Diastereoselective Synthesis of Aryl C‐Glycosides from Glycosyl Esters via C−O Bond Homolysis

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(17), P. 9433 - 9438

Published: Jan. 15, 2021

C-aryl glycosyl compounds offer better in vivo stability relative to O- and N-glycoside analogues. glycosides are extensively investigated as drug candidates applied chemical biology studies. Previously, were derived from lactones, glycals, stannanes, halides, via methods displaying various limitations with respect the scope, functional-group compatibility, practicality. Challenges remain synthesis of nucleosides 2-deoxysugars easily accessible carbohydrate precursors. Herein, we report a cross-coupling method prepare heteroaryl glycosides, including 2-deoxysugars, esters bromoarenes. Activation substrates leverages dihydropyridine (DHP) an activating group followed by decarboxylation generate radical C-O bond homolysis. This strategy represents new means activate alcohols partner. The convenient preparation their exemplifies potential this medicinal chemistry.

Language: Английский

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Visible light activation enables desulfonylative cross-coupling of glycosyl sulfones

Nature Synthesis, Journal Year: 2022, Volume and Issue: 1(12), P. 967 - 974

Published: Sept. 22, 2022

Language: Английский

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Diversification of Glycosyl Compounds via Glycosyl Radicals

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(38)

Published: June 7, 2023

Glycosyl radical functionalization is one of the central topics in synthetic carbohydrate chemistry. Recent advances metal-catalyzed cross-coupling chemistry and metallaphotoredox catalysis provided powerful platforms for glycosyl diversification. In particular, discovery new precursors conjunction with these advanced reaction technologies have significantly expanded space compound synthesis. this Review, we highlight most recent progress area starting from 2021, reports included will be categorized based on different types better clarity.

Language: Английский

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Radical Pathway Glycosylation Empowered by Bench-Stable Glycosyl Donors

Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 56(18), P. 2473 - 2488

Published: Aug. 18, 2023

ConspectusThe study of carbohydrates has emerged as a crucial research area in various disciplines due to their pivotal roles cellular processes. To facilitate in-depth exploration biological functions, chemical glycosylation reactions that allow facile access glycoconjugates broad community are highly needed. In classical reactions, glycosyl donor is activated by an acid generate reactive electrophilic intermediate, which subsequently forms glycosidic bond upon reaction with nucleophