- Addressing the Structural Complexity of Fluorinated Glucose Analogues: Insight into Lipophilicities and Solvation Effects
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In this work, we synthesized all mono-, di-, and trifluorinated glucopyranose analogues at positions C-2, C-3, C-4, and C-6. This systematic investigation allowed us to perform direct comparison of 19F resonances of fluorinated glucose analogues and also to determine their lipophilicities. Compounds with a fluorine atom at C-6 are usually the most hydrophilic, whereas those with vicinal polyfluorinated motifs are the most lipophilic. Finally, the solvation energies of fluorinated glucose analogues were assessed for the first time by using density functional theory. This method allowed the log P prediction of fluoroglucose analogues, which was comparable to the C log P values obtained from various web-based programs.
- St-Gelais, Jacob,C?té, émilie,Lainé, Danny,Johnson, Paul A.,Giguère, Denis
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supporting information
p. 13499 - 13506
(2020/10/02)
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- Solid-Phase Synthesis of Fluorinated Analogues of Glycosyl 1-Phosphate Repeating Structures from Leishmania using the Phosphoramidite Method
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Bacterial and protozoan sugar chains contain glycosyl 1-phosphate repeating structures; these repeating structures have been studied for vaccine development. The fluorinated analogues of [β-Gal-(1→4)-α-Man-(1→6)-P-]n, which are glycosyl 1-phosphate repeating structures found in Leishmania, were synthesised using the solid-phase phosphoramidite method. This method has been less extensively studied for the synthesis of glycosyl 1-phosphate units than H-phosphonate chemistry. A stepwise synthesis of a compound containing five such repeating units has been conducted using the phosphoramidite method herein, which is the longest glycosyl 1-phosphate structures to be chemically constructed in a stepwise manner.
- Hara, Rintaro Iwata,Yaoita, Aya,Takeda, Katsuya,Ueki, Hiroaki,Ishii, Ayumu,Imoto, Hideyuki,Kobayashi, Satoshi,Sano, Michi,Noro, Mihoko,Sato, Kazuki,Wada, Takeshi
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p. 439 - 446
(2018/05/04)
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- Solid-supported reagents composed of a copolymer possessing 2-O-sulfonyl mannosides and phase-transfer catalysts for the synthesis of 2-fluoroglucose
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We described the synthesis of a solid-supported co-polymer possessing mannosides and phase-transfer catalysts and synthesis of 2-fluoroglucoside from it. We first prepared a soluble copolymer from two allene monomers possessing a precursor for the synthesis of 2-fluoroglycose and a crown ether. The copolymerization of the monomers via the π-ally nickel-catalyst smoothly proceeded at room temperature to provide a desired copolymer without decomposition of the sulfonate esters. The copolymer exhibited high reactivity towards fluorination in comparison with a conventional precursor. We next synthesized the solid-supported copolymer by using the solid-supported initiator attached with TentaGel resins. TentaGel enabled polymerization under stirring with stirring bar without decomposition. The solid-supported copolymer exhibited comparable reactivity towards fluorination in comparison with the soluble copolymer. In addition, it can be easily separated from the reaction vessel by filtration.
- Takeuchi, Ryota,Sakai, Yuki,Tanaka, Hiroshi,Takahashi, Takashi
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supporting information
p. 5500 - 5503
(2015/11/18)
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- METHOD FOR PRODUCING 18F-LABELED COMPOUND AND HIGH MOLECULAR COMPOUND TO BE USED IN THE METHOD
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The present invention aims at solving the problems of conventional methods for producing an 18F-labeled compound, that is, the problem of purification of a compound in a liquid phase synthesis method and the problem of an insufficient yield due
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Page/Page column 22
(2013/02/28)
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- Sialidase substrate specificity studies using chemoenzymatically synthesized sialosides containing C5-modified sialic acids
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para-Nitrophenol-tagged sialyl galactosides containing sialic acid derivatives in which the C5 hydroxyl group of sialic acids was systematically substituted with a hydrogen, a fluorine, a methoxyl or an azido group were successfully synthesized using an efficient chemoenzymatic approach. These compounds were used as valuable probes in high-throughput screening assays to study the importance of the C5 hydroxyl group of sialic acid in the recognition and the cleavage of sialoside substrates by bacterial sialidases.
