- Construction of the Bicyclic Core Structure of the Enediyne Antibiotic Esperamicin-A1 in Either Enantiomeric Form from (-)-Quinic Acid
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Employed as a common chiral starting material, (-)-quinic acid (7) was converted in a concise manner to both enantiomers of the β,γ-unsaturated ketone 12.On the one hand, (+)-12 was obtained by stereospecific borohydride reduction of the conjugated ketone
- Ulibarri, Gerardo,Nadler, William,Skrydstrup, Troels,Audrain, Helene,Chiaroni, Angele,et al.
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Read Online
- Synthesis, Structure, and Tandem Mass Spectrometric Characterization of the Diastereomers of Quinic Acid
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(-)-Quinic acid possess eight possible stereoisomers, which occur both naturally and as products of thermal food processing. In this contribution, we have selectively synthesized four isomers, namely, epi-quinic acid, muco-quinic acid, cis-quinic acid, and scyllo-quinic acid, to develop a tandem LC-MS method identifying all stereoisomeric quinic acids. Four derivatives have been unambiguously characterized by single-crystal X-ray crystallography. The missing diastereomers of quinic acid were obtained by nonselective isomerization of (-)-quinic acid using acetic acid/concentrated H2SO4 allowing chromatographic separation and assignment of all diastereomers of quinic acid. We report for the first time that a full set of stereoisomers are reliably distinguishable on the basis of their tandem mass spectrometric fragment spectra as well as their elution order. A rationale for characteristic fragmentation mechanisms is proposed. In this study, we also observed that muco-quinic acid, scyllo-quinic acid, and epi-quinic acid are present in hydrolyzed Guatemalan roasted coffee sample as possible products of roasting.
- Deshpande, Sagar,Matei, Marius Febi,Jaiswal, Rakesh,Bassil, Bassem S.,Kortz, Ulrich,Kuhnert, Nikolai
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p. 7298 - 7306
(2016/10/07)
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- Novel compound, its synthetic method and therapeutic use (by machine translation)
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Novel compounds are described. The compounds generally comprise an acidic group, a basic group, a substituted amino or N-acyl and a group having an optionally hydroxylated alkane moiety. Pharmaceutical compositions comprising the inhibitors of the invention are also described. Methods of inhibiting neuraminidase in samples suspected of containing neuraminidase are also described. Antigenic materials, polymers, antibodies, conjugates of the compounds of the invention with labels, and assay methods for detecting neuraminidase activity are also described.
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Paragraph 0690; 0691; 1359-1368
(2016/10/07)
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- Stereoselective synthesis of the halaven C14-C26 fragment from D-quinic acid: Crystallization-induced diastereoselective transformation of an α-methyl nitrile
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Crystallization-induced diastereoselective transformation (CIDT) of an α-methyl nitrile completes an entirely non-chromatographic synthesis of the halichondrin B C14-C26 stereochemical array. The requisite α-methyl nitrile substrate is derived from D-quinic acid through a series of substrate-controlled stereoselective reactions via a number of crystalline intermediates that benefit from a rigid polycyclic template. Therefore, all four stereogenic centers in the Halaven C14-C26 fragment were derived from the single chiral source D-quinic acid.
- Belanger, Francis,Chase, Charles E.,Endo, Atsushi,Fang, Francis G.,Li, Jing,Mathieu, Steven R.,Wilcoxen, Annie Z.,Zhang, Huiming
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supporting information
p. 5108 - 5111
(2015/04/27)
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- Parallel synthesis and biological evolution of quinic acid derivatives as immuno-suppressing agents against T-cell receptors
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A simple protocol for the synthesis of quinic acid derivatives was established and their biological evolution against T-cells is studied. Results showed that one of the derivatives, Cyn-1324, has low toxicity on T-cells and a high effect on reducing Signal 2 of T-cell immune responses. In vitro binding measurements of atomic force spectroscopy further indicated that the blocking effect of Cyn-1324 between CD28 and CD80 was about 31 ± 4%. In vivo animal tests also confirmed that Cyn-1324 can reduce the allergic responses from ovalbumin-induced mice with little toxicity. Based on these observations, Cyn-1324 can be a mild immuno-suppressive candidate for future drug development.
