)
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- A green method for the self-aldol condensation of aldehydes using lysine
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A self-condensation of aldehydes has been conveniently accomplished by the catalytic action of lysine in water or a solvent-free system under specific emulsion conditions to give α-branched α,β-unsaturated aldehydes in good yields.
- Watanabe, Yutaka,Sawada, Kazue,Hayashi, Minoru
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body text
p. 384 - 386
(2010/08/04)
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- Transition-metal-catalyzed immobilization of organic functional groups onto solid supports through vinylsilane coupling reactions
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A novel and efficient grafting method for covalent bonding of functional organic molecules to silica or glass surfaces has been developed. The protocol employs transition-metal-catalyzed reactions of vinylsilanes with surface hydroxyl groups. Dimethyldivinylsilane can be used in this procedure as a linker in which one vinyl group is used for direct C-C bond formation with a functional organic molecule and the other is employed to immobilize the alkylsilyl group onto the hydroxyl surface of the solid support.
- Park, Jung-Woo,Jun, Chul-Ho
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supporting information; experimental part
p. 7268 - 7269
(2010/08/05)
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- Synthesis and evaluation of sphingolipid analogues modification of the hydroxy group at C(1) of 7-oxasphingosine, and of the hydroxy group at C(1) and the amide group of 7-oxaceramides
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The analogues 7-9 of 7-oxaceramide and 7-oxasphingosine were synthesized from the known azidosphingosine 21. The 1,4-disubstituted 1,2,3-triazole analogues 10-16 of ceramides were synthesized by the click reaction of the known azide 24. None of the analogues 7-15 was active as inhibitor of SPHK type 1 and of acid sphingomyelinase, whereas 16 is a weak inhibitor of SPHK1. Triazoles 10, 11, and 15 did not inhibit ceramide phosphorylation by CerK, and none of 7, 8, and 10-15 activated invariant natural killer T (iNKT) cell clones when presented by human CD1d-transfected antigen-presenting cells (APC) or by plate-bound human CD1d [55]. Triazoles 14 and 15 prevent binding of α-galactosylceramide (α-GalCer) to plate-bound human CD1d and subsequent T-cell response to α-GalCer. Only 15 reduced activation by α-GalCer significantly and independently of the cytokine measured.
- Mathew, Thresen,Billich, Andreas,Cavallari, Marco,Bornancin, Frederic,Nussbaumer, Peter,De Libero, Gennaro,Vasella, Andrea
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experimental part
p. 705 - 724
(2010/04/23)
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- Synthesis and C-alkylation of hindered aldehyde enamines
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A new reactivity mode of hindered lithium amides with terminal epoxides is described whereby aldehyde enamines are produced via a previously unrecognized reaction pathway. Some of these aldehyde enamines display unprecedented C-alkylation reactivity toward unactivated primary and secondary alkyl halides. For comparison, the reactivity of aldehyde enamines synthesized via a traditional condensation method was examined. C-rather than N-alkylation was the dominant reaction pathway found with a range of electrophiles, making this route to α-alkylated aldehydes more synthetically useful than previously reported.
- Hodgson, David M.,Bray, Christopher D.,Kindon, Nicholas D.,Reynolds, Nigel J.,Coote, Steven J.,Um, Joann M.,Houk
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body text
p. 1019 - 1028
(2009/07/04)
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- Sulfoglycolipid antigens, their process of preparation, and their use against tuberculosis
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The present invention relates to compounds of the following general formula: their process of preparation and their use in the treatment or the prophylaxis of tuberculosis.
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Page/Page column 18
(2008/12/07)
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- An efficient conversion of carboxylic acids to one-carbon degraded aldehydes via 2-hydroperoxy acids
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After the formation of dianions of a carboxylic acid with lithium diisopropylamide, oxygen was bubbled into the solution to produce 2-hydroperoxy acid. Then the reaction mixture was acidified with a 2N HCl solution and subsequently elevated to 50°C to afford the aldehyde with the loss of one carbon atom. Even saturated (C10-C20) and unsaturated (C18:1) carboxylic acids were converted into the odd aldehydes (C9-C19, C17:1) in high yields. This conversion was found to be an efficient method for the preparation of carboxylic acids (Cn) to one-carbon degraded aldehydes (Cn-1) via 2-hydroperoxy acids.
