- Functionalization of 2-Deoxy-2,3-dehydro-N-acetylneuraminic Acid Methyl Ester
-
The acetyl protected 2-deoxy-2,3-dehydroneuraminic acid methyl ester was functionalized by modifying its 2,3-double bond to convert it into new glycosyl donors such as 2,3-dibromo-, 2,3-epoxy-, and 2-halo-3-hydroxyneuraminic acid derivatives.
- Okamoto, Kaoru,Kondo, Tadao,Goto, Toshio
-
-
Read Online
- Selective synthesis of Neu5Ac2en and its oxazoline derivative using BF3·Et2O
-
Application of the Lewis acid BF3·Et2O to the selective synthesis of 5-acetamido-2,6-anhydro-3,5-dideoxy-d-glycero-d-galacto-non-2-enonic acid (Neu5Ac2en) and the related oxazoline, methyl 7,8,9-tri-O-acetyl-2,3,4,5-tetradeoxy-2,3-didehydro-2,3-trideoxy-4′,5′-dihydro-2′-methyloxazolo[5,4-d]- d-glycero-d-talo-non-2-enonate is described.
- Morais, Goreti Ribeiro,Oliveira, Rudi Santiago,Falconer, Robert A.
-
-
Read Online
- A facile synthesis of N-acetylneuraminic acid glycal
-
Treatment of the readily available peracetylated N-acetylneuraminic acid glycosyl chloride [methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-2-chloro-2,3,5- trideoxy-β-D-glycero-D-galactononulopyranosonate)] with anhydrous Na 2HPO4 in refluxing MeCN quantitatively affords the peracetylated N-acetylneuraminic acid glycal [methyl 5-acetamido-4,7,8,9-tetra- O-acetyl-3,5-dideoxy-2,6-anhydro-D-glycero-D-galacto-non-2-enonate], which can be isolated from the reaction mixture by simple filtration and subsequent evaporation of the solvent. No glycal formation was detected at room temperature even after prolonged treatment with Na2HPO4. The method proposed is experimentally simple and allows ready preparation of substantial amounts of the title compound, which is an important intermediate in sialic acid chemistry. Georg Thieme Verlag Stuttgart.
- Kulikova, Nadezhda Yu.,Shpirt, Anna M.,Kononov, Leonid O.
-
-
Read Online
- A facile synthesis of 2-deoxy-2,3-didehydroneuraminic acid derivatives
-
The 2-thio- or 2-selenoglycosides of N-acetylneuraminic acid methyl ester were transformed by successive treatment with dimethyl(methylthio)sulfonium triflate (DMTST) and 1,8-diazabicyclo[5.4.0]-7- undecene (DBU) to give the corresponding methyl 2-deoxy-2,3- didehydroneuraminates in excellent yields. Their acids and their analogues are sialidase inhibitors of pharmaceutical interest.
- Ikeda, Kiyoshi,Konishi, Koji,Sano, Kimihiko,Tanaka, Kiyoshi
-
-
Read Online
- Chemoenzymatic synthesis of sialylated oligosaccharides for their evaluation in a polysialyltransferase assay
-
A series of sialylated β-D-Gal-(1→3)-α-D-GalNAc-octyl containing oligosaccharides representative of those found on mucin type complex O-glycans were synthesized by a chemoenzymatic approach for use in the kinetic characterization of recently cloned polysialyltransferases. Enzymatic incorporation of N-acetylneuraminic acid (sialic acid) into the synthetic acceptors was accomplished by 2,3-(N) and (O)-sialyltransferases to give the target compounds 6-10 in a practical yield.
- Sengupta, Prabal,Misra, Anup Kumar,Suzuki, Misa,Fukuda, Minoru,Hindsgaul, Ole
-
-
Read Online
- Efficient method for the preparation of peracetylated Neu5Ac2en by flash vacuum pyrolysis
-
Peracetylated Neu5Ac2en methyl ester, an intermediate in the synthesis of the influenza neuraminidase inhibitor Relenza, has been synthesized in high yields from peracetylated Neu5Ac methyl ester by flash vacuum pyrolysis. Mechanistic evidence including deuterium labeled studies and DFT (B3LYP) calculations suggest this transformation proceeds via an intramolecular syn-elimination.
- Horn, Evan J.,Gervay-Hague, Jacquelyn
-
-
Read Online
- Donor-Reactivity-Controlled Sialylation Reactions
-
Although tremendous efforts have been made for the efficient preparation of sialosides, controlling the stereochemical outcome of sialylation reaction still remains one of the most challenging tasks due to the unique chemical structure of sialic acid. We developed a new strategy to statistically analyze the stereoselectivity of sialylation reactions on six types of p-tolyl thiosialosides in NIS/TfOH system using Relative Reactivity Value (RRV) as the indicator. Analysis of the reaction mechanism showed the formation of the relatively stable glycosyl bromide and glycosyl chloride intermediates from halide- and triflate-containing promotors in the absence of an acceptor. We found that the α/β-stereoselectivity, yields, and intermediate changes were associated with their donor reactivity. These findings enable to tailor the most suitable building blocks for stereo-controlled sialylation reactions.
- Asressu, Kesatebrhan Haile,Chang, Chun-Wei,Lam, Sarah,Wang, Cheng-Chung
-
p. 4525 - 4530
(2021/08/09)
-
- Facile anomer-oriented syntheses of 4-methylumbelliferyl sialic acid glycosides
-
As part of a program to find new sialidases and determine their enzymatic specificity and catalytic activity, a library of 4-methylumbelliferyl sialic acid glycosides derivatised at the C-5 position were prepared fromN-acetylneuraminic acid. Both α- and β-4-methylumbelliferyl sialic acid glycosides were prepared in high yields and stereoselectivity. α-Anomers were accessedviareagent control by utilising additive CH3CN and TBAI, whereas the β-anomers were synthesised through a diastereoselective addition reaction of iodine and the aglycone to the corresponding glycal followed by reduction of the resulting 3-iodo compounds. Both anomer-oriented synthetic pathways allow for gram-scale stereoselective syntheses of the desired C-5 modified neuraminic acid derivatives for use as tools to quantify the enzymatic activity and substrate specificity of known sialidases, and potential detection and investigation of novel sialidases.