- Cao, Hongzhi,Li, Yanhong,Lau, Kam,Muthana, Saddam,Yu, Hai,Cheng, Jiansong,Chokhawala, Harshal A.,Sugiarto, Go,Zhang, Lei,Chen, Xi
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scheme or table
p. 5137 - 5145
(2010/04/03)
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- Molecular recognition in the P2Y14 receptor: Probing the structurally permissive terminal sugar moiety of uridine-5′-diphosphoglucose
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The P2Y14 receptor, a nucleotide signaling protein, is activated by uridine-5′-diphosphoglucose 1 and other uracil nucleotides. We have determined that the glucose moiety of 1 is the most structurally permissive region for designing analogues of this P2Y14 agonist. For example, the carboxylate group of uridine-5′-diphosphoglucuronic acid proved to be suitable for flexible substitution by chain extension through an amide linkage. Functionalized congeners containing terminal 2-acylaminoethylamides prepared by this strategy retained P2Y14 activity, and molecular modeling predicted close proximity of this chain to the second extracellular loop of the receptor. In addition, replacement of glucose with other sugars did not diminish P2Y14 potency. For example, the [5′′]ribose derivative had an EC50 of 0.24 μM. Selective monofluorination of the glucose moiety indicated a role for the 2′′- and 6′′-hydroxyl groups of 1 in receptor recognition. The β-glucoside was twofold less potent than the native α-isomer, but methylene replacement of the 1′′-oxygen abolished activity. Replacement of the ribose ring system with cyclopentyl or rigid bicyclo[3.1.0]hexane groups abolished activity. Uridine-5′-diphosphoglucose also activates the P2Y2 receptor, but the 2-thio analogue and several of the potent modified-glucose analogues were P2Y14-selective.
- Ko, Hyojin,Das, Arijit,Carter, Rhonda L.,Fricks, Ingrid P.,Zhou, Yixing,Ivanov, Andrei A.,Melman, Artem,Joshi, Bhalchandra V.,Kovac, Pavol,Hajduch, Jan,Kirk, Kenneth L.,Harden, T. Kendall,Jacobson, Kenneth A.
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experimental part
p. 5298 - 5311
(2009/12/04)
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- d-Glucose- and d-mannose-based antimetabolites. Part 2. Facile synthesis of 2-deoxy-2-halo-d-glucoses and -d-mannoses
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Modified d-glucose and d-mannose analogs are potentially clinically useful metabolic inhibitors. Biological evaluation of 2-deoxy-2-halo analogs has been impaired by limited availability and lack of efficient methods for their preparation. We have develop
- Fokt, Izabela,Szymanski, Slawomir,Skora, Stanislaw,Cybulski, Marcin,Madden, Timothy,Priebe, Waldemar
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experimental part
p. 1464 - 1473
(2009/12/09)
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- Microfluidic Chemical Reaction Circuits
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New microfluidic devices, useful for carrying out chemical reactions, are provided. The devices are adapted for on-chip solvent exchange, chemical processes requiring multiple chemical reactions, and rapid concentration of reagents.
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Page/Page column 25; 26-27; 29; 30
(2008/12/08)
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- Studies on the reaction of D-glucal and its derivatives with 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]Octane salts
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The reaction of D-glucal and its derivatives with the electrophilic N-F-fluorination reagents F-TEDA tetrafluoroborate and triflate was studied by means of 19F NMR spectroscopy. In all cases mixtures of 2-deoxy-2-fluoro-D-gluco- and -D-mannopyranose derivatives were formed, the ratio of which was dependent on the nature of the O-protecting groups. Concerning the products arising from the direct addition of reagents across the double bond, the D-gluco-configured compounds (13-20) generally showed higher hydrolysis rates than their D-manno-counterparts (21-28). Product separation was only achieved when single anomers (e.g., 2,4-dinitrophenyl glycosides 29e/37e and disaccharidic fluorides 35d/43d) or per-O-acetates (e.g. 29f/37f) were formed.
