Methyl and Benzyl (Ethyl 3,4-di-O-benzyl-2-O-benzoyl-1-thio-β-d-glucopyranosyl)uronate DOI Creative Commons
Hannah Wootton, Gavin J. Miller

Molbank, Journal Year: 2024, Volume and Issue: 2024(3), P. M1847 - M1847

Published: July 9, 2024

Methyl and benzyl (ethyl 3,4-di-O-benzyl-2-O-benzoyl-1-thio-β-D-glucopyranosyl)uronate were synthesised from a protected thioglycoside in three steps. A regioselective ring opening of the benzylidene acetal with BH3.THF generated C6-OH material, which was subsequently oxidised using biphasic TEMPO/BAIB conditions. The resultant uronic acid esterified either methyl or moiety. products obtained on multigram scale fully characterised by 1H, 13C 2D NMR, alongside MS IR analysis.

Language: Английский

Sugar-Coated: Can Multivalent Glycoconjugates Improve upon Nature’s Design? DOI Creative Commons
Kathryn G. Leslie,

Sian S. Berry,

Gavin J. Miller

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 28, 2024

Multivalent interactions between receptors and glycans play an important role in many different biological processes, including pathogen infection, self-recognition, the immune response. The growth number of tools techniques toward assembly multivalent glycoconjugates means it is possible to create synthetic systems that more closely resemble diversity complexity we observe nature. In this Perspective present background recognition binding enabled by nature, discuss strategies used construct glycoconjugate equivalents. We highlight key discoveries current state art their applications glycan arrays, vaccines, other therapeutic diagnostic tools, with outlook some areas believe are most interest for future work area.

Language: Английский

Citations

8
Automated Synthesis of Algal Fucoidan Oligosaccharides DOI Creative Commons
C. Crawford, Mikkel Schultz‐Johansen, Phuong Luong

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(27), P. 18320 - 18330

Published: June 25, 2024

Fucoidan, a sulfated polysaccharide found in algae, plays central role marine carbon sequestration and exhibits wide array of bioactivities. However, the molecular diversity structural complexity fucoidan hinder precise structure–function studies. To address this, we present an automated method for generating well-defined linear branched α-fucan oligosaccharides. Our syntheses include oligosaccharides with up to 20 cis-glycosidic linkages, diverse branching patterns, 11 sulfate monoesters. In this study, demonstrate utility these by (i) characterizing two endo-acting glycoside hydrolases (GH107), (ii) utilizing them as standards NMR studies confirm suggested structures algal fucoidans, (iii) developing microarray. This microarray enabled screening specificity four monoclonal antibodies (mAb) targeting fucoidan. It was that mAb BAM4 has cross-reactivity β-glucans, while BAM2 reactivity fucoidans 4-O-sulfate esters. Knowledge epitope provided evidence globally abundant diatom, Thalassiosira weissflogii, synthesizes homology those brown algae. Automated glycan assembly provides access These provide basis level investigations into fucoidan's roles medicine sequestration.

Language: Английский

Citations

5
Overview of the current procedures in synthesis of heparin saccharides DOI Creative Commons

Siran Zhao,

Tianji Zhang,

Ying Kan

et al.

Carbohydrate Polymers, Journal Year: 2024, Volume and Issue: 339, P. 122220 - 122220

Published: May 3, 2024

Natural heparin, a glycosaminoglycan consisting of repeating hexuronic acid and glucosamine linked by 1 → 4 glycosidic bonds, is the most widely used anticoagulant. To subvert dependence on animal sourced alternative methods to produce heparin saccharides, i.e., either heterogenous sugar chains similar natural or structurally defined oligosaccharides, are becoming hot subjects. Although success chemical synthesis pentasaccharide, fondaparinux, encourages proceed through approach generating homogenous product, synthesizing larger oligos still cumbersome beyond reach so far. Alternatively, chemoenzymatic pathway exhibited exquisite stereoselectivity glycosylation regioselectivity modification, with advantage skip tedious protection steps unavoidable in synthesis. However, scale drug production needed today not sight. In comparison, procedure de novo biosynthesis an organism could be ultimate goal. The main purpose this review summarize current available/developing strategies techniques, which expected provide comprehensive picture for saccharides replenish eventually replace derived products. approaches, methodologies discussed according procedures: building block preparation, chain elongation, backbone modification.

Language: Английский

Citations

4
Synthesis of Sulfated Carbohydrates – Glycosaminoglycans DOI

Rakesh Raigawali,

Sharath S. Vishweshwara,

Saurabh Anand

et al.

