Catalytic Approaches to Chemo- and Site-Selective Transformation of Carbohydrates

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(10), P. 6793 - 6838

Published: April 26, 2023

Carbohydrates are a fundamental unit playing pivotal roles in all the biological processes. It is thus essential to develop methods for synthesizing, functionalizing, and manipulating carbohydrates further understanding of their functions creation sugar-based functional materials. is, however, not trivial such methods, since densely decorated with polar similarly reactive hydroxy groups stereodefined manner. New approaches chemo- site-selective transformations are, therefore, great significance revolutionizing sugar chemistry enable easier access sugars interest. This review begins brief overview innate reactivity carbohydrates. followed by discussions about catalytic enhance, override, or be orthogonal transformation avoids making list reactions, but rather focuses on summarizing concept behind each reported transformation. The literature references were sorted into sections based underlying ideas approaches, which we hope will help readers have better sense current state innovative field.

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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N-glycoside synthesis through combined copper- and photoredox-catalysed N-glycosylation of N-nucleophiles

Nature Synthesis, Journal Year: 2024, Volume and Issue: 3(5), P. 623 - 632

Published: March 1, 2024

Language: Английский

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Carbene-catalyzed chirality-controlled site-selective acylation of saccharides

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

Acylation stands as a fundamental process in both biological pathways and synthetic chemical reactions, with acylated saccharides their derivatives holding diverse applications ranging from bioactive agents to building blocks. A longstanding objective organic synthesis has been the site-selective acylation of without extensive pre-protection alcohol units. In this study, we demonstrate that by simply altering chirality N-heterocyclic carbene (NHC) catalysts, site-selectivity saccharide reactions can be effectively modulated. Our investigation reveals intriguing selectivity shift stems combination factors, including match/mismatch inter- / intramolecular hydrogen bonding between NHC catalyst substrates. These findings provide valuable insights into design reaction engineering, highlighting potential glycoside analysis, such fluorescent labelling, α/β identification, orthogonal selective late-stage modifications. The units synthesis. Here, authors

Language: Английский

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C‐GlycosideSynthesis Enabled by Nickel Catalysis

Chinese Journal of Chemistry, Journal Year: 2023, Volume and Issue: 41(17), P. 2217 - 2236

Published: April 13, 2023

Comprehensive Summary C‐Glycosides are critical, naturally occurring products and medicinal candidates, extensive efforts have been made to explore efficient approaches for creating C‐glycosidic bonds. Transition‐metal‐catalysis, particularly nickel‐catalyzed C‐glycosylation reactions constitute a promising strategy. However, achieving stereoselective synthesis of α‐ β‐C‐glycosides has long‐standing challenge. To address this problem, variety nickel‐mediated strategies developed. This review highlights recent developments in the diastereoselective briefly summarizes mechanistic understandings these methods.

Language: Английский

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Site-Selective C–O Bond Editing of Unprotected Saccharides

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 146(1), P. 824 - 832

Published: Dec. 20, 2023

Glucose and its polyhydroxy saccharide analogs are complex molecules that serve as essential structural components in biomacromolecules, natural products, medicines, agrochemicals. Within the expansive realm of saccharides, a significant area research revolves around chemically transforming naturally abundant units to intricate or uncommon such oligosaccharides rare sugars. However, partly due presence multiple hydroxyl groups with similar reactivities complexities arising from stereochemistry, transformation unprotected sugars desired target remains challenging. One formidable challenge lies efficient selective activation modification C–O bonds saccharides. In this study, we disclose modular 2-fold "tagging–editing" strategy allows for direct editing enabling rapid preparation valuable drug derivatives. The first step, referred "tagging", involves catalytic site-selective installation photoredox active carboxylic ester group specific unit an sugar. second namely, "editing", features bond cleavage form carbon radical intermediate undergoes further transformations C–H C–C formations. Our constitutes most effective shortest route medicines other bearing

Language: Английский

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Direct Identification of Complex Glycans via a Highly Sensitive Engineered Nanopore

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(19), P. 13356 - 13366

Published: April 11, 2024

The crucial roles that glycans play in biological systems are determined by their structures. However, the analysis of glycan structures still has numerous bottlenecks due to inherent complexities. nanopore technology emerged as a powerful sensor for DNA sequencing and peptide detection. This significant impact on development related research area. Currently, nanopores beginning be applied detection simple glycans, but complex this is challenging. Here, we designed an engineered α-hemolysin M113R/T115A achieve sensing at micromolar concentrations under label-free conditions. By extracting characteristic features depict three-dimensional (3D) scatter plot, with different numbers functional groups, various chain lengths ranging from disaccharide decasaccharide, distinct glycosidic linkages could distinguished. Molecular dynamics (MD) simulations show behaviors β1,3- or β1,4-glycosidic bonds nanopores. More importantly, system permitted discrimination each isomer mixture separation ratio over 0.9. work represents proof-of-concept demonstration can analyzed using technology.

Language: Английский

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Integrated chemoenzymatic synthesis of a comprehensive sulfated ganglioside glycan library to decipher functional sulfoglycomics and sialoglycomics

Nature Chemistry, Journal Year: 2024, Volume and Issue: 16(6), P. 881 - 892

Published: June 1, 2024

Language: Английский

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A Fluorinated Sialic Acid Vaccine Lead Against Meningitis B and C

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(22), P. 15366 - 15375

Published: May 20, 2024

Inspired by the specificity of α-(2,9)-sialyl epitopes in bacterial capsular polysaccharides (CPS), a doubly fluorinated disaccharide has been validated as vaccine lead against Neisseria meningitidis serogroups C and/or B. Emulating importance fluorine drug discovery, this molecular editing approach serves multitude purposes, which range from controlling α-selective chemical sialylation to mitigating competing elimination. Conjugation disialoside with two carrier proteins (CRM197 and PorA) enabled semisynthetic be generated; was then investigated six groups mice. The individual levels antibodies formed were compared classified highly glycan-specific protective. All glycoconjugates induced stable long-term IgG response binding native CPS epitope achieved. generated protective MenC MenB; vitro SBA OPKA assays. By merging glycan an outer cell membrane protein MenB, bivalent both created. It is envisaged that validation synthetic, bioisostere potent antigen will open new therapeutic avenues.

Language: Английский

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Sugar-Coated: Can Multivalent Glycoconjugates Improve upon Nature’s Design?

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

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