- Hassan, Abdullah A.,Oscarson, Stefan
-
p. 6644 - 6649
(2021/08/10)
-
- Synthesis of the sialylated pentasaccharide repeating unit of the capsular polysaccharide of Streptococcus group B type VI
-
An efficient synthetic strategy has been developed for the synthesis of the sialic acid containing pentasaccharide repeating unit of the cell wall O-antigen of Streptococcus group B type VI strain involving stereoselective α-glycosylation of sialic acid thioglycoside derivative. Stereoselective glycosylation of glycosyl trichloroacetimidate derivatives and thioglycosides were carried out using perchloric acid supported over silica (HClO4–SiO2) as a solid acid catalyst. A panel of sialic acid donors has been screened for achieving satisfactory yield and stereochemical outcome of the glycosylation reaction.
- Manna, Tapasi,Misra, Anup Kumar
-
-
- One pot synthesis of thio -glycosides via aziridine opening reactions
-
A one-pot aziridine opening reaction by glycosyl thiols generated in situ from the corresponding anomeric thio-acetates affords thio-glycosides with a pseudo-disaccharide structure and an N-linked tether. The scope of the one-pot aziridine opening reaction was explored on a series of mono- and disaccharides, creating a class of pseudo-glycosidic compounds with potential for further functionalization. Unexpected anomerization of glycosyl thiols was observed under the reaction conditions and the influence of temperature, base and solvent on the isomerization was investigated. Single isomers were obtained in good to acceptable yields for mannose, rhamnose and sialic acid derivatives. The class of thio-glycomimetics synthesized can potentially be recognized by various lectins, while presenting hydrolytic and enzymatic stability. The nitrogen functionality incorporated in the glycomimetics can be exploited for further functionalization, including tethering to linkers, scaffolds or peptide residues.
- Hribernik, Nives,Tamburrini, Alice,Falletta, Ermelinda,Bernardi, Anna
-
supporting information
p. 233 - 247
(2021/01/14)
-
- A General Method for the Divergent Synthesis of C-9 Functionalised Sialic Acid Derivatives
-
Sialic acids, a ubiquitous family of sugars shown to be involved in numerous biologically important processes, exhibit remarkable structural diversity in nature. Access to these derivatives by chemical and enzymatic means is a major bottle neck in understanding the role played by each particular modification. As part of a program to study such roles and determine the substrate specificity of novel sialic acid aldolases, a general and robust synthetic protocol was devised to gain access to all naturally occurring C-9 functionalised N-acetylneuraminic acid derivatives including esters. These derivatives were synthesised in 11 linear steps from a common advanced intermediate, which allowed for divergent modification at the C-9 position. Four substitutions were installed in this study: O-acetyl, O-lactyl, O-SO3, O-PO3. This synthetic pathway includes both an effective way to benzylate neuraminic acid derivatives, as well as a working methodology towards unnatural β-linked neuraminic acid glycosides.
- Hassan, Abdullah A.,Oscarson, Stefan
-
p. 6102 - 6108
(2020/10/02)
-
- SIALIDASE-RESISTANT SACCHARIDE AND METHOD OF MAKING AND USING THE SAME
-
Disclosed are a method of preparing a saccharide that contains a 3-fluoro-sialic acid and a method of bonding it to a homogeneous antibody. Also within the scope of this invention are compounds each containing a 3-fluoro-sialic acid, monoclonal antibodies bonded to α2,6-linked 3-fluoro-sialoside terminated N-glycans, and treatment of cancer with such monoclonal antibodies.
- -
-
Page/Page column 13; 28-29
(2020/10/20)
-
- A glycal-based photoaffinity probe that enriches sialic acid binding proteins
-
To identify sialic acid binding proteins from complex proteomes, three photocrosslinking affinity-based probes were constructed using Neu5Ac (5 and 6) and Neu5Ac2en (7) scaffolds. Kinetic inhibition assays and Western blotting revealed the Neu5Ac2en-based 7 to be an effective probe for the labeling of a purified gut microbial sialidase (BDI_2946) and a purified human sialic acid binding protein (hCD33). Additionally, LC–MS/MS affinity-based protein profiling verified the ability of 7 to enrich a low-abundance sialic acid binding protein (complement factor H) from human serum thus validating the utility of this probe in a complex context.
- Thuy-Boun, Peter S.,Wolan, Dennis W.
-
supporting information
p. 2609 - 2612
(2019/08/07)
-
- NEW POTENT SIALYLTRANSFERASE INHIBITORS
-
The present invention relates to anew class of sialyltransferase inhibitors. The class features a carbamate or similar moiety on the amine of a neuraminic acid derivative. Such inhibitors are suitable for use as a medicament, for example for treating, preventing, or delaying bacterial infection, viral infection, cancer, a disorder of sialic acid metabolism, or an autoimmune disease.