Handbook of experimental pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Towards the synthesis of a 2-deoxy-2-fluoro-d-mannose building block and characterisation of an unusual 2-S-phenyl anomeric pyridinium triflate salt via 1→2 S-migration DOI Creative Commons

Sean T Evans,

Graham J. Tizzard, Robert A. Field

et al.

Carbohydrate Research, Journal Year: 2024, Volume and Issue: 545, P. 109275 - 109275

Published: Sept. 13, 2024

Language: Английский

Citations

2
Synthesis of S-Glycoside Building Blocks as Mimetics of the Repeating d-GlcN-α-1,4-d-GlcA Heparan Sulfate Disaccharide DOI Creative Commons

Conor O’Shea,

Gavin J. Miller

Molecules, Journal Year: 2024, Volume and Issue: 29(23), P. 5809 - 5809

Published: Dec. 9, 2024

Heparan sulfate (HS), a sulfated linear carbohydrate that decorates the cell surface and extracellular matrix, is key regulator of biological processes. Owing to inherent structural complexity HS, structure-to-function studies with its ligands are required, materials improve understanding such interactions therefore high importance. Herein, synthesis novel

Language: Английский

Citations

1
Adaptable synthesis of chondroitin sulfate disaccharide subtypes preprogrammed for regiospecific O-sulfation DOI Creative Commons
Hannah Wootton,

Sian Berry,

Elaine L. Ferguson

et al.

Published: June 21, 2024

A divergent synthetic route to chondroitin sulfate (CS) disaccharide precursors, including rarer subtypes such as CS-D, has been developed. From common intermediates, a series of thioglycoside D-glucose donors and 4,6-O-benzylidene protected D-galactosamine acceptors are utilised in robust glycosylation reaction, achieving β-selectivity consistent yields (60-75%) on scales >2.0 g. post-glycosylation oxidation D-glucuronic acid orthogonal protecting groups delivers access CS-A, CS-C, CS-E CS-O precursor subtypes. Of further note is 4-O-benzyl regioselective reductive ring opening 4,6-O- benzylidene using PhBCl2 Et3SiH CS-D precursor, 73% yield over two steps. Finally, synthesis 6-O-sulfated CS-C containing conjugable anomeric allyl tether completed. These materials will provide benchmark synthesise study sulfates.

Language: Английский

Citations

0
Adaptable Synthesis of Chondroitin Sulfate Disaccharide Subtypes Preprogrammed for Regiospecific O‐Sulfation DOI Creative Commons
Hannah Wootton,

Sian S. Berry,

Elaine L. Ferguson

et al.

European Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 27(40)

Published: July 29, 2024

Abstract A divergent synthetic route to chondroitin sulfate (CS) disaccharide precursors, including rarer subtypes such as CS−D, has been developed. From common intermediates, a series of thioglycoside D‐glucosyl donors and 4,6‐ O ‐benzylidene protected D‐galactosamine acceptors are utilised in robust glycosylation reaction, achieving β‐selectivity consistent yields (60–75 %) on scales >2.0 g. post‐glycosylation oxidation D‐glucuronic acid orthogonal protecting groups delivers access CS−A, CS−C, CS−E CS−O precursor subtypes. Of further note is 4‐ ‐benzyl regioselective reductive ring opening using dichlorophenylborane (PhBCl 2 ) triethylsilane (Et 3 SiH) CS−D precursor, 73 % yield over two steps. Finally, synthesis 6‐ ‐sulfated CS−C containing conjugable anomeric allyl tether completed. These materials will provide benchmark synthesise study sulfates.

Language: Английский

Citations

0
Methyl and Benzyl (Ethyl 3,4-di-O-benzyl-2-O-benzoyl-1-thio-β-d-glucopyranosyl)uronate DOI Creative Commons
Hannah Wootton, Gavin J. Miller

Molbank, Journal Year: 2024, Volume and Issue: 2024(3), P. M1847 - M1847

Published: July 9, 2024

Methyl and benzyl (ethyl 3,4-di-O-benzyl-2-O-benzoyl-1-thio-β-D-glucopyranosyl)uronate were synthesised from a protected thioglycoside in three steps. A regioselective ring opening of the benzylidene acetal with BH3.THF generated C6-OH material, which was subsequently oxidised using biphasic TEMPO/BAIB conditions. The resultant uronic acid esterified either methyl or moiety. products obtained on multigram scale fully characterised by 1H, 13C 2D NMR, alongside MS IR analysis.

Language: Английский

Citations

0