- Huang, Chih-Yu,Chen, Li-Hsun,Huang, Hsuan-Yu,Kao, Feng-Sheng,Lee, Yun-Ta,Selvaraju, Manikandan,Sun, Chung-Ming,Chen, Hueih-Min
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p. 50801 - 50806
(2015/06/25)
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- Synthesis and HIV-1 inhibitory activities of dicaffeoyl and digalloyl esters of quinic acid derivatives
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Twenty analogues of the anti-HIV-1 integrase (IN) inhibitors dicaffeoylquinic acids (DCQAs) were prepared. Their IC50 values for 3'-end processing and strand transfer against recombinant HIV-1IN were determined in vitro, and their cell toxiciti
- Junior,Verde,Rezende,Caneschi,Couri,McDougall,Robinson Jr.,De Almeida
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p. 724 - 733
(2013/07/28)
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- The synthesis of 2-oxyalkyl-cyclohex-2-enones, related to the bioactive natural products COTC and antheminone A, which possess anti-tumour properties
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The syntheses of five novel 2-oxyalkyl-cyclohex-2-enones, structurally related to the natural products COTC and antheminone A, are described. The target structures were selected in order to probe the influence of several key structural parameters on in vi
- Arthurs, Claire L.,Morris, Gareth A.,Piacenti, Michela,Pritchard, Robin G.,Stratford, Ian J.,Tatic, Tanja,Whitehead, Roger C.,Williams, Katharine F.,Wind, Natasha S.
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experimental part
p. 9049 - 9060
(2011/01/04)
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- CAFFEOYL QUINIC ACID DERIVATIVES CONTAINING NITROGEN, AND PREPARATION METHOD, PHARMACEUTICALLY COMPOSITION AND USAGE THEREOF
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The present invention provides caffeoylquinic acid derivatives and a method of preparing for the same, and also provides pharmaceutical compositions containing caffeoylquinic acid derivatives, and uses of caffeoylquinic acid derivatives in preparation of
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Page/Page column 9
(2009/12/23)
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- (-)-Quinic acid: a versatile precursor for the synthesis of analogues of 2-crotonyloxymethyl-(4R,5R,6R)-4,5,6-trihydroxycyclohex-2-enone (COTC) which possess anti-tumour properties
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Syntheses of three novel analogues of the Streptomyces metabolite COTC are described, using the versatile chiral pool starting material, (-)-quinic acid. The results of bioassays of the target compounds against two lung cancer cell lines, A549 and H460, a
- Arthurs, Claire L.,Lingley, Katharine F.,Piacenti, Michela,Stratford, Ian J.,Tatic, Tanja,Whitehead, Roger C.,Wind, Natasha S.
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p. 2410 - 2413
(2008/09/18)
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- INTERMEDIATES FOR THE PREPARATION OF HALICHONDRIN B
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The present invention provides macrocyclic compounds, synthesis of the same and intermediates thereto. Such compounds, and compositions thereof, are useful for treating or preventing proliferative disorders Formula (F-4).
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Page/Page column 54
(2010/02/15)
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- [2+2] Photoadditions with chiral 2,5-cyclohexadienone synthons
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Three chiral 2,5-cyclohexadienone synthons bearing different chiral auxiliaries were examined in [2+2] photoadditions with cyclopentene. Regeneration of the 'masked' double bond in the adducts resulted in the preparation of optically active 5-4-6 adducts. The enantiomeric purity of each adduct was found to be >95% using comparative 13C NMR analysis of the appropriate ketals. The asymmetry induced in the cycloaddition step of our methodology indicated that the facial selectivity was directly correlated to the degree of steric bulk of the chiral auxiliary on the synthon.
- Lange, Gordon L.,Humber, Craig C.,Manthorpe, Jeffrey M.
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p. 1355 - 1362
(2007/10/03)
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- Synthesis of (+)-(1R,2R,4R,6S)-1,6-epoxy-4-benzyloxycyclohexan-2-ol, a key precursor to inositol monophosphatase inhibitors, from (-)-quinic acid
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A new and efficient route to homochiral (+)-(1R,2R,4R,6S)-1,6-epoxy-4-benzyloxycyclohexan-2-ol and its 2-benzyl ether derivative is described, starting from (-)-quinic acid. The compounds are key intermediates in the solution-phase and solid-phase synthesis of inhibitors for inositol monophosphatase. The pivotal step involves a La3+-induced reversal of the diastereoselectivity for the borohydride reduction of an intermediate cyclohexan-4-one. (1R,2R,4R,6R)-(O6-Propyl)cyclohexane-1,2,4,6-tetraol 1-phosphate, predicted to be a submicromolar competitive inhibitor of inositol monophosphatase, was prepared from the title epoxide in 5 steps in good overall yield. The compound proved to be a competitive inhibitor and displayed the expected potency confirming the stereochemical requirements for inhibition. The O2-benzylated epoxide derivative could be stereospecifically alcoholysed using either BF3·(OEt)2 or Yb(III)(OTf)3 as catalysts without appreciable levels of benzyl ether protecting group cleavage. The preparation of the alcoholysis products (1S,2R,4S,6R)-2,4-bis(benzyloxy)-6-isopropyloxycyclohexanol and (1S,2R,4S,6R)-2,4-bis(benzyloxy)-6-(phenethyloxy)cyclohexanol, and the synthesis and evaluation of the inhibitor (1R,2R,4R,6R,2′S)-6-(1′-hydroxy-3′-phenylpropan-2-yloxy)-2,4-d ihydroxycyclohexyl phosphate and its diastereomer (1R,2R,4R,6R,2′R)-6-(1′-hydroxy-3′-phenylpropan-2-yloxy)-2,4-d ihydroxycyclohexyl phosphate are described.