- -
-
-
- Selective Inhibition of Sialic Acid-Based Molecular Mimicry in Haemophilus influenzae Abrogates Serum Resistance
-
Pathogens such as non-typeable Haemophilus influenzae (NTHi) evade the immune system by presenting host-derived sialic acids. NTHi cannot synthesize sialic acids and therefore needs to utilize sialic acids originating from host tissue. Here we report sialic acid-based probes to visualize and inhibit the transfer of host sialic acids to NTHi. Inhibition of sialic acid utilization by NTHi enhanced serum-mediated killing. Furthermore, in an in vitro model of the human respiratory tract, we demonstrate efficient inhibition of sialic acid transfer from primary human bronchial epithelial cells to NTHi using bioorthogonal chemistry. Molecular mimicry of non-typeable Haemophilus influenzae (NTHi) with host sialic acid sugars mediates resistance to serum killing and increases virulence. Heise et al. have developed sialic acid derivatives that allow either visualization or inhibition of host sialic acid transfer to NTHi, the latter enhancing serum-mediated killing.
- Heise, Torben,Langereis, Jeroen D.,Rossing, Emiel,de Jonge, Marien I.,Adema, Gosse J.,Büll, Christian,Boltje, Thomas J.
-
p. 1279 - 8,1285
(2018/06/14)
-
- Stereocontrolled Synthesis of Phenolic α-d-Glycopyranosides
-
Adopting the ‘remote activation concept’ toward stereocontrolled glycoside synthesis with minimal use of protection groups, a general synthesis of phenolic 1,2-cis glycopyranosides is reported, as exemplified by aryl α-d-galacto-, α-d-gluco- and 2-azido α-d-glucopyranosides among others using glycosyl donors bearing an anomeric (3-bromo-2-pyridyloxy) group and catalyzed by methyl triflate.
- St-Pierre, Gabrielle,Dafik, Laila,Klegraf, Ellen,Hanessian, Stephen
-
supporting information
p. 3575 - 3588
(2016/10/17)
-
- Access to 3-O-Functionalized N-Acetylneuraminic Acid Scaffolds
-
Direct access to 3-O-functionalized 2-α-N-acetylneuraminides and their corresponding 2,3-dehydro-2-deoxy-N-acetylneuraminic acid derivatives is described. Initially, a stereoselective ring-opening of the key intermediate N-acetylneuraminic acid (Neu5Ac) 2,3-β-epoxide with an alcohol provided the 3-hydroxy α-glycoside. O-Alkylation of the C3 hydroxyl group generated novel 3-O-functionalized Neu5Ac derivatives that provided the corresponding unsaturated derivatives upon elimination.
- Pascolutti, Mauro,Madge, Paul D.,Thomson, Robin J.,Von Itzstein, Mark
-
supporting information
p. 7746 - 7751
(2015/08/18)
-
- 2-DEOXY-2,3-DIDEHYDROSIALIC ACID DERIVATIVE AND PRODUCTION METHOD THEREOF
-
PROBLEM TO BE SOLVED: To provide a sialic acid derivative that has structural diversity at a C-1 position and a method of producing the same by a click reaction. SOLUTION: This invention provides a 2-deoxy-2,3-didehydrosialic acid derivative represented by formula [1] (R1 is thio carboxyl group, thioamide group, acylsulfonamide group or sulfonyl amidine group). COPYRIGHT: (C)2015,JPOandINPIT
- -
-
-
- Tuning mechanism-based inactivators of neuraminidases: Mechanistic and structural insights
-
3-Fluorosialosyl fluorides are inhibitors of sialidases that function by the formation of a long-lived covalent active-site adduct and have potential as therapeutics if made specific for the pathogen sialidase. Surprisingly, human Neu2 and the Trypanosoma cruzi trans-sialidase are inactivated more rapidly by the reagent with an equatorial fluorine at C3 than by its axial epimer, with reactivation following the same pattern. To explore a possible stereoelectronic basis for this, rate constants for spontaneous hydrolysis of the full series of four 3-fluorosialosyl fluorides were measured, and ground-state energies for each computed. The alpha (equatorial) anomeric fluorides hydrolyze more rapidly than their beta anomers, consistent with their higher ground-state energies. However ground-state energies do not explain the relative spontaneous reactivities of the 3-fluoro-epimers. The three-dimensional structures of the two 3-fluoro-sialosyl enzyme intermediates of human Neu2 were solved, revealing key stabilizing interactions between Arg21 and the equatorial, but not the axial, fluorine. Because of changes in geometry these interactions will increase at the transition state, likely explaining the difference in reaction rates. Understanding reactivity and selectivity: The mechanistic basis for the surprisingly different rates of inactivation and reactivation of human and Trypanosoma cruzi sialidases by the two 3-fluoro epimers of 2,3-difluorosialic acid was probed through spontaneous hydrolysis kinetics, computational analysis, and X-ray crystallography.
- Buchini, Sabrina,Gallat, Francois-Xavier,Greig, Ian R.,Kim, Jin-Hyo,Wakatsuki, Soichi,Chavas, Leonard M. G.,Withers, Stephen G.
-
p. 3382 - 3386
(2014/04/03)
-
- Synthesis and elimination of C-3-labeled thiosialosides
-
The synthesis of C-3-labeled phenylthio sialic acid derivatives and an investigation of stereoselectivity in elimination reactions for the synthesis of 2,3-dehydro derivatives (glycals) is described. The experimental results are consistent with the existence of a conformational change and may be indicative of the intermediacy of an all-axial oxacarbenium ion.
- De Meo, Cristina,Wallace, Clare E.,Geringer, Scott A.
-
p. 2676 - 2679
(2014/06/09)
-
- Probing the influence of protecting groups on the anomeric equilibrium in sialic acid glycosides with the persistent radical effect
-
A method for the investigation of the influence of protecting groups on the anomeric equilibrium in the sialic acid glycosides has been developed on the basis of the equilibration of O-sialyl hydroxylamines by reversible homolytic scission of the glycosidic bond following the dictates of the Fischer-Ingold persistent radical effect. It is found that a trans-fused 4O,5N-oxazolidinone group stabilizes the equatorial glycoside, i.e., reduces the anomeric effect, when compared to the 4O,5N-diacetyl protected systems. This effect is discussed in terms of the powerful electron-withdrawing nature of the oxazolidinone system, which in turn is a function of its strong dipole moment in the mean plane of the pyranose ring system. The new equilibration method displays a small solvent effect and is most pronounced in less polar media consistent with the anomeric effect in general. The unusual (for anomeric radicals) poor kinetic selectivity of anomeric sialyl radicals is discussed in terms of the planar π-type structure of these radicals and of competing 1,3-diaxial interactions in the diastereomeric transition states for trapping on the α- and β-faces of the radical.
