Facile Anomer-oriented Syntheses of 4-Methylumbelliferyl Sialic Acid Glycosides

10.26434/chemrxiv.14402576 ◽

2021 ◽

Author(s):

Abdullah Hassan ◽

Stefan Oscarson

Keyword(s):

Catalytic Activity ◽

Sialic Acid ◽

Substrate Specificity ◽

Enzymatic Activity ◽

Addition Reaction ◽

Neuraminic Acid ◽

Acetylneuraminic Acid ◽

Diastereoselective Addition ◽

High Yields ◽

Stereoselective Syntheses

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 from N-acetylneuraminic acid. Both α- and β-4-methylumbelliferyl sialic acid glycosides were prepared in high yields and excellent stereoselectivity. Alpha anomers were accessed via reagent control by utilising additive CH3CN and TBAI, whereas the beta 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.

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Kinetic studies on the acid hydrolysis of the methyl ketoside of unsubstituted and O-acetylated N-acetylneuraminic acid

Biochemical Journal ◽

10.1042/bj1330623 ◽

1973 ◽

Vol 133 (4) ◽

pp. 623-628 ◽

Cited By ~ 13

Author(s):

A. Neuberger ◽

Wendy A. Ratcliffe

Keyword(s):

Sialic Acid ◽

Acid Hydrolysis ◽

Model Compound ◽

Kinetic Studies ◽

Order Rate Constant ◽

Neuraminic Acid ◽

Acetylneuraminic Acid ◽

Rate Of Hydrolysis ◽

Ph Range ◽

Hydrolysis Of

The hydrolysis of the model compound 2-O-methyl-4,7,8,9-tetra-O-acetyl-N-acetyl-α-d-neuraminic acid and neuraminidase (Vibrio cholerae) closely resembled that of the O-acetylated sialic acid residues of rabbit Tamm–Horsfall glycoprotein. This confirmed that O-acetylation was responsible for the unusually slow rate of acid hydrolysis of O-acetylated sialic acid residues observed in rabbit Tamm–Horsfall glycoprotein and their resistance to hydrolysis by neuraminidase. The first-order rate constant of hydrolysis of 2-methyl-N-acetyl-α-d-neuraminic acid by 0.05m-H2SO4 was 56-fold greater than that of 2-O-methyl-4,7,8,9-tetra-O-acetyl-N-acetyl -α-d-neuraminic acid. Kinetic studies have shown that in the pH range 1.00–3.30, the observed rate of hydrolysis of 2-methyl-N-acetyl-α-d-neuraminic acid can be attributed to acid-catalysed hydrolysis of the negatively charged CO2− form of the methyl ketoside.

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The reactivities of human erythrocyte autoantibodies anti-Pr2, anti-Gd, Fl and Sa with gangliosides in a chromatogram binding assay

Biochemical Journal ◽

10.1042/bj2190865 ◽

1984 ◽

Vol 219 (3) ◽

pp. 865-874 ◽

Cited By ~ 29

Author(s):

K Uemura ◽

D Roelcke ◽

Y Nagai ◽

T Feizi

Keyword(s):

Sialic Acid ◽

Thin Layer ◽

Human Erythrocyte ◽

Binding Assay ◽

Neuraminic Acid ◽

Human Erythrocytes ◽

The Other ◽

Thin Layer Chromatogram ◽

Acetylneuraminic Acid ◽

Bovine Erythrocytes

The thin layer chromatogram binding assay was used to study the reaction of several natural-monoclonal autoantibodies which recognize sialic acid-dependent antigens of human erythrocytes. Immunostaining of gangliosides derived from human and bovine erythrocytes was achieved with four autoantibodies designated anti-Pr2, anti-Gd, Sa and Fl, each of which has a different haemagglutination pattern with untreated and proteinase-treated erythrocytes and with cells of I and i antigen types. From the chromatogram binding patterns of anti-Pr2 with gangliosides of the neolacto and the ganglio series, it is deduced that this antibody reacts best with N-acetylneuraminic acid when it is alpha 2-3- or alpha 2-6-linked to a terminal Gal(beta 1-4)Glc/GlcNAc GlcNAc sequence and to a lesser extent when it is alpha 2-3-linked to a terminal Gal(beta 1-3)GalNAc sequence or to an internal galactose and when it is alpha 2-8-linked to another, internal N-acetylneuraminic acid residue. The other three antibodies differ from anti-Pr2 in their lack of reaction with glycolipids of the ganglio series. They react with the NeuAc(alpha 2-3)Gal(beta 1-4)Glc/GlcNAc sequence as found in GM3 and in glycolipids of the neolacto series, but show a preference for the latter, longer sequences. Thus all four antibodies react with sialylated oligosaccharides containing i type (linear) and I type (branched) neolacto backbones. Fl antibody differs from the other three in its stronger reaction with branched neolacto sequences in accordance with its stronger agglutination of erythrocytes of I rather than i type. The four antibodies show a specificity for N-acetyl- rather than N-glycolyl-neuraminic acid.

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Synthesis and Antiproliferative Evaluation of 2-Deoxy-N-glycosylbenzotriazoles/imidazoles

Molecules ◽

10.3390/molecules26123742 ◽

2021 ◽

Vol 26 (12) ◽

pp. 3742

Author(s):

Caleigh S. Garton ◽

Noelle K. DeRose ◽

Dylan Dominguez ◽

Maria L. Turbi-Henderson ◽

Ashley L. Lehr ◽

...

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Addition Reaction ◽

Protecting Group ◽

Human Breast ◽

Lung Cancer Cell ◽

Subsequent Removal ◽

Anticancer Properties ◽

Tributyltin Hydride ◽

High Yields

A series of 2-deoxy-2-iodo-α-d-mannopyranosylbenzotriazoles was synthesized using the benzyl, 4,6-benzylidene and acetyl protected D-glucal in the presence of N-iodosuccinimide (NIS). Subsequent removal of the iodine at the C-2 position using tributyltin hydride under free radical conditions afforded the 2-deoxy-α-d-glucopyranosylbenzotriazoles in moderate to high yields. This method was extended to the preparation of substituted 2-deoxy-β-d-glucopyranosylimidazoles as well. The stereoselectivity of the addition reaction and the effect of the protecting group and temperature on anomer distribution of the benzotriazole series were also investigated. The anticancer properties of the newly synthesized compounds were evaluated in a series of viability studies using HeLa (human cervical adenocarcinoma), human breast and lung cancer cell lines. The N-[3,4,6-tri-O-benzyl-2-deoxy-α-d-glucopyranosyl]-1H-benzotriazole and the N-[3,4,6-tri-O-acetyl-2-deoxy-α-d-glucopyranosyl]-2H-benzotriazole were found to be the most potent cancer cell inhibitors at 20 µM concentrations across all four cell lines.

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