- Ortner,Albert,Weber,Dax
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p. 297 - 316
(2007/10/03)
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- A new method for the synthesis of fluoro-carbohydrates and glycosides using selectfluor
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This paper describes a high-yield, one-step synthesis of 2-deoxy-2-fluoro sugars and their glycosides from glycals using the available electrophilic fluorination reagent 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2] octane bis(tetrafluoroborate) (Sel
- Burkart, Michael D.,Zhang, Zhiyuan,Hung, Shang-Cheng,Wong, Chi-Huey
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p. 11743 - 11746
(2007/10/03)
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- A chemoenzymatic synthesis of UDP-(2-deoxy-2-fluoro)-galactose and evaluation of its interaction with galactosyltransferase
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Uridine 5'-diphospho-(2-deoxy-2-fluoro)galactose (UDP-2FGal), prepared and characterized for the first time by a chemoenzymatic method, was found to be a competitive inhibitor of β-1,4-galactosyltransferase with a K(i) value of 149 μM. This study supports that the glycosyltransferase reaction mechanism proceeds through a glycosidic cleavage transition state with sp2 character developed at the anomeric center.
- Hayashi, Takashi,Murray, Brion W.,Wang, Ruo,Wong, Chi-Huey
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p. 497 - 500
(2007/10/03)
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- Chemoenzymatic synthesis of fluorinated carbohydrates: 2-deoxy-2-fluoro-D-glucose and 5-deoxy-5-fluoro-manno-γ-lactol
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Two fluorinated hexoses were prepared from optically active cis-diols 1, which were obtained by microbial oxidation of the corresponding halobenzenes with E. coli JM109 (pDTG 601). The stereochemistry of the products was controlled by careful introduction of fluorine onto the periphery of the cis-diols via opening of epoxides with tetrabutylphosphoniumfluoride dihydrofluoride (TBPF-DF). Oxidative cleavage of the cyclohexene skeleton followed by reductive cyclization led to the fluorinated hexoses.
- Yan, Fengyang,Nguyen, Ba V.,York, Chentao,Hudlicky, Tomas
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p. 11541 - 11548
(2007/10/03)
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- Synthesis of fluorinated analogues of lipid A
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In order to study structure-activity relationships of lipid A derivatives, a series of fluorinated analogues of lipid X was synthesized. Subsequently, these were converted enzymatically into the corresponding disccaharidic lipid A analogues using lipid A
- Vyplel, Hermann,Scholz, Dieter,Loibner, Hans,Kern, Michael,Bednarik, Karl,Schaller, Hans
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p. 1261 - 1264
(2007/10/02)
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- FACTORS AFFECTING THE PURITY OF 2-DEOXY-2-FLUORO-D-GLUCOSE SYNTHESIZED FROM THE REACTIONS OF GLYCALS WITH ACETHYL HYPOFLUORITE
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The reactions of gaseous acethyl hypofluorite with glycals (1a-d) followed by hydrolysis with 2N HCl give 2-deoxy-2-fluoro-D-glucose (2) and 2-deoxy-2-fluoro-D-mannose (3).The ratio of 2 to 3 depends largely on the polarity of the solvent rather than on the size of the substituents on the hydroxyl groups of glucal.The amount of 3 in the final product from the reaction of 1b-d with acethyl hypofluorite ranges from 4percent in non-polar solvents (Freon-11, CCl4, hexane) to ca. 20percent in polar solvents (HOAC, MeOH, DMF, acetone).
- Shiue, Chyhg-Yann,Wolf, A. P.
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p. 255 - 264
(2007/10/02)
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- SYNTHESIS OF 2-DEOXY-2-FLUOROHEXOSES BY FLUORINATION OF GLYCALS IN AQUEOUS MEDIA
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1,5-Anhydro-2-deoxy-D-arabino- (D-glucal), 1,5-anhydro-2-deoxy-D-lyxo- (D-galactal), and 3,4,6-tri-O-acetyl-1,5-anhydro-2-deoxy-D-lyxo-hex-1-enitol (3,4,6-tri-O-acetyl-D-galactal) (3) were fluorinated in water and organic solvent-water with molecular fluorine and, for 18F-labelled compounds, with 18F>fluorine.Chemical yields of 40 and 10percent were obtained for 2-deoxy-2-fluoro-D-glucose and 2-deoxy-2-fluoro-D-mannose, respectively, and 35 and 5percent for 2-deoxy-2-fluoro-D-galactose (12) and 2-deoxy-2-fluoro-D-talose (13), respectively.In the fluorination of 3, the chemical yields of 12 and 13 were 38 and 6percent, respectively.An l.c. separationof 2-deoxy-2-fluoro-D-hexoses is described.