- Kancharla, Pavan K.,Kato, Takayuki,Crich, David
-
supporting information
p. 5472 - 5480
(2014/05/06)
-
- An efficient synthesis of C3 C-alkylated Neu5Ac2en derivatives
-
C3-modified Neu5Ac2en derivatives can be used to study the flexible 150-loop region of influenza virus sialidases and also provide a new template for the development of next-generation sialidase inhibitors. This Letter describes an efficient synthetic route towards the large scale synthesis of C3 C-alkylated Neu5Ac2en derivatives. The key intermediate, a 3-eq-allyl-Neu5Ac derivative, is formed by stereoselective addition of the allyl group in an equatorial configuration at C3, regardless of the stereochemistry of the bromohydrin precursor.
- Rudrawar, Santosh,Pascolutti, Mauro,Bhatt, Beenu,Thomson, Robin J.,Von Itzstein, Mark
-
supporting information
p. 1198 - 1201
(2013/03/14)
-
- Dissecting the Influence of Oxazolidinones and Cyclic Carbonates in Sialic Acid Chemistry
-
At a moment's notice: Thermal equilibration of 1 and mass spectral analysis of sialyl phosphates suggest that the 4O,5N-oxazolidinone and the 4,5-O-carbonate systems influence the anomeric effect and the mechanisms of sialidation by virtue of their dipole moment in the mean plane of the pyranose ring. The electron-withdrawing effect destabilizes 2 and promotes associative glycosylation mechanisms. TEMPO=2,2,6,6-tetramethylpiperidine N-oxide. Copyright
- Kancharla, Pavan K.,Navuluri, Chandrasekhar,Crich, David
-
supporting information
p. 11105 - 11109
(2013/01/15)
-
- Studies on the sialylation of galactoses with different C-5 modified sialyl donors
-
Synthetic sialylated glycans provide useful tools to study carbohydrate-mediated biological recognition; however chemical sialylation is the most challenging practice in preparative carbohydrate chemistry, which is often associated with low yields and poor stereoselectivity. Herein, we conducted extensive studies on sialylation with five types of 5-N-modified sialyl donors and four types of galactosyl acceptors. Our studies have shown that a good combination between the donor and the acceptor seems necessary to achieve high yield and stereoselectivity. None of the donors or acceptors showed 'universal' utility toward the sialylation reaction.
- Gong, Jianzhi,Liu, Han,Li, Xuechen,Nicholls, John M.
-
p. 91 - 99,9
(2012/12/13)
-
- Concentration dependence of glycosylation outcome: A clue to reproducibility and understanding the reasons behind
-
Changes in the concentration of reagents (0.009-0.2 M) have been shown to dramatically effect the yield and stereoselectivity of glycosylation with a sialic acid based glycosyl donor in a complex nonlinear manner that correlates with changes in the structures of the supramers of the reagents. The yield of disaccharide gradually increases with concentration and levels off at concentrations of glycosyl donor higher than 69 mM. The ratio of anomers is very high at some concentrations (α/β ≈ 20:1), moderate (α/β ≈ 8:1) or very low (α/β ≈ 4:1) at others. The formation of mixed supramers of glycosyl donor and glycosyl acceptor at concentrations exceeding 69 mM was detected by polarimetry and laser light scattering. Depending on the concentration, the reagents can form different supramers with distinct chemical properties. The changes in supramer structure (indicated by the red vertical arrows) correlate with the glycosylation yield (1) and stereoselectivity (2) and can be detected by physical methods. Copyright
- Kononov, Leonid O.,Malysheva, Nelly N.,Orlova, Anna V.,Zinin, Alexander I.,Laptinskaya, Tatiana V.,Kononova, Elena G.,Kolotyrkina, Natalya G.
-
scheme or table
p. 1926 - 1934
(2012/05/31)
-
- Reinvestigation of the C5-acetamide sialic acid donor for α-selective sialylation: Practical procedure under microfluidic conditions
-
Despite the previous literature describing the "low-to-modest" efficiency, the readily available C5-acetamide donor was reinvestigated for its use in α-sialylation under microfluidic conditions. The N-phenyltrifluoroacetimidate donor was efficiently mixed with an appropriate amount of TMSOTf to produce the α(2-6) and α(2-3)-sialylation products of galactose and glucosamine acceptors in excellent yields and with nearly perfect α-selectivity.
- Uchinashi, Yosuke,Nagasaki, Masahiro,Zhou, Jiazhou,Tanaka, Katsunori,Fukase, Koichi
-
scheme or table
p. 7243 - 7248
(2011/10/31)
-
- Syntheses of 2-deoxy-2,3-didehydro-N-acetylneuraminic acid analogues modified by N-sulfonylamidino groups at the C-4 position and biological evaluation as inhibitors of human parainfluenza virus type 1
-
Eleven novel sialidase inhibitors 9 and 10 with an N-sulfonylamidino group at the C-4 position of Neu5Ac2en 1 against human parainfluenza virus type 1 (hPIV-1) were synthesized using copper-catalyzed three-component coupling reactions, and their inhibitory activities against hPIV-1 sialidase were studied.
