- PROCESS FOR PREPARING HEPARINOIDS AND INTERMEDIATES USEFUL IN THE SYNTHESIS THEREOF
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Processes are disclosed for the synthesis of the Factor Xa anticoagulant fondaparinux and related compounds. Protected pentasaccharide intermediates and efficient and scalable processes for the industrial scale production of fondaparinux sodium by conversion of the protected pentasaccharide intermediates via a sequence of deprotection and sulfonation reactions are provided.
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- AN EFFICIENT AND SCALABLE PROCESS FOR THE MANUFACTURE OF FONDAPARINUX SODIUM
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The present invention relates to a process for the synthesis of the Factor Xa anticoagulent Fondaparinux and related compounds. The invention relates, in addition, to efficient and scalable processes for the synthesis of various intermediates useful in the synthesis of Fondaparinux and related compounds.
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- Structure and stereochemistry of an anti-inflammatory anhydrosugar from the Australian marine sponge Plakinastrella clathrata and the synthesis of two analogues
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The structure and relative/absolute configuration of the C-15:0 iso-branched fatty acyl 1,6-anhydropyranose 1 isolated from the Australian marine sponge Plakinastrella clathrata have been investigated. Synthesis of the C-16:0 side chain-modified analogues
- Katavic, Peter L.,Yong, Ken W.L.,Herring, Joel N.,Deseo, Myrna A.,Blanchfield, Joanne T.,Ferro, Vito,Garson, Mary J.
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p. 8074 - 8079
(2013/08/23)
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- N-O bond as a glycosidic-bond surrogate: Synthetic studies toward polyhydroxylated N-alkoxypiperidines
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A series of novel polyhydroxylated N-alkoxypiperidines has been synthesized by ring-closing double reductive amination (DRA) of highly functionalized 1,5-dialdehydes with various hydroxylamines. The required saccharide-based dialdehydes were prepared efficiently from sodium cyclopentadienylide in seven steps. A two-step protocol has been developed for the DRA; it led, after deprotection, to isofagomine, 3-deoxyisofagomine, and numerous other N-alkoxy analogues. The barrier to inversion in these polyhydroxylated N-alkoxypiperidine derivatives was found by variable-temperature NMR methods to be approximately 15 kcal mol-1. With the exception of N-hydroxyisofagomine itself, none of the compounds prepared showed significant inhibitory activity against sweet almond β-glucosidase. Copyright
- Malik, Ga?lle,Ferry, Angélique,Guinchard, Xavier,Cresteil, Thierry,Crich, David
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supporting information
p. 2168 - 2179
(2013/03/29)
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- EFFICIENT AND SCALABLE PROCESS FOR THE MANUFACTURE OF FONDAPARINUX SODIUM
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The present invention relates to a process for the synthesis of the Factor Xa anticoagulent Fondaparinux and related compounds. The invention relates, in addition, to efficient and scalable processes for the synthesis of various intermediates useful in the synthesis of Fondaparinux and related compounds.
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- Total synthesis of n-acetylglucosamine-1,6-anhydro-n- acetylmuramylpentapeptide and evaluation of its turnover by ampd from escherichia coli
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The bacterial cell wall is recycled extensively during the course of cell growth. The first recycling event involves the catalytic action of thelytic transglycosylase enzymes, which produce an uncommon 1,6-anhydropy ranose moiety during separation of the muramyl residues from the peptidoglycan, the major constituent of the cell wall. This product, an N-acetyl-β-D-glucosamine- (1→4)-1,6-anhydro-N-acetyl-β-Dmuramylpeptide, is either internalized to initiate the recycling process or diffuses into the milieu to cause stimulation of the pro-inflammatory responses by the host. We report the total syntheses of N-acetyl-β-Dglucosamine-( 1→4)-1,6-anhydro-N-acetyl- β-D-muramyl-L-Ala-γ-D-Glu-meso-DAP-D-Ala-D-Ala (compound 1, the product of lytic transglycosylase action on the cell wall of Gram-negative bacteria) and N-acetyl-β-Dglucosamine-( 1→4)-1,6-anhydro-N-acetyl- β-D-muramyl-L-Ala-γ-D-Glu-L-Lys-D-Ala-D-Ala (compound 2, from lytic transglycosylase action on the cell wall of Gram-positive bacteria). The syntheses were accomplished in 15 linear steps. Compound 1 is shown to be a substrate of the AmpD enzyme of the Gram-negative bacterium Escherichia coli, anenzyme that removes the peptide from the disaccharide scaffold in the e arly cytoplasmic phase of cell wall turnover.