- Diksic, Mirko,Jolly, Dean
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- ACID-CATALYZED EPIMERIZATION OF 2-DEOXY-2-FLUORO-D-HEXOSE
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Interconversion of 2-deoxy-2-fluoro-D-glucose (FDG) and 2-deoxy-2-fluoro-D-mannose (FDM) catalyzed by acid has been detected by 19F-NMR method.Although FDG and FDM were stable towards 1 N hydrochloric acid, in stronger acid media the two hexoses underwent epimerization at C-2.KEYWORDS - epimerization; acid-catalysis; 2-deoxy-2-fluoro-D-glucose; 2-deoxy-2-fluoro-D-mannose; 19F-NMR
- Haradahira, Terushi,Maeda, Minoru,Kanazawa, Yoko,Momozono, Yuko,Kojima, Masaharu
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p. 1407 - 1410
(2007/10/02)
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- Facile, Temperature-Dependent Formation of Gaseous C1 and C2 Perfluoroalkyl Hypofluorites. Applications as Electrophilic Fluorinating Agents.
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A convenient method for continuous-flow production of gaseous C1 and C2 fluoroxyperfluoroalkanes (RfOF) was developed.Passage of 10percent F2 through short columns of CF3CO2Na resulted in the formation of the following hypofluorites: CF3CF2OF, CF3OF, CF3CF(OF)2, and CF2(OF)2.No other significant oxidizing side products or residual F2 were present in the column effluent under normal conditions.Identifications of the hypofluorites were made through direct 19F NMR measurements at -40 deg C of the -196 deg C condensate of the column effluent and also on the basis of stilbene trapping experiments.Hypofluorites were formed rapidly at temperatures at least as low as -110 deg C but no reaction occurred at -160 deg C.The ratios of hypofluorites formed strongly depended on the temperature of the salt column.Yields of CF3CF(OF)2 exceeding 90percent, based on input F2, were obtained at salt temperatures between -110 and -78 deg C.At moderate temperatures (-20 to +20 deg C) CF3CF2OF was the predominant products, accompanied by significant amounts of CF3OF and CF3CF(OF)2 and traces of CF2(OF)2.CF3OF was the major hypofluorite formed at high (60 to 100 deg C) temperatures.No hypofluorites were detected when the column temperature was above 135 deg C.A minimum of specialized equipment is required to produce hypofluorites by this method.It makes expensive or previously exotic, little-studied fluoroxy compounds readily available for synthetic applications.Fluorinations of anisole, 3,4,6-triacetyl-D-glucal, phenylmercuric acetate, and N,N-dimethylphenylacetamide tert-butyldimethylsilyl enolate were carried out to demonstrate the synthetic utility of RfOF and to compare its chemical reactivity with acetyl hypofluorite, an electrophilic fluorinating agent currently in wide use.RfOF, used as a homogeneous reagent, was comparable in fluorinating ability but was less regio- and stereoselective than acetyl hypofluorite in the cases examined.
- Mulholland, G. Keith,Ehrenkaufer, Richard E.
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p. 1482 - 1489
(2007/10/02)
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- A Rapid, Stereoselective, High Yielding Synthesis of 2-Deoxy-2-fluoro-D-hexopyranoses: Reaction of Glycals with Acetyl Hypofluorite
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1,3,4,6-Tetra-O-acetyl-2-deoxy-2-fluoro-α-D-glucopyranose (4) and 1,3,4,6-tetra-O-acetyl-2-deoxy-2-fluoro-α-D-galactopyranose (5) have been synthesized in 78percent and 84percent yields respectively in 5 min by the reaction of acetyl hypofluorite with the corresponding tri-O-acetylglycal (2,3) at -78 deg C.
- Adam, Michael J.
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p. 730 - 731
(2007/10/02)
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