- Nishino, Reiko,Ikeda, Kiyoshi,Hayakawa, Takuya,Takahashi, Tadanobu,Suzuki, Takashi,Sato, Masayuki
-
p. 2418 - 2427
(2011/05/12)
-
- N,N-Diacetylsialyl chloride-a novel readily accessible sialyl donor in reactions with neutral and charged nucleophiles in the absence of a promoter
-
N,N-Diacetylneuraminic acid glycosyl chloride was prepared for the first time and made to react with various nucleophiles to give the corresponding α-glycosyl phosphate, β-glycosyl dibenzyl phosphate, α-glycosyl azide, α-phenyl thioglycoside and α-glycosyl xanthate in 65-82% yields and high stereoselectivity while its reactions with simple alcohols were not stereoselective. The new sialyl donor made possible the first stereoselective synthesis of sialic acid glycosyl phosphate with α-configuration and highly efficient synthesis of β-configured sialic acid glycosyl dibenzyl phosphate.
- Orlova, Anna V.,Shpirt, Anna M.,Kulikova, Nadezhda Y.,Kononov, Leonid O.
-
experimental part
p. 721 - 730
(2010/06/14)
-
- Regio- and stereocontrolled palladium-catalyzed allylic substitution on n-acetylneuraminic acid derivatives
-
A process for highly effective regio- and stereoselective palladium-catalyzed allylic substitution of 2,3-unsaturated derivatives of N-acetylneuraminic acid (Neu5Ac2en) has been developed. We show that the efficiency of the allylation reaction depends on suitable protecting groups on the starting material and that, with sodium malonate anion as a nucleophile, the regioselectivity can be fine-tuned by the nature of the ligands associated with the palladium complex. These results are explained by the stoichiometric preparation and study of the highly probable complexes involved in the catalytic reaction. Reactions of this type were also applied to other nucleophiles for the construction of C-C, C-N, and. C-O bonds, leading to the major formation of the C-4 regioisomers. The selective transformation of some of the substitution products provided easy access to a variety of modified sialic acid derivatives that might serve as useful, sialyl building blocks for biological research.
- Chang, Chih-Wei,Norsikian, Stephanie,Guillot, Regis,Beau, Jean-Marie
-
experimental part
p. 2280 - 2294
(2010/07/10)
-
- 6 -SIALYLLACTOSE SALTS AND PROCESS FOR THEIR SYNTHESIS AND FOR THE SYNTHESIS OF OTHER A-SIALYLOLIGOSACCHARIDES
-
The present invention relates to a process of synthesis of α-sialyl oligosaccharides and in particular of 6'-sialyllactose and its salts comprising a step of coupling by Koenigs-Knorr reaction under conditions that allow its use on an industrial scale.
- -
-
Page/Page column 20-21
(2010/11/03)
-
- Useful sialic acid modifications catalyzed by palladium
-
A stereo- and regioselective allylic substitution on simple N-acetylneuraminic acid (Neu5Ac2en) derivatives that ensures the control of the regio- and stereoselectivity and affords the C-2 or C-4 products with high efficiency, was studied. The Neu5Ac2en substrates were easily prepared from the peracetylated methyl ester 9 obtained by standard treatment overnight of the corresponding Neu5Ac methyl ester. Treatment of acetate 10 under Pd0-catalyzed allylic substitution conditions using sodium dimethylmalonate as a nucleophile failed to provide any alkylation product. The regioselectivity was largely improved to a synthetically useful level when using a more basic monophosphine ligand. A complete reversal of the regioselectivity occurred when the reaction was performed in the presence of bidentate phosphine. Selective transformations of these products provide easy entry to a variety of modified sialic acid derivatives, which can serve as useful sialyl building blocks for biological research.
- Chang, Chih-Wei,Norsikian, Stephanie,Beau, Jean-Marie
-
body text
p. 5195 - 5199
(2009/12/22)
-
- Synthesis and structural characterization of sialic acid - Glutamic acidhybrid foldamers as conformational surrogates of α-2,8-linked pol ysialic acid
-
Surface expression of α-(2,8)-linked polymers of sialic acid in adult tissues has been correlated with metastasis of several human cancers. One approach to chemotherapeutic intervention against the spread of these cancers involves the development of immunogenic molecules that elicit an antibody response against α-(2,8)-linked polysialic acids. Naturally occurring polysialic acids are not viable candidates because they are present during embryonic development and are recognized as self bythe immune system. These natural polymers also have poor pharmacokineti c properties because they are readily degraded by neuraminidase enzymes.We have been interested in developing structural surrogates of polysial ic acids in an effort to overcome these limitations. Reported herein aremicrowave-assisted solid-phase peptide syntheses and structural charact erization studies of a series of α/δ hybrid peptides derivedfrom Fmoc-Neu2en and Fmoc-Glu(OtBu)-OH. Conformational experiments incl uding circular dichroism, NH/ ND exchange, and ROESY in aqueous solutionwere performed to study the secondary structures of these hybrid foldam ers. ROESY data were analyzed with the assistance of XPLOR-NIH that was modified to include parameter and topology files to accommodate unnatural amino acids and the δ amide linkages. The results indicate that stable secondary structure is dependent upon both the amino acid sequence and the configuration of Glu. The most stable foldamer was composed ofa total of 6 residues beginning with L-Glu at the carboxy terminus and alternating Neu2en and L-Glu residues. In water, this foldamer adopts a right-handed helical conformation with 3.7 residues per turn, 7.4 ? pitch, 5.8 ? diameter, and a length of 18.5 ?, which is stabiliz ed by both classical C= O···H-N backbone interactions and by pyranose ring O and L-Glu HN H-bonding. These structural features orient the L-Glu carboxylates along the helical backbone with a periodicity that matches the carboxylate positions along the reported G2+ left-handed helix of α-(2,8)-polysialic acid. However, the charge density of the foldamer is one-half that of the natural polymer. These findings provide a fundamental understanding of the factors thatinfluence stable secondary structure in hybrid Neu2en/Glu systems, and the tools we have developed establish a viable platform for the rational design of α-(2,8)-polysialic acid surrogates.