- Akakabe, Yoshihiko,Nyuugaku, Takeshi
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p. 1370 - 1371
(2008/02/07)
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- Isolation, structure elucidation, total synthesis, and evaluation of new natural and synthetic ceramides on human SK-MEL-1 melanoma cells
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Two new long-chain ceramides, trametenamides A (1) and B (2), were isolated from the methanolic extract of the fruiting body of the fungus Trametes menziesii. The structures were elucidated by spectroscopic analyses and chemical transformations, and the absolute stereochemistry of trametenamide B (2) was determined by stereoselective total synthesis of four possible diastereomers. The acetyl derivative of the natural ceramide (1a) and synthetic ceramides (24-27) showed cytotoxicity on the human melanoma cell line SK-MEL-1, which was caused by induction of apoptosis as determined by DNA fragmentation, poly-(ADP-ribose) polymerase cleavage, and procaspase-9 and -8 processing.
- León, Francisco,Brouard, Ignacio,Rivera, Augusto,Torres, Fernando,Rubio, Sara,Quintana, José,Estévez, Francisco,Bermejo, Jaime
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p. 5830 - 5839
(2007/10/03)
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- Synthesis of a novel class of fatty acids-derived isoquinolines
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Two series of novel tetrahydroisoquinoline derivatives bearing at C-1 position a carbon chain derived from fatty acids were prepared employing two complementary synthetic methodologies. The Pictet-Spengler condensation was performed on myristyl, palmityl, stearyl and oleyl aldehydes, whereas the Bischler-Napieralski cyclization used pelargonic, stearic, linolenic and arachidonic acids. The ability to apply both methods allows further labeling of the final 1-substituted-1,2,3,4-tetrahydroisoquinolines for biological studies.
- Matuszewska, Iwona,Leniewski, Andrzej,Roszkowski, Piotr,Czarnocki, Zbigniew
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p. 131 - 145
(2007/10/03)
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- Development and comparison of the substrate scope of Pd-catalysts for the aerobic oxidation of alcohols
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(Chemical Equation Presented) Three catalysts for aerobic oxidation of alcohols are discussed and the effectiveness of each is evaluated for allylic, benzylic, aliphatic, and functionalized alcohols. Additionally, chiral nonracemic substrates as well as chemoselective and diastereoselective oxidations are investigated. In this study, the most convenient system for the Pd-catalyzed aerobic oxidation of alcohols is Pd(OAc)2 in combination with triethylamine. This system functions effectively for the majority of alcohols tested and uses mild conditions (3 to 5 mol % of catalyst, room temperature). Pd(IiPr)(OAc)2(H2O) (1) also successfully oxidizes the majority of alcohols evaluated. This system has the advantage of significantly lowering catalyst loadings but requires higher temperatures (0.1 to 1 mol % of catalyst, 60°C). A new catalyst is also disclosed, Pd(IiPr)(OPiv)2 (2). This catalyst operates under very mild conditions (1 mol %, room temperature, and air as the O2 source) but with a more limited substrate scope.
- Schultz, Mitchell J.,Hamilton, Steven S.,Jensen, David R.,Sigman, Matthew S.
