6730-43-4Relevant articles and documents
Oxidative Deamination of N-Acetyl Neuraminic Acid: Substituent Effects and Mechanism
Buda, Szymon,Crich, David
, p. 1084 - 1092 (2016)
A study of the mechanism of the oxidative deamination of the N-nitroso-N-acetyl sialyl glycosides leading with overall retention of configuration to the corresponding 2-keto-3-deoxy-d-glycero-d-galacto-nonulopyranosidonic acid (KDN) glycosides is described, making use of a series of differentially O-protected N-nitroso-N-acetyl sialyl glycosides and of isotopic labeling studies. No evidence is found for stereodirecting participation by ester groups at the 4- and 7-positions. Comparisons are drawn with oxidative deamination reactions of 4-amino-4-deoxy and 2-amino-2-deoxy hexopyranosides and a common mechanism is formulated involving the intermediacy of 1-oxabicyclo[3.1.0]hexyl oxonium ions following participation by the pyranoside ring oxygen. A minor reaction pathway has been uncovered by labeling studies in the β-thiosialosides that results in the exchange of the 4-O-acetyl group by the glacial acetic acid that serves as external nucleophile in the general oxidative deamination process. A mechanism is proposed for this exchange involving participation by the thioglycoside at the level of an intermediate diazoalkane.
Synthesis of C-9 oxidised N-acetylneuraminic acid derivatives as biological probes
Kiefel, Milton J.,Chopra, Pradeep,Madge, Paul D.,Szyczew, Alex,Thomson, Robin J.,Grice, I. Darren,Von Itzstein, Mark
, p. 98 - 100 (2011)
Sialic acids are 9-carbon acidic sugars involved in a number of important biological processes and human diseases. As part of our ongoing interest in the development of novel sialic acids as biological probes, we have developed an efficient and simple synthesis of C-9 oxidised sialic acid derivatives. The key oxidative step involves the use of TEMPO under carefully controlled aqueous pH conditions.
13C-labeled N-acetyl-neuraminic acid in aqueous solution: Detection and quantification of acyclic keto, keto hydrate, and enol forms by 13C NMR spectroscopy
Klepach, Thomas,Carmichael, Ian,Serianni, Anthony S.
, p. 11892 - 11900 (2008)
Aqueous solutions of N-acetyl-neuraminic acid (Neu5Ac, 1) labeled with 13C at C1, C2, and/or C3 were analyzed by 13C NMR spectroscopy to detect and quantitfy the acyclic forms (keto, keto hydrate, enol) present at varying pHs. In addition to pyranoses, solutions contained the keto form, based on the detection of C2 signals at ～198 ppm (～0.7% at pH 2). Spectra of [2-13C] and [3-13C] isotopomers contained signals arising from labeled carbons at ～143 and ～120 ppm, respectively, which were attributed to enol forms. Solution studies of [1,2,3- 13C3]I substantiated the presence of enol (～0.5% at pH 2). Enol was not detected at pH > 6.0. A C2 signal observed at ～94 ppm was identified as C2 of the keto hydrate (～1.9% at pH 2), based partly on its abundance as a function of solution pH. Density functional theory (DFT) calculations were used to study the effect of enol and hydrate structure on JCH and JCC values involving C2 and C3 of these forms. Solvated DFT calculations showed that 2JC2,H3 in cis and trans enols have similar magnitudes but opposite signs, making this J-coupling potentially useful to distinguish enol configurations. Solvent deuterium exchange studies of 1 showed rapid incorporation of 2H from 2H2O at H3axial in the pyranoses at p 2H 8.0, followed by slower exchange at H3equatorial. The acyclic keto form, which presumably participates in this reaction, must assume a pseudo-cyclic conformation in solution in order to account for the exchange selectivity. Weak 13C signals arising from labeled species were also observed consistently and reproducibly in aqueous solutions of 13C-labeled 1, possibly arising from products of lactonization or intermolecular esterification.
Novel method for synthesizing 4, 7-dimethoxy-N-acetylneuraminic acid-fluorescein and its intermediate
-
Paragraph 0036-0037, (2018/05/07)
The invention discloses a novel method for synthesizing 4, 7-dimethoxy-N-acetylneuraminic acid-fluorescein. The method comprises that the 4, 7-dimethoxy-N-acetylneuraminic acid-fluorescein is synthesized from 2-cyano-6-hydroxybenzothiazole as a raw material. The method improves a yield to 60-70% and has the compound production capacity to the gram level. Compared with the existing method, the novel method greatly improves a yield, is free of expensive fluorescein raw materials and greatly reduces a production cost.
Tuning mechanism-based inactivators of neuraminidases: Mechanistic and structural insights
Buchini, Sabrina,Gallat, Francois-Xavier,Greig, Ian R.,Kim, Jin-Hyo,Wakatsuki, Soichi,Chavas, Leonard M. G.,Withers, Stephen G.
supporting information, p. 3382 - 3386 (2014/04/03)
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.