- Saludes, Jonel P.,Ames, James B.,Gervay-Hague, Jacquelyn
-
supporting information; scheme or table
p. 5495 - 5505
(2009/09/25)
-
- Systematic syntheses of influenza neuraminidase inhibitors: A series of carbosilane dendrimers uniformly functionalized with thioglycoside-type sialic acid moieties
-
In order to develop novel influenza sialidase inhibitors, we constructed a library of glycoclusters composed of twelve types of sialylated dendrimers with thioglycosidic linkage that are resistant to hydrolysis by the sialidases. These sialodendrimers were synthesized by condensation reaction between a thiosialoside modified on the aglycon terminal end by a thioacetyl group and twelve types of carbosilane dendrimers having brominated terminal ends under deacetylation conditions, and temporal re-protection was performed for purification. Removal of all protection of the glycodendrimers was accomplished by transesterification and subsequent saponification to provide corresponding water-soluble glycodendrimers in good yields. For investigation of the structure-activity relationship, dendrimer scaffolds having differences in number of the sugar moieties, such as 3-, 4-, 6- and 12-functionalized dendrimers, and in linkage patterns, such as normal aliphatic linkage, ether- and amide-linkages. Biological evaluations of these glycodendrimers showed that all of the ether- and amide-elongated compounds had inhibitory potencies for the influenza sialidases in the mM range, while compounds having normal aliphatic linkage did not have any activities except for a 12-functionalized compound.
- Sakamoto, Jun-Ichi,Koyama, Tetsuo,Miyamoto, Daisei,Yingsakmongkon, Sangchai,Hidari, Kazuya I.P.J.,Jampangern, Wipawee,Suzuki, Takashi,Suzuki, Yasuo,Esumi, Yasuaki,Nakamura, Takemichi,Hatano, Ken,Terunuma, Daiyo,Matsuoka, Koji
-
scheme or table
p. 5451 - 5464
(2009/12/09)
-
- Phosphite-based sialic acid donors in the synthesis of α(2→9) oligosialic acids
-
The combination of a phosphite donor and an anomeric thiocresol-protected acceptor, both with a TFA protecting group at C-5 of the sialic acid, provides good α-selectivity and yield in sialylation. Although the convergent synthetic strategy of using a phosphite disialo-donor and a disialo-acceptor assembles tetra-sialic acid efficiently, overcoming the low α-selectivity of α-anomer and purifying it remain to be achieved. Furthermore, mono- and di-sialic acids were, respectively, conjugated on carrier protein, keyhole limpet hemocyanin. The enzymatic hydrolysis method is recommended for estimating the amount of sialic acid on a protein conjugate.
- Lin, Chang-Ching,Adak, Avijit Kumar,Horng, Jia-Cherng,Lin, Chun-Cheng
-
scheme or table
p. 4714 - 4725
(2009/10/17)
-
- Investigation into an efficient synthesis of 2,3-dehydro-N-acetyl neuraminic acid leads to three decarboxylated sialic acid dimers
-
Sialic acid, an important carbohydrate found incorporated on the cell surface of many organisms, has been modified for use in a wide range of biological and pharmaceutical applications. We hypothesized that 4,7,8,9-tetra-O-acetyl-2-deoxy-2,3-dehydro-N-acetyl neuraminic acid methyl ester (4) could be efficiently synthesized in a one-pot reaction by heating peracetylated sialic acid (2) in pyridine and acetic anhydride to induce β-elimination. When reduced to practice, this reaction produced only modest yields of 4. Six compounds, including three new decarboxylated sialic acid dimers, were also found to have been synthesized in the reaction. In an effort to better understand the chemistry and the mechanisms of this reaction, all of the side products were isolated and fully characterized.
- Horn, Evan J.,Saludes, Jonel P.,Gervay-Hague, Jacquelyn
-
p. 936 - 940
(2008/09/16)
-
- Use of a recycle-type SEC method as a powerful tool for purification of thiosialoside derivatives
-
An efficient separation between fully acetylated thiosialoside methyl esters and fully acetylated Neu5Ac2en methyl esters was accomplished by means of a size-exclusion chromatography (SEC) method. Purity determinations and structural elucidation of the isolated compounds were performed by a combination of elemental analyses and spectroscopic analyses, including IR, 1H, and 13C NMR, and mass spectroscopic analyses.
- Sakamoto, Jun-Ichi,Takita, Chiharu,Koyama, Tetsuo,Hatano, Ken,Terunuma, Daiyo,Matsuoka, Koji
-
scheme or table
p. 2735 - 2739
(2009/04/11)
-
- Efficient synthesis of a sialic acid α(2→3)galactose building block and its application to the synthesis of ganglioside GM3
-
(Chemical Equation Presented) Glycosylation of various galactose derivatives with O-acetylated sialic acid N-phenyltrifluoroacetimidate as the donor was investigated. Efficient α(2,3)sialylation of galactose, with up to 73% yield and 8.4:1 stereoselectivity, was realized when 2,3,4-unprotected galactose derivatives and TBSOTf were used as acceptors and promoter, respectively. Sialylation of 2-(trimethylsilyl)ethyl 6-O-tert- butyldiphenylsilyl-β-D-galactopyranoside (3f) gave the best result, and the resultant Neu5Ac α(2→3)Gal disaccharide was successfully used in the synthesis of ganglioside GM3.
