Automated Chemical Oligosaccharide Synthesis: Novel Approach to Traditional Challenges

Chemical Reviews, Journal Year: 2018, Volume and Issue: 118(17), P. 8105 - 8150

Published: June 28, 2018

Advances in carbohydrate chemistry have certainly made common oligosaccharides much more accessible. However, many current methods still rely heavily upon specialized knowledge of chemistry. The application automated technologies to chemical and life science applications such as genomics proteomics represents a vibrant field. These also present opportunities for their organic synthesis, including that the synthesis oligosaccharides. carbohydrates is an underdeveloped area compared other classes biomolecules. overarching goal this review article advances been at interface technology.

Language: Английский

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Site-Selective Functionalization of Hydroxyl Groups in Carbohydrate Derivatives

Chemical Reviews, Journal Year: 2018, Volume and Issue: 118(23), P. 11457 - 11517

Published: Dec. 3, 2018

Methods for site-selective transformations of hydroxyl groups in carbohydrate derivatives are reviewed. The construction oligosaccharides defined connectivity hinges on such transformations, which also needed the preparation modified or non-natural sugar derivatives, installation naturally occurring postglycosylation modifications, selective labeling conjugation and therapeutic agents research tools glycobiology. review begins with a discussion intrinsic factors processes that can influence selectivity reactions unprotected partially protected followed by description engage two OH cyclic adducts (acetals, ketals, boronic esters, related species). An overview various classes sugars is then provided: discussed include esterification, thiocarbonylation, alkylation, glycosylation, arylation, silylation, phosphorylation, sulfonylation, sulfation, oxidation. Emphasis placed recently developed methods employ reagent catalyst control to achieve otherwise challenging site-selectivities.

Language: Английский

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Oligosaccharide Synthesis and Translational Innovation

Journal of the American Chemical Society, Journal Year: 2019, Volume and Issue: 141(9), P. 3735 - 3754

Published: Feb. 4, 2019

The translation of biological glycosylation in humans to the clinical applications involves systematic studies using homogeneous samples oligosaccharides and glycoconjugates, which could be accessed by chemical, enzymatic or other methods. However, structural complexity wide-range variations glycans their conjugates represent a major challenge synthesis this class biomolecules. To help navigate within many methods oligosaccharide synthesis, Perspective offers critical assessment most promising synthetic strategies with an eye on therapeutically relevant targets.

Language: Английский

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Automated Glycan Assembly: A Perspective

Journal of the American Chemical Society, Journal Year: 2019, Volume and Issue: 141(14), P. 5581 - 5592

Published: March 19, 2019

The intrinsic complexity of carbohydrate structures has hampered access to pure glycans and hence impeded progress in the glycosciences. Automated Glycan Assembly (AGA) facilitated procurement synthetic glycans, be used diagnostics, vaccine development, enzyme characterization structure-function relationship studies. A general approach for obtaining complex from mammalian, bacterial, fungal plant classes provides molecular tools glycobiology research. Recent advances AGA technology pave way production novel materials. This perspective describes state-of-the art aspects where additional improvements are needed.

Language: Английский

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Automated solution-phase multiplicative synthesis of complex glycans up to a 1,080-mer

Nature Synthesis, Journal Year: 2022, Volume and Issue: 1(11), P. 854 - 863

Published: Sept. 29, 2022

Language: Английский

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ortho-Methoxycarbonylethynylphenyl Thioglycosides (MCEPTs): Versatile Glycosyl Donors Enabled by Electron-Withdrawing Substituents and Catalyzed by Gold(I) or Cu(II) Complexes

