- Asymmetric synthesis of long chain β-hydroxy fatty acid methyl esters as new elastase inhibitors
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Herein, β-hydroxy methyl esters with an even carbon chain length of 12-20 1b-5b were synthesized by three different asymmetric reduction methods I, II III from their corresponding β-keto methyl esters 1a-5a with the aim of determining their elastase activities. In method I, chiral catalyst A was prepared from chiral ligand (R)-binaphthol 1, while in method II, chiral catalyst B was synthesized from (2R,3R)-diisopropyl tartrate 2. Chiral catalyst B has not previously been used in asymmetric borane reductions or in the asymmetric synthesis of chiral β-hydroxy methyl esters. In method III, an asymmetric reduction was catalysed by (R)-Me-CBS oxazaborolidine 3. Hydride transfer was carried out in all of these methods by BH3· SMe2. Chiral hydroxy methyl esters with an (S)-configuration were synthesized by method I and with an (R)-configuration via methods II and III. The chiral hydroxy methyl esters obtained were analysed by chiral HPLC for their ee % values. Methods I, II and III were applied to long chain β-keto methyl esters for the first time. The reduction methods I, II and III were examined in terms of reaction yield and enantiomeric excess according to carbon chain length and the variable ratio of chiral catalysts to β-keto methyl ester. The highest enantiomeric excess of 90% ee was found in method III for 12 and 14 carbon numbers.
- Hasdemir, Belma,Onar, Huelya Elik,Yusufolu, Aye
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p. 1100 - 1105
(2012/11/07)
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- Chemical Synthesis of helicobacter pylori lipopolysaccharide partial structures and their selective proinflammatory responses
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Helicobacter pylori is a common cause of gastroduodenal inflammatory diseases such as chronic gastritis and peptic ulcers and also an important factor in gastric carcinogenesis. Recent reports have demonstrated that bacterial inflammatory processes, such as stimulation with H. pylori lipopolysaccharide (LPS), initiate atherosclerosis. To establish the structures responsible for the inflammatory response of H. pylori LPS, we synthesized various kinds of lipid A structures (i.e., triacylated lipid A and Kdo-lipid A compounds), with or without the ethanolamine group at the 1-phosphate moiety, by a new divergent synthetic route. Stereoselective α-glycosylation of Kdo N-phenyltrifluoroacetimidate was achieved by use of microfluidic methods. None of the lipid A and Kdo-lipid A compounds were a strong inducer of IL-1β, IL-6, or IL-8, suggesting that H. pylori LPS is unable to induce acute inflammation. In fact, the lipid A and Kdo-lipid A compounds showed antagonistic activity against cytokine induction by E. coli LPS, except for the lipid A compound with the ethanolamine group, which showed very weak agonistic activity. On the other hand, these H. pylori LPS partial structures showed potent IL-18- and IL-12-inducing activities. IL-18 has been shown to correlate with chronic inflammation, so H. pylori LPS might be implicated in the chronic inflammatory responses induced by H. pylori. These results also indicated that H. pylori LPS can modulate the immune response: NF-κB activation through hTLR4/MD-2 was suppressed, whereas production of IL-18 and IL-12 was promoted.
- Shimoyama, Atsushi,Saeki, Akinori,Tanimura, Natsuko,Tsutsui, Hiroko,Miyake, Kensuke,Suda, Yasuo,Fujimoto, Yukari,Fukase, Koichi
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supporting information; experimental part
p. 14464 - 14474
(2012/02/04)
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- 2-Acety-1-(3-glycosyloxyoctadecanoyl)glycerol and dammarane triterpenes in the exudates from glandular trichome-like secretory organs on the stipules and leaves of Cerasus yedoensis
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A glycolipid, 2-acetyl-1-{3-[3,4-di-O-acetyl-β-d-glucopyranosyl-(1 → 3)-2-O-acetyl-α-l-rhamnopyranosyloxy]octadecanoyl}-sn-glycerol (1) and a dammarane triterpene, (2α,20S)-2,20-dihydroxydammar-24-en-3-one (2), along with known (20S)-20-hydroxydammar-24-en-3-one (3), were isolated from the exudates of the glandular trichome-like secretory organs in the young stipules and leaves of Cerasus yedoensis (Rosaceae).
- Asai, Teigo,Fujimoto, Yoshinori
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experimental part
p. 38 - 42
(2012/05/04)
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- Asymmetric synthesis of sphinganine and clavaminol H
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(Figure presented) An efficient enantioselective synthesis of sphinganine and clavaminol H is reported. These sphingoid-type bases were obtained from commercially available fatty acids using highly enantioselective Ru-catalyzed hydrogenation and organocatalytic electrophilic amination reactions to create the stereogenic centers.
- Ait-Youcef, Ramzi,Moreau, Xavier,Greck, Christine
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experimental part
p. 5312 - 5315
(2010/10/19)
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- Enantioselective Hydrogenation of β-Keto Esters using Chiral Diphosphine-Ruthenium Complexes: Optimization for Academic and Industrial Purposes and Synthetic Applications
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Enantioselective hydrogenation using chiral complexes between atropisomeric diphosphines and ruthenium is a powerful tool for producing chiral compounds. Using a simple and straightforward in situ catalyst preparation, the conditions were optimized using molecular hydrogen for both academic and industrial purposes. This led to the best conditions and the lowest catalytic ratio required for the pressure used. Hydrogenation of various β-keto esters was efficiently performed at atmospheric and higher pressures, leading to the use of very low catalyst-substrate ratios up to 1/20,000. Asymmetric hydrogenations were used in key-steps towards the total synthesis of corynomycolic acid, Duloxetine and Fluoxetine.
- Ratovelomanana-Vidal,Girard,Touati,Tranchier,Ben Hassine,Genet
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p. 261 - 274
(2007/10/03)
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- Process for producing optically active alcohol
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A novel process in which an optically active alcohol compound having a desired absolute configuration and a high optical purity can be obtained by asymmetrically hydrogenating a β-keto acid compound through a simple operation. An optically active alcohol represented by the following general formula (III) : (wherein R1 represents a C1-C15 alkyl group which may have one or more substituents (selected from halogen atoms, a hydroxyl group, an amino group, amino groups protected by a protective group, amino groups protected by a mineral acid or organic acid, amino groups substituted with one or more C1-C4 lower alkyl groups, a benzyloxy group, C1-C4 lower alkoxy groups, C1-C4 lower alkoxycarbonyl groups, and aryl groups) or an aryl group; and R2 represents a C1-C8 lower alkyl group, or a benzyl group which may have one or more substituents) is obtained by asymmetrically hydrogenating a β-keto ester compound represented by the following general formula (I): (wherein R1 and R2 are the same as defined above) in the presence of at least one ruthenium complex having as a ligand an optically active tertiary diphosphine compound represented by the following general formula (II): (wherein R3 and R4 each independently represent a cycloalkyl group, an unsubstituted or substituted phenyl group, or a five-membered heteroaromatic ring residue).
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- Asymmetric hydrogenation reactions using a practical in situ generation of chiral ruthenium-diphosphine catalysts from anhydrous RuCl3
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A very simple in situ preparation of chiral ruthenium-diphosphine catalyst from anhydrous RuCl3 is reported. Prochiral C = O and C = C bonds have been reduced with high enantioselectivities via ruthenium-catalyzed hydrogenation.
- Madec,Pfister,Phansavath,Ratovelomanana-Vidal,Genêt
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p. 2563 - 2568
(2007/10/03)
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- Optically active compound and process for producing the same
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An optically active (2S,3R)-2-(3'-hydroxyacyl)aminoalkane-1,3-diol and a process for producing the same are disclosed. The compound is represented by the following general formula (1): STR1 wherein R1 represents a linear or branched, saturated aliphatic hydrocarbon group having 9 to 19 carbon atoms; R2 represents a linear or branched, saturated aliphatic hydrocarbon group having 1 to 19 carbon atoms; and symbol * means that the carbon atom is an asymmetric carbon atom of the S or R configuration. The optically active compound is a ceramide in which the fatty acid moiety has an optically active hydroxyl group in the 3-position.
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- Optically active ceramides and process for producing the same
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An optically active (2S,3R)-2-(3'-hydroxyacyl)aminoalkane-1,3-diol and a process for producing the same are disclosed. The compound is represented by the following general formula (1): wherein R1represents a linear or branched, saturated aliphatic hydrocarbon group having 9 to 19 carbon atoms; R2represents a linear or branched, saturated aliphatic hydrocarbon group having 1 to 19 carbon atoms; and symbol * means that the carbon atom is an asymmetric carbon atom of the S or R configuration. The optically active compound is a ceramide in which the fatty acid moiety has an optically active hydroxyl group in the 3-position.
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- Properties of unusual phospholipids. III: Synthesis, monolayer investigations and DSC studies of hydroxy octadeca(e)noic acids and diacylglycerophosphocholines derived therefrom
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Diacylglycerophosphocholines containing (R)-3-, (R)-12-, (R)-17-hydroxy octadeca(e)noic acids and the corresponding racemates were synthesized and purified to homogeneity. The influence of the position of the hydroxy group on the monolayer packing properties of these fatty acids and their phosphatidylcholines was studied by Langmuir techniques and 1,2-di-[(R)-12-hydroxy-octadec-cis-9-enyl]-sn-glycero-3-phosphocholine displayed the largest lift-off area (330 A2/molecule). This result was in line with the thermotropic phase behavior of these phospholipids, as measured by differential scanning calorimetry (DSC): the gel- to liquid-crystalline phase transition temperature (T(m))passed through a minimum of -15.1°C for 1,2-di-[(R)-12-hydroxy-octadec-cis-9-enyl]-sn-glycero-3-phosphocholine.
- Negelmann, Lars,Pisch, Sandra,Bornscheuer, Uwe,Schmid, Rolf D.