- Liu, Yunpeng,Ruan, Xiaohong,Li, Xiangpeng,Li, Yingxia
-
p. 4287 - 4290
(2008/09/20)
-
- Synthesis and evaluation of 4-O-alkylated 2-deoxy-2,3-didehydro-N-acetylneuraminic acid derivatives as inhibitors of human parainfluenza virus type-3 sialidase activity
-
The X-ray crystal structure of the paramyxoviral surface glycoprotein haemagglutinin-neuraminidase (HN) from Newcastle Disease virus was used as a template to design inhibitors of the HN from human parainfluenza virus type-3 (hPIV-3). 4-O-Alkylated derivatives of 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en), accessed from 8,9-O-isopropylidenated-Neu5Ac2en1Me, were found to inhibit the sialidase (neuraminidase) activity of hPIV-3 (strain C243) in the range of 3-30 μM. This is comparable or improved activity compared to the parent 4-hydroxy compound.
- Tindal, David J.,Dyason, Jeffrey C.,Thomson, Robin J.,Suzuki, Takashi,Ueyama, Hiroo,Kuwahara, Yohta,Maki, Naoyoshi,Suzuki, Yasuo,Von Itzstein, Mark
-
p. 1655 - 1658
(2007/10/03)
-
- One-pot synthesis of sialo-containing glycosyl amino acids by use of an N-trichloroethoxycarbonyl-β-thiophenyl sialoside
-
We describe an efficient synthesis of 2,6- and 2,3-sialyl T antigens linked to serine in a one-pot glycosylation. We first investigated the glycosidation of thiosialosides by varying the N-protecting group. Modification of the C-5 amino group of β-thiosialosides into the N-9-fluorenylmethoxycarbonyl, N-2,2,2-trichloroethoxycarbonyl (N-Troc), and N-trichloroacetyl derivatives enhanced the reactivity of these compounds towards glycosidation. Addition of a minimum amount of 3 A molecular sieves was also effective in improving the yield of α-linked sialosides. Next, we conducted one-pot syntheses of the glycosyl amino acids by using the N-Troc sialyl donor. The N-Troc derivative can be converted into the N-acetyl derivative without racemization of the amino acids. Branched-type one-pot glycosylation, initiated by regioselective glycosylation of the 3,6-dihydroxy galactoside with the N-Troc-β-thiophenyl sialoside, provided the protected 2,6-sialyl T antigen in good yield. Linear-type one-pot glycosylation, initiated by chemoselective glycosylation of galactosyl fluoride with the N-Troc-β-thiophenyl sialoside, afforded the protected 2,3-sialyl T antigen in excellent yield. Both protected glycosyl amino acids were converted into the fully deprotected 2,6- and 2,3-sialyl T antigens linked to serine in good yields.
- Tanaka, Hiroshi,Adachi, Masaatsu,Takahashi, Takashi
-
p. 849 - 862
(2007/10/03)
-
- N-trifluoroacetyl sialyl phosphite donors for the synthesis of α(2 → 9) oligosialic acids
-
(Chemical Equation Presented) A new method for the synthesis of α(2 → 9) oligosialic acids is developed using phosphite sialyl donors that are protected with a C-5 N-trifluoroacetyl (NHTFA) substituent. Compared with conventional donors, these donors gave a higher degree of α-anomeric selectivity during glycosidic bond formation and better yields during iterative sialylation in the synthesis of oligosialic acids.
- Lin, Chang-Ching,Huang, Kuo-Ting,Lin, Chun-Cheng
-
p. 4169 - 4172
(2007/10/03)
-
- Conversion of N-acetylneuraminic acid glycosyl chloride into dibenzyl glycosyl phosphate: O-glycosylation in the absence of a promoter
-
Readily accessible N-acetylneuraminic acid (Neu5Ac) glycosyl chloride, which was regarded to be a poor glycosyl donor, was shown to react with dibenzyl phosphoric acid salts in the absence of glycosylation promoters to give the corresponding β-Neu5Ac dibenzyl glycosyl phosphate in high yield.
- Shpirt,Kononov,Torgov,Shibaev
-
p. 717 - 719
(2007/10/03)
-
- Synthesis of Oligomers Derived from Amide-Linked Neuraminic Acid Analogues
-
N-Fluoren-9-ylmethoxycarbonyl-protected sugar amino acids derived from α-O-methoxy- and 2,3-dehydroneuraminic acids have been prepared. Incorporation of these monomer units into solid-phase synthesis led to the efficient synthesis of two series of oligomers varying from one to eight units in length. The (1-5)-linked amides of 2,3-dehydroneuraminic acid were further subjected to hydrogenation giving a third series of oligomers with a β-hydrido substituent at the anomeric carbon.
- Gregar, Travis Q.,Gervay-Hague, Jacquelyn
-
p. 1001 - 1009
(2007/10/03)
-
- An effective sialylation method using N-Troc- and N-Fmoc-protected β-thiophenyl sialosides and application to the one-pot two-step synthesis of 2,6-sialyl-T antigen
-
We describe an efficient sialylation method using β-thiosialosides with various N-protecting groups. Modification of the C-5 amino group of β-thiosialosides into N-Fmoc and N-Troc derivatives enhanced their reactivity in glycosidation. In addition, a minimum amount of MS-3 A? was effective to improve the yield of α-linked sialoside. Branched type one-pot glycosylation initiating glycosidation of the N-Troc-protected β-thiophenyl sialoside at a primary alcohol provided the protected 2,6-sialyl-T antigen in good yield, which was converted to the fully deprotected glycosyl amino acid.