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p. 3343 - 3352
(2007/10/03)
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- Semivolatile and volatile compounds in combustion of polyethylene
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The evolution of semivolatile and volatile compounds in the combustion of polyethylene (PE) was studied at different operating conditions in a horizontal quartz reactor. Four combustion runs at 500 and 850°C with two different sample mass/air flow ratios and two pyrolytic runs at the same temperatures were carried out. Thermal behavior of different compounds was analyzed and the data obtained were compared with those of literature. It was observed that α,ω-olefins, α-olefins and n-paraffins were formed from the pyrolytic decomposition at low temperatures. On the other hand, oxygenated compounds such as aldehydes were also formed in the presence of oxygen. High yields were obtained of carbon oxides and light hydrocarbons, too. At high temperatures, the formation of polycyclic aromatic hydrocarbons (PAHs) took place. These compounds are harmful and their presence in the combustion processes is related with the evolution of pyrolytic puffs inside the combustion chamber with a poor mixture of semivolatile compounds evolved with oxygen. Altogether, the yields of more than 200 compounds were determined. The collection of the semivolatile compounds was carried out with XAD-2 adsorbent and were analyzed by GC-MS, whereas volatile compounds and gases were collected in a Tedlar bag and analyzed by GC with thermal conductivity and flame ionization detectors.
- Font, Rafael,Aracil, Ignacio,Fullana, Andrés,Conesa, Juan A.
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p. 615 - 627
(2007/10/03)
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- Cationic lipids with serine backbone
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The present invention provides cationic lipids with serine backbone, a composition for transferring biologically active molecules into cells and/or tissues comprising said cationic lipids, a process for the manufacture of said lipids, the use of said lipids as constituent of a transfection agent and a method for transferring biologically active molecules into cells and/or into tissues or for gene therapy.
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- Synthesis of modified Weinreb amides: N-tert-butoxy-N-methylamides as effective acylating agents
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An efficient preparation of N-methyl-O-tert-butylhydroxylamine hydrochloride has been settled, which allowed the synthesis of modified Weinreb amides. Nucleophilic addition of organolithium and Grignard reagents on these N-tert-butoxy-N-methylamides afforded efficiently the corresponding ketones and reduction with DIBAL furnished the corresponding aldehydes in good yields up to 97%.
- Labeeuw, Olivier,Phansavath, Phannarath,Genêt, Jean-Pierre
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p. 7107 - 7110
(2007/10/03)
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- Anti-cancer nitro- and thia-fatty acids
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The present invention relates to pharmaceutical compositions comprising, as an anti-cancer agent: (a) one or more compounds having the formula NO2-A-B, wherein A is a saturated or unsaturated hydrocarbon chain of 14-26 double bonds, and B is (CH2)m(COOH)n in which n is a integer from 0 to 2 and m is an integer from 0 to 2; or a derivative thereof in which the hydrocarbon chain has one or more than one substitution selected from the group consisting of hydroxy, hydroperoxy, epoxy and peroxy; (b) one or more compounds selected from polyunsaturated fatty acids (PUFA's) having a 16 to 26 carbon atom chain and 3 to 16 double bonds, and wherein the PUFA is covalently coupled at the carboxylic acid group to an amino acid selected from glycine and aspartic acid; (c) one or more compounds selected from unsaturated fatty acids having an 18 to 25 carbon atom chain and 1 to 6 double bonds and wherein the fatty acid has one or two beta-oxa, gamma-oxa, beta-thia, gamma-thia substitutions: or (d) one or more compounds having formula (I) wherein A' is a saturated or unsaturated hydrocarbon chain of 9-26 carbon atoms, X is oxygen or is absent and B' is (CH2)J(COOH)k in which j is an integer from 1 to 3 and K is 0 or 1; or a derivative thereof in which the hydrocarbon chain has one or more than one substitution selected from the group consisting of hydroxy, hydroperoxy, epoxy and peroxy; and a pharmaceutically acceptable carrier or diluent.
