25875-99-4Relevant academic research and scientific papers
A General Method for the Divergent Synthesis of C-9 Functionalised Sialic Acid Derivatives
Hassan, Abdullah A.,Oscarson, Stefan
, p. 6102 - 6108 (2020)
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.
Synthesis and chemical characterization of several perfluorinated sialic acid glycals and evaluation of their: In vitro antiviral activity against Newcastle disease virus
Rota,Papini,La Rocca,Montefiori,Cirillo,Piccoli,Scurati,Olsen,Allevi,Anastasia
, p. 1505 - 1513 (2017/07/25)
Newcastle Disease Virus (NDV), belonging to the Paramyxoviridae family, causes a serious infectious disease in birds, resulting in severe losses in the poultry industry every year. Haemagglutinin neuraminidase glycoprotein (HN) has been recognized as a key protein in the viral infection mechanism, and its inhibition represents an attractive target for the development of new drugs based on sialic acid glycals, with the 2-deoxy-2,3-didehydro-d-N-acetylneuraminic acid (Neu5Ac2en) as their backbone. Herein we report the synthesis of several Neu5Ac2en glycals and of their perfluorinated C-5 modified derivatives, including their respective stereoisomers at C-4, together with evaluation of their in vitro antiviral activity. While all synthesized compounds were found to be active HN inhibitors in the micromolar range, we found that their potency was influenced by the chain-length of the C-5 perfluorinated acetamido functionality. Thus, the binding modes of the inhibitors were also investigated by performing a docking study. Moreover, the perfluorinated glycals were found to be more active than the corresponding normal C-5 acylic derivatives. Finally, cell-cell fusion assays on NDV infected cells revealed that the addition of a newly synthesized C-4α heptafluorobutyryl derivative almost completely inhibited NDV-induced syncytium formation.
Synthesis of selective inhibitors against V. cholerae sialidase and human cytosolic sialidase NEU2
Khedri, Zahra,Li, Yanhong,Cao, Hongzhi,Qu, Jingyao,Yu, Hai,Muthana, Musleh M.,Chen, Xi
experimental part, p. 6112 - 6120 (2012/09/05)
Sialidases or neuraminidases catalyze the hydrolysis of terminal sialic acid residues from sialyl oligosaccharides and glycoconjugates. Despite successes in developing potent inhibitors specifically against influenza virus neuraminidases, the progress in designing and synthesizing selective inhibitors against bacterial and human sialidases has been slow. Guided by sialidase substrate specificity studies and sialidase crystal structural analysis, a number of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (DANA or Neu5Ac2en) analogues with modifications at C9 or at both C5 and C9 were synthesized. Inhibition studies of various bacterial sialidases and human cytosolic sialidase NEU2 revealed that Neu5Gc9N32en and Neu5AcN39N 32en are selective inhibitors against V. cholerae sialidase and human NEU2, respectively.
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
Nishino, Reiko,Ikeda, Kiyoshi,Hayakawa, Takuya,Takahashi, Tadanobu,Suzuki, Takashi,Sato, Masayuki
scheme or table, p. 2418 - 2427 (2011/05/12)
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.
Regio- and stereocontrolled palladium-catalyzed allylic substitution on n-acetylneuraminic acid derivatives
Chang, Chih-Wei,Norsikian, Stephanie,Guillot, Regis,Beau, Jean-Marie
experimental part, p. 2280 - 2294 (2010/07/10)
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.
Useful sialic acid modifications catalyzed by palladium
Chang, Chih-Wei,Norsikian, Stephanie,Beau, Jean-Marie
body text, p. 5195 - 5199 (2009/12/22)
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.
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
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)
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.
Phenylboronic acid as a labile protective agent: the selective derivatisation of 1,2,3-triols
Bhaskar, Vijaya K.,Duggan, Peter J.,Humphrey, David G.,Krippner, Guy Y.,McCarl, Victoria,Offermann, Daniel A.
, p. 1098 - 1102 (2007/10/03)
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.
Synthesis of a Neu2en5Ac analog hapten and isolation of monoclonal antibody to Neu2en5Ac
Kamei, Hiroya,Kajihara, Yasuhiro,Nishi, Yoshisuke
, p. 243 - 250 (2007/10/03)
Neu2en5Ac is a minor component of body fluids and is abundant in sialuria, but no antibody to detect it has been reported. 5-Acetamido-2,6-anhydro-9-glutaramido-3,5,9-trideoxy-D-glycero-D-galacto-non-2-enonic acid has been synthesized and conjugated with
8-O-Sialylation of neuraminic acid acceptor reactivity and anomeric stereocontrol
Castro-Palomino, Julio C.,Tsvetkov, Yury E.,Schneider, Regine,Schmidt, Richard R.
, p. 6837 - 6840 (2007/10/03)
2-O-unprotected and 2-deoxy-2,3-dehydro-neuraminic acid derivatives 2, 4, and 10 exhibit enhanced acceptor properties at their 8-hydroxy group in sialylation reactions with phosphite 5 as donor: yet, mainly (10) or exclusively (2, 4) β-glycoside bond formation was observed. The 3-phenylthionocarbonate group as stereodirecting auxiliary group in the sialyl donor 11 led with 10 as acceptor to exclusive formation of α(2-8)-linked disaccharide.