- Adachi, Masaatsu,Tanaka, Hiroshi,Takahashi, Takashi
-
p. 609 - 614
(2007/10/03)
-
- Study of interhalogens/silver trifluoromethanesulfonate as promoter systems for high-yielding sialylations
-
We have studied interhalogen/silver trifluoromethanesulfonate (IX/AgOTf) promoted glycosylations and found differences in the sensitivity of the formed oxocarbenium ions (e.g. from compounds with or without participating groups) toward halide nucleophiles. These differences can be explained using the HSAB theory. By applying this theory on sialylations, we increased the yield for a model reaction from a highly unpredictable 35-46% using ICl to 74% using IBr. We have also showed that the most prominent role of the silver ions is lowering the concentration of the halide nucleophile rather than activating the interhalogen compound and, by increasing the amount of AgOTf from 1 to 1.5 equiv (with respect to IBr), the yield in the model reaction improved from 74% to 89%. A comparison of two different anomeric leaving groups showed that glycal formation can be minimized using a thiophenyl donor instead of xanthate. By combining these observations, we were able to increase the yield of the model reaction to 97%.
- Meijer, Andreas,Ellervik, Ulf
-
p. 7407 - 7412
(2007/10/03)
-
- Selective preparation of glycosyl sulfone or glycal by treatment of phenyl thioglycoside of N-acetylneuraminic acid with m-chloroperbenzoic acid
-
Treatment of acetylated phenyl thioglycoside of N-acetylneuraminic acid with m-chloroperbenzoic acid (MCPBA) in CH2Cl2 affords quantitatively mixtures of the respective sulfone and glycal free from the sulfoxide. The outcome of the reaction does not depend on the anomeric configuration of the starting thioglycoside. The sulfone can be selectively prepared (yield ca 100 percent) by oxidation with an excess of MCPBA and NaHCO3. In the presence of pyridine (2 equiv.) and MCPBA (2 equiv.), the major product is glycal (yields 81-88 percent). This version of the reaction can be regarded as a new method for the preparation of sialic acid glycals.
- Kononov, L. O.,Komarova, B. S.,Nifantiev, N. E.
-
p. 698 - 702
(2007/10/03)
-
- Synthesis of novel mimetics of CMP-sialic acid as the inhibitors of sialyltransferases
-
Novel mimetics of CMP-sialic acid were designed as the inhibitors of sialyltransferases. They were synthesized in a short step from a cytosine carrying β-hydroxy-α-L-amino acid based on the knowledge that nikkomycin, a peptidic derivative of an uracil carrying amino acid, shows a potent inhibitory activity toward N-acetyl-D-glucosaminyltransferases that employ UDP-N-acetyl-D-glucosamine as the donor substrate. The cytosine carrying β-hydroxyl-α-L-amino acid, a key intermediate in our synthetic strategy, was easily prepared by the L-threonine aldolase (LTA) catalyzed reaction.
- Tanaka, Toru,Ozawa, Machiko,Miura, Tsuyoshi,Inazu, Toshiyuki,Tsuji, Shuichi,Kajimoto, Tetsuya
-
p. 1487 - 1490
(2007/10/03)
-
- An efficient method for the preparation of 2-hydroxy- and 2-aminoglycals from glycosyl sulfoxides
-
A new and efficient route to 2-hydroxy- and 2-aminoglycals from glycosyl sulfoxides has been developed.
- Liu, Junjie,Huang, Cheng-Yuan,Wong, Chi-Huey
-
p. 3447 - 3448
(2007/10/03)
-
- Phenylboronic acid as a labile protective agent: the selective derivatisation of 1,2,3-triols
-
The ability of phenylboronic acid to act as a labile protective agent for open-chain 1,2,3-triols is demonstrated in the highly selective terminal derivatisation of D-mannitol and an antiviral sialic acid derivative. Protection, derivatisation and deprotection are carried out in a single pot, yielding analytically pure products in moderate yield, without the need for chromatography or formal recrystallisation steps. In both classes of compound, the selectivity of protection is found to be complementary to existing methods, providing access to relatively uncommon 1,6-diesters and the 1,6-bis(benzyl ether) of D-mannitol, and 9-o-acylsialic acid derivatives.
- Bhaskar, Vijaya K.,Duggan, Peter J.,Humphrey, David G.,Krippner, Guy Y.,McCarl, Victoria,Offermann, Daniel A.
-
p. 1098 - 1102
(2007/10/03)
-
- Chemoselective glycosidation strategy based on glycosyl donors and acceptors carrying phosphorus-containing leaving groups: A convergent synthesis of ganglioside GM3
-
A convergent synthesis of ganglioside GM3 has been achieved by capitalizing on three different phosphorus-containing leaving groups, in which the key features involve a chemo- and regioselective α-glycosidation of sialyl phosphite with partially benzylated galactosyl tetramethylphosphorodiamidate by the aid of trifluoromethanesulfonic acid and a traditionally uncommon coupling of an α-sialyl-(2→3)- galactosyl donor with a glucosylceramide building block which has the β-O-linked ceramide prebuilt into the glucose by a diphenyl phosphate method. (C) 2000 Elsevier Science Ltd.
- Sakamoto,Nakamura,Tsuda,Hashimoto
-
p. 7691 - 7695
(2007/10/03)
-
- Thio-oligosaccharides of sialic acid - Synthesis of an α(2→3) sialyl galactoside via a gulofuranose/galactopyranose approach
-
A new approach to the synthesis of thio-oligosaccharides containing the N-acetylneuraminic acid-α(2→3)-galactopyranose linkage is described. 3-O-(Trifluoromethylsulfonyl)gulofuranose derivative 5 can be converted into the α-2,3-sialyl-3-thiogalactofuranose derivative 8 in good yield. Partial deprotection of the thiodisaccharide provides an α/β mixture of both galactofuranose and galactopyranose isomers, but this mixture can be transformed efficiently into the desired pyranose-ring form to allow further elaboration into other glycosides via trichloroacetimidate donor 21. This strategy avoids introducing sulfur into 3-O-(trifluoromethylsulfonyl)gulopyranose derivatives, which can be prone to elimination side reactions.
- Turnbull, W. Bruce,Field, Robert A.
-
p. 1859 - 1866
(2007/10/03)
-