- Schulz, Juergen,Beaton, Martin W.,Gani, David
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p. 943 - 954
(2007/10/03)
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- Synthesis of α-trinositol analogues derived from D-(-)-quinic acid as affinity probe precursors
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D-(-)-Quinic acid was appropriately protected to permit the phosphorylation of the three vicinal hydroxyl groups. Final deprotection lead to tris(phosphates) possessing the same configuration as the parent α-trinositol and an arm suitable for the attachement of a photoactivable group.
- Guédat,Rehnberg,Spiess,Schlewer
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p. 553 - 554
(2007/10/03)
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- Synthesis of (-)-(1R,2R,4R,6S)-1,6-epoxy-4-benzyloxycyclohexan-2-ol, a key precursor to inositol monophosphatase inhibitors, from (-)-quinic acid
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A new and efficient route to (-)-(1R,2R,4R,6S)-1,6-epoxy-4-benzyloxycyclohexan-2-ol is described starting from (-)-quinic acid. The pivotal step involves a La3+-induced reversal of the diastereoselectivity for the borohydride reduction of an intermediate cyclohexan-4-one. (1R,2R,4R,6R)-6-Propyloxycyclohexan-1,2,4-triol 1-phosphate, predicted to be a submicromolar inhibitor of inositol monophosphatase, was prepared from the epoxide in 20% yield and displayed the expected potency.
- Schulz, Juergen,Gani, David
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p. 111 - 114
(2007/10/03)
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- Chlorogenic acid and synthetic chlorogenic acid derivatives: Novel inhibitors of hepatic glucose-6-phosphate translocase
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The enzyme system glucose-6-phosphatase (EC 3.1.3.9) plays a major role in the homeostatic regulation of blood glucose. It is responsible for the formation of endogenous glucose originating from gluconeogenesis and glycogenolysis. Recently, chlorogenic acid was identified as a specific inhibitor of the glucose-6-phosphate translocase component (Gl-6-P translocase) of this enzyme system in microsomes of rat liver. Glucose 6- phosphate hydrolysis was determined in the presence of chlorogenic acid or of new synthesized derivatives in intact rat liver microsomes in order to assess the inhibitory potency of the compounds on the translocase component. Variation in the 3-position of chlorogenic acid had only poor effects on inhibitory potency. Introduction of lipohilic side chain in the 1-position led to 100-fold more potent inhibitors. Functional assays on isolated perfused rat liver with compound 29i, a representative of the more potent derivatives, showed a dose-dependent inhibition of gluconeogenesis and glycogenolyosis, suggesting glucose-6-phosphatase as the locus of interference of the compound for inhibition of hepatic glucose production also in the isolated organ model. Gl-6-P translocase inhibitors may be useful for the reduction of inappropriately high rates of hepatic glucose output often found in non-insulin-dependent diabetes.
- Hemmerle, Horst,Burger, Hans-Joerg,Below, Peter,Schubert, Gerrit,Rippel, Robert,Schindler, Peter W.,Paulus, Erich,Herling, Andreas W.
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p. 137 - 145
(2007/10/03)
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- Synthesis of a key intermediate for the synthesis of (+)-grandisol utilizing (-)-quinic acid
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A key intermediate for the synthesis of (+)-grandisol, (4aR,6aR)-4a- methyl-2-oxabicyclo[4.2.0]octan-1-one, was synthesized starting from (-)- quinic acid as the chiral source.
- Matsuo, Keizo,Morita, Masakatsu,Kawashima, Ken-Ichi
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p. 1734 - 1738
(2007/10/03)
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- (-)-Quinic Acid in Organic Synthesis. Part 4. Syntheses of Cyclophellitol and its (1R,6S)-, (2S)-, (1R,2S,6S)-Diastereoisomers
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Cyclophellitol 1 and its (1R,6S)-, (2S)-, (1R,2S,6S)-diastereoisomers 2, 3 and 4 are constructed from quinic acid involving the following key steps: regioselective cyclic sulfate ring opening, regiospecific oxidative elimination and an epoxidation.Diastereoisomers 1, 2, 3 and 4 are characterized as their corresponding tetraacetates 5, 6, 7 and 8.
- Shing, Tony K. M.,Tai, Vincent W.-F.
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p. 2017 - 2026
(2007/10/02)
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- 6-Fluoro-shikimic acid derivatives, pharmaceutical compositions and use as antibacterials and fungicides
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6-Fluoroshikimic acid derivatives of the formula (I): STR1 wherein R1 is hydroxy or a moiety biotransformable thereto and R2 is hydrogen or --P(O)(OH)2 have antibacterial, antifungal, and herbicidal activity. Their preparation and use are described as are pharmaceutical compositions containing them.
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- Studies Related to Cyclopentanoid Natural Products. Part 2. An Improved Route to (4R)-4-Hydroxy-2-hydroxymethylcyclopent-2-en-1-one and its O-Substituted Derivatives
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(3R,4S,5R)-3,4-O-Cyclohexylidene-3,4,5-trihydroxycyclohexan-1-one (11a), prepared from D-quinic acid (4a) by a published three-step sequence, was converted into the 5-O-benzoyl derivative (11b) by the action of benzoyl chloride.Simultaneous protection of the ketonic carbonyl group and removal of the cyclohexylidene moiety occurred when the compound (11b) was treated with ethane-1,2-dithiol and boron trifluoride-diethyl ether.The derived (7R,8R,9R)-9-benzoyloxy-7,8-dihydroxy-1,4-dithiaspirodecane (15a), when treated sequentially with lead(IV) acetate and pyrrolidinium acetate, underwent an oxidative ring contraction to give (8R)-8-benzoyloxy-1,4-dithiaspironon-6-ene-6-carbaldehyde (17a). The aldehyde (17a) reacted with lithium aluminium hydride to give (8R)-8-hydroxy-6-hydroxymethyl-1,4-dithiaspironon-6-ene (18a) and with sodium cyanoborohydride to yield (8R)-8-benzoyloxy-6-hydroxymethyl-1,4-dithiaspironon-6-ene (18b).Sodium methoxide effected the transformation of the hydroxybenzoate (18b) into the diol (18a) which underwent benzylation with benzyl bromide to give the dibenzyl ether (18c).Benzoylation of the hydroxybenzoate (18b), to give the dibenzoate (18d), was achieved by the action of benzoyl chloride.Removal of the dithiolane moiety from compounds (18a-d), to give the cyclopent-2-en-1-ones (1a-d), was brought about by copper(II) chloride-copper(II) oxide. The cyclohexanone (11b) also reacted with propane-1,3-dithiol and boron trifluoride-diethyl ether to give (8R,9R,10R)-10-benzoyloxy-8,9-dihydroxy-1,5-dithiaspiroundecane (20), which underwent an oxidative ring contraction to (9R)-9-benzoyloxy-1,5-dithiaspirodec-7-ene-7-carbaldehyde (22) when treated with lead(IV) acetate followed by dibenzylamine trifluoroacetate. The outcome of the reaction of the cyclohexanone (11b) with ethane-1,2-diol depended upon the reaction conditions.In refluxing benzene and in the presence of toluene-p-sulphonic acid, 1-hydroxy-4-(2-hydroxyethoxy)benzene (24) was formed.At room temperature and in the presence of sulphuric acid, (7R,8R,9R)-9-benzyloxy-7,8-dihydroxy-1,4-dioxaspirodecane (15c) was the major product.Although the oxidative ring contraction of the last-mentioned derivative was also effected by the action of lead(IV) acetate followed by dibenzylamine trifluoroacetate, the resultant (8R)-8-benzoyloxy-1,4-dioxaspironon-6-ene-6-carbaldehyde (17c) was an unstable entity. Compounds (17a) and (22) inhibited the growth of Staphylococcus aureus at concentrations of 2 and 32 μg cm-3, respectively.
- Elliott, John D.,Kelson, Andrew B.,Purcell, Neil,Stoodley, Richard J.,Palfreyman, Malcolm N.
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p. 2441 - 2449
(2007/10/02)
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