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- From T-antigen to plasmalogen-derived aldehydes: The identification of a marker of colorectal cancer in human rectal mucous
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Recently, a simple noninvasive screening test for colorectal cancer was proposed, based on a hypothesis involving galactose-containing carbohydrate moieties such as the Thomsen-Friedenreich antigen. According to the hypothesis, such carbohydrate moieties, present in the human rectal mucous of patients with colorectal cancer, can be specifically oxidized with galactose oxidase to form substances that, upon reaction with Schiff reagent, yield purple (magenta) coloured compounds. While evaluating this proposed test, we discovered that the colour formation is not due to the proposed reaction between oxidized galactose moieties present in rectal mucous and Schiff reagent. We found instead that the mucous from colorectal cancer patients contains compounds that form purple (magenta) adducts with the Schiff reagent directly, i.e., they do not require oxidation by galactose oxidase. We have identified these compounds as long-chain aliphatic aldehydes, mainly palmitic aldehyde C15H31CH=O and stearic aldehyde C17H35CH=O. We have further found that the aldehydes originate from plasmalogens present in the phospholipid fraction of the mucous obtained from colorectal cancer patients. The aldehydes, present in plasmalogens as enol ethers, are released by the acidity of the Schiff reagent and in turn react with the Schiff reagent to form the coloured adducts. Correct identification of these markers could lead to the development of a more accurate colorectal cancer screening tool and to a deeper understanding of colorectal carcinogenesis.
- Krepinsky, Jiri J.,Kandel, Gabor P.,Yeung, Ka Sing,Chociej, Jacek,Chen, Min,Cohen, Gideon,Douglas, Stephen P.,Furrer, Rudolf,Kukreti, Vishal,Lupescu, Niculina,Richens, Enoka,Tanner, Keith L.
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p. 109 - 117
(2007/10/03)
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- Anchor dependency for non-glycerol based cationic lipofectins: Mixed bag of regular and anomalous transfection profiles
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Although detailed structure-activity, physicochemical and biophysical investigations in probing the anchor influence in liposomal gene delivery have been reported for glycerol-based transfection lipids, the corresponding investigation for non-glycerol based simple monocationic transfection lipids have not yet been undertaken. Towards this end, herein, we delineate our structure-activity and physicochemical approach in deciphering the anchor dependency in liposomal gene delivery using fifteen new structural analogues (lipids 1-15) of recently reported non-glycerol based monocationic transfection lipids. The C14 analogues in both series 1 (lipids 1-6) and series 2 (lipids 7-15) showed maximum efficiency in transfecting COS-1 and CHO cells. However, the C12 analogue of the ether series (lipid 3) exhibited a seemingly anomalous behavior compared with its transfection efficient C10 and C14 analogues (lipids 2 and 4) in being completely inefficient to transfect both COS-1 and CHO cells. The present structure-activity investigation also convincingly demonstrates that enhancement of transfection efficiencies through incorporation of membrane re-organizing unsaturation elements in the hydrophobic anchor of cationic lipids is not universal but cell dependent. The strength of the interaction of lipids 1-15 with DNA was assessed by their ability to exclude ethidium bromide bound to the DNA. Cationic lipids with long hydrophobic tails were found, in general, to be efficient in excluding EtBr from DNA. Gel to liquid crystalline transition temperatures of the lipids was measured by fluorescence anisotropy measurement technique. In general (lipid 2 being an exception), transfection efficient lipids were found to have their mid transition temperatures at or below physiological temperatures (37°C).
- Singh, Rajkumar Sunil,Mukherjee, Koushik,Banerjee, Rajkumar,Chaudhuri, Arabinda,Hait, Samik Kumar,Moulik, Satya Priya,Ramadas, Yerramsetti,Vijayalakshmi, Amash,Rao, Nalam Madhusudhana
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p. 900 - 909
(2007/10/03)
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- Pd(II)-hydrotalcite-catalyzed oxidation of alcohols to aldehydes and ketones using atmospheric pressure of air
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A heterogenized Pd catalyst, Pd(II)-hydrotalcite (palladium(II) acetate-pyridine supported by hydrotalcite) catalyzes the aerobic oxidation in toluene of a variety of primary and secondary alcohols into the corresponding aldehydes and ketones in high yields using atmospheric pressure of air as a sole oxidant under mild conditions. This catalyst is also effective for the oxidation of allylic alcohols, especially such as geraniol and nerol, without any isomerization of an alkenic part. The catalyst can be easily prepared from all commercially available reagents and reused several times.
- Kakiuchi,Maeda,Nishimura,Uemura
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p. 6620 - 6625
(2007/10/03)
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