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p. 117 - 134
(2007/10/03)
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- ENANTIOSELECTIVE HYDROGENATION REACTIONS WITH A FULL SET OF PREFORMED AND PREPARED IN SITU CHIRAL DIPHOSPHINE-RUTHENIUM (II) CATALYSTS
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The new class of 2-methylallyl ruthenium chiral diphosphines 1 are efficient in asymmetric hydrogenation of α,β unsaturated acids and allylic alcohols.The related chiral halogen-containing ruthenium catalysts 2 are prepared from 1 or in situ from (COD)Ru(η3-(CH2)2CHCH3)2 by ligand exchange with the chelating diphosphine followed by protonation (HX) in acetone.This procedure allows rapid screening of chiral phosphines, such as Diop, Chiraphos, Cbd, Bppm, Binap, β-glucophos, Biphemp, MeO-Biphep, Me-Duphos, in ruthenium mediated hydrogenations of prochiral substrates.A high efficiency is displayed by Ru-catalysts having atropisomeric ligands (e.e. up to 99percent), and a C2 symmetric bis(phospholane) has also emerged as a valuable ligand (Me-Duphos, e.e. up to 87percent not optimized).Asymmetric hydrogenation of β-keto esters can be conducted under quite mild conditions (4 atm. of H2, 50 deg C, e.e. up to 99percent), β-keto esters having a disubstituted double bond are also hydrogenated chemoselectively to unsaturated chiral alcohols under controlled conditions with excellent optical purities.
- Genet, J. P.,Pinel, C.,Ratovelomanana-Vidal, V.,Mallart, S.,Pfister, X.,et al.
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p. 675 - 690
(2007/10/02)
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- Asymmetric Reduction of Aliphatic Short- to Long-Chain β-Keto Acids by Use of Fermenting Bakers' Yeast
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Eleven β-keto acids, ranging from 3-oxobutanoic to 3-oxooctanoic acids, were reduced with fermenting bakers' yeast to the corresponding optically active β-hydroxy acids, which were isolated as the methyl esters.In all cases, the (R)-hydroxy acids were obtained in >/=98percent ee, except for 3-oxobutanoic acid, which afforded the (S)-hydroxy acid in 86percent ee.Inhibition of fermentation was observed for 3-oxoundecanoic to 3-oxotetradecanoic acids, leading to no reduction.Lowering of the substrate concentration was found to be appreciably effective in avoiding inhibition.
- Utaka, Masanori,Watabu, Hisashi,Higashi, Hiroshi,Sakai, Takashi,Tsuboi, Sadao,Torii, Sigeru
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p. 3917 - 3921
(2007/10/02)
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- BIOCATALYTIC RESOLUTION OF LONG-CHAIN 3-HYDROXYALKANOIC ESTERS
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Enzymatic resolution of 3-butanoyloxyalkanoates of various chain length using Geotrichum candidum lipase led to optically active 3-hydroxyalkanoates.
- Feichter, C.,Faber, K.,Griengl, H.
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p. 551 - 552
(2007/10/02)
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- A General Method for the Synthesis of Both Enantiomers of Optically Pure β-Hydroxy Esters from (S)-(p-Chlorophenylsulfinyl)acetone Easily Obtainable by Kinetic Resolution with Bakers' Yeast
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Both enantiomers of various optically pure (R)- and (S)-β-hydroxy esters were generally synthesized from (S)-(p-chlorophenylsulfinyl)acetone obtained by kinetic resolution with bakers' yeast, followed by γ-alkylation, diastereoselective reduction, subsequent introduction of ester group and reductive elimination of the sulfinyl group.The key step of the diastereoselective reduction of (S)-β-keto sulfoxides was performed with diisobutylaluminum hydride to give (R)C-(S)S-β-hydroxy sulfoxides or after complexation with zinc chloride followed by addition of diisobutylaluminum hydride to give (S)C-(S)S-β-hydroxy sulfoxides which were easily separated in an optically pure form by easy crystallization or separation by silica-gel chromatography due to the p-chlorophenyl moiety in the β-hydroxy sulfoxides.The utility of the present method could be successfully demonstrated in the synthesis of both (+)- and (-)-corynomycolic acids from optically pure methyl esters of (R)- and (S)-3-hydroxyoctadecanoic acid by alkylation with tetradecyl iodide at α-position and hydrolysis.
- Fujitsawa, Tamotsu,Fujimura, Atsushi,Sato, Toshio
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p. 1273 - 1280
(2007/10/02)
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- Asymmetric Reduction of 3-Oxo-octadecanoic Acid with Fermenting Baker's Yeast. An Easy Synthesis of Optically Pure (+)-(2R,3R)-Corynomycolic Acid
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Optically pure (+)-corynomycolic acid has been synthesized from methyl acetoacetate by a route including asymmetric reduction of 3-oxo-octadecanoic acid with baker's yeast as a key step.
- Utaka, Masanori,Higashi, Hiroshi,Takeda, Akira
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p. 1368 - 1369
(2007/10/02)
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