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(6), P. 3682 - 3695

Published: Feb. 2, 2023

With easily accessible and operator-friendly reagents, shelf-stable ortho-methoxycarbonylethynylphenyl thioglycosides were efficiently prepared. Based on these MCEPT glycoside donors, a novel glycosylation protocol featuring mild catalytic promotion conditions with Au(I) or Cu(II) complexes, expanded substrate scope encompassing challenging donors acceptors clinically used pharmaceuticals, versatility in various strategies for highly efficient synthesis of glycosides has been established. The practicality the was fully exhibited by scalable surface polysaccharide subunits Acinetobacter baumannii via latent-active, reagent-controlled divergent orthogonal one-pot strategies. underlying reaction mechanism investigated systematically through control reactions, leading to isolation characterization vital catalyst species glycosylation, benzothiophen-3-yl-gold(I) complex. results obtained both from reactions studies establishment, an operative proposed effect reactivity metal-catalyzed alkyne-containing donor-involved disclosed. Moreover, C-glycosylation side product formation ortho-(substituted)ethynylphenyl thioglycoside electron-donating substituents also illuminated.

Language: Английский

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Advances in glycoside and oligosaccharide synthesis

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(22), P. 7773 - 7801

Published: Jan. 1, 2023

The structural complexity of glycans poses a serious challenge in the chemical synthesis glycosides, oligosaccharides and glycoconjugates. Glycan complexity, determined by composition, connectivity, configuration far exceeds what nature achieves with nucleic acids proteins. Consequently, glycoside ranks among most complex tasks organic synthesis, despite involving only simple type bond-forming reaction. Here, we introduce fundamental principles bond formation summarize recent advances oligosaccharide synthesis.

Language: Английский

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Direct radical functionalization of native sugars

Nature, Journal Year: 2024, Volume and Issue: 631(8020), P. 319 - 327

Published: June 19, 2024

Abstract Naturally occurring (native) sugars and carbohydrates contain numerous hydroxyl groups of similar reactivity 1,2 . Chemists, therefore, rely typically on laborious, multi-step protecting-group strategies 3 to convert these renewable feedstocks into reagents (glycosyl donors) make glycans. The direct transformation native complex saccharides remains a notable challenge. Here we describe photoinduced approach achieve site- stereoselective chemical glycosylation from widely available sugar building blocks, which through homolytic (one-electron) chemistry bypasses unnecessary group masking manipulation. This process is reminiscent nature in its regiocontrolled generation transient glycosyl donor, followed by radical-based cross-coupling with electrophiles activation light. Through selective anomeric functionalization mono- oligosaccharides, this protecting-group-free ‘cap glycosylate’ offers straightforward access wide array metabolically robust compounds. Owing biocompatibility, the method was extended post-translational proteins.

Language: Английский

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Synthetic carbohydrate-based vaccines: challenges and opportunities

Journal of Biomedical Science, Journal Year: 2020, Volume and Issue: 27(1)

Published: Jan. 3, 2020

Abstract Glycoconjugate vaccines based on bacterial capsular polysaccharides (CPS) have been extremely successful in preventing infections. The glycan antigens for the preparation of CPS glycoconjugate are mainly obtained from fermentation, quality and length glycans always inconsistent. Such kind situation make CMC difficult to well control. Thanks advantage synthetic methods carbohydrates syntheses. controlled more easily obtain, them conjugated carrier protein so-call homogeneous fully vaccines. Several different phases clinical trial bacteria or cancers. review will introduce recent development vaccine.

Language: Английский

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Glycosyl ortho-(1-phenylvinyl)benzoates versatile glycosyl donors for highly efficient synthesis of both O-glycosides and nucleosides

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Jan. 21, 2020

Abstract Both of O -glycosides and nucleosides are important biomolecules with crucial rules in numerous biological processes. Chemical synthesis is an efficient scalable method to produce well-defined pure carbohydrate-containing molecules for deciphering their functions developing therapeutic agents. However, the development glycosylation methods both one long-standing challenges chemistry. Here, we report a highly versatile nucleosides, which uses glycosyl ortho -(1-phenylvinyl)benzoates as donors. This protocol enjoys various features, including readily prepared stable donors, cheap available promoters, mild reaction conditions, good excellent yields, broad substrate scopes. In particular, applications current demonstrated by one-pot several bioactive oligosaccharides drugs capecitabine, galocitabine doxifluridine.

Language: Английский

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