- Hesek, Dusan,Lee, Mijoon,Zhang, Weilie,Noll, Bruce C.,Mobashery, Shahriar
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supporting information; experimental part
p. 5187 - 5193
(2009/09/30)
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- Synthesis of a heparan sulfate mimetic disaccharide with a conformationally locked residue from a common intermediate
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A simple mimetic of a heparan sulfate disaccharide sequence that binds to the growth factors FGF-1 and FGF-2 was synthesized by coupling a 2-azido-2-deoxy-d-glucopyranosyl trichloroacetimidate donor with a 1,6-anhydro-2-azido-2-deoxy-β-d-glucopyranose acceptor. Both the donor and acceptor were obtained from a common intermediate readily obtained from d-glucal. Molecular docking calculations showed that the predicted locations of the disaccharide sulfo groups in the binding site of FGF-1 and FGF-2 are similar to the positions observed for co-crystallized heparin-derived oligosaccharides obtained from published crystal structures.
- Fairweather, Jon K.,Karoli, Tomislav,Liu, Ligong,Bytheway, Ian,Ferro, Vito
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experimental part
p. 2394 - 2398
(2010/01/03)
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- NOVEL ANTI-INFLAMMATORY PRO-DRUGS
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The present invention relates to compounds according to formula (I): wherein R is selected from the group consisting of anti-inflammatory agents and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising compounds of formula (I) and the use of these pharmaceutical compositions for the treatment or prophylaxis of chronic inflammatory diseases, in particular those that are caused by chronically activated macrophages. The chronic inflammatory disease is in particular atherosclerosis, (rheumatoid) arthritis, an (auto)immune disease or sarcoidosis.
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Page/Page column 17-18
(2009/01/24)
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- Investigation of the hydrogen bonding properties of a series of monosaccharides in aqueous media by 1H NMR and IR spectroscopy
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A technique, based on 1H NMR and IR experiments, to characterise intramolecular hydrogen bonds in aqueous medium in a series of amino, amido and ammonium sugar derivatives has been established. Three groups of molecules, representing amides (4, 5 and 6), amines (7 and 8) and ammonium salts (chlorides 9 and 10, and phosphates 11 and 12), with different relative configurations of their functional groups, have been investigated to assess the effect of the nature and the stereochemistry of these groups on the hydrogen-bonding features of the sugar. The deduced features in water solution are compared to those obtained previously in nonpolar solvents. The phosphate salts of amines 7 and 8 (11 and 12) were also prepared, in order to evaluate the influence of the OH groups on the binding of the phosphate counterion, and the possibility of establishing cooperative hydrogen bonds involving the phosphate group. The data presented here indicate that the 1,3-cis-diaxial-type configuration in sugar diols and amino alcohols produces an intramolecular six-membered-ring hydrogen bond that survives in water and, moreover, offers the possibility to establish cooperative intermolecular hydrogen bonds. Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.
- Hawley, Joanne,Bampos, Nick,Aboitiz, Nuria,Jimenez-Barbero, Jesus,Lopez De La Paz, Manuela,Sanders, Jeremy K. M.,Carmona, Pedro,Vicent, Cristina
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p. 1925 - 1936
(2007/10/03)
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- An electrophile-mediated cyclization on the 1,6-anhydro-D-glucopyranose framework
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Iodocyclization of O-tributylstannyl-D-glucal with iodine in acetonitrile gave 1,6-anhydro-2-deoxy-2-iodo-β-D-glucopyranose (1) in high yield.The 3,4-di-O-acetyl derivative of 1 could be converted into the corresponding 2-deoxy compound and into the 2-C-allyl-2-deoxy branched sugar (5) by treatment with tributylstannane and allyltributylstannane, respectively.Controlled alkaline hydrolysis of 5 gave the 4-monoacetyl derivative.Complete hydrolysis of 5 gave the 3,4-diol, which underwent a 5-exo cyclization by treatment with N-bromosuccinimide. 1H NMR spectroscopy and X-ray analysis showed that the cyclized product has the B3,0 conformation in its pyranose ring, which is trans-fused to the newly formed tetrahydrofuran ring.
- Leteux, Christine,Veyrieres, Alain,Robert, Francis
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p. 119 - 130
(2007/10/02)
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- Versatile Behavior of O-Stannylated D-Glucal Towards Halogens
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O-Tributylstannyl-D-glucal undergoes allylic oxidation when treated with N-iodosuccinimide (NIS) in benzene, whereas oxidative 1,6-halocyclization occurs with NIS in acetonitrile or molecular halogens in various solvents.Key Words: tributyltin ethers; D-glucal; allylic oxidation; halocylization; bicyclic synthons
- Czernecki, Stanislas,Leteux, Christine,Veyrieres, Alain
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p. 221 - 224
(2007/10/02)
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- An Expeditious and Stereocontrolled Preparation of 2-Azido-2-deoxy-β-D-glucopyranose Derivatives from D-Glucal
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1,6-Anhydro-2-azido-2-deoxy-β-D-glucopyranose has been prepared by a two-step procedure from D-glucal and transformed into precursors useful in the synthesis of oligosaccharides.
- Tailler, Denis,Jaquinet, Jean-Claude,Noirot, Anne-Marie,Beau, Jean-Marie
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p. 3163 - 3164
(2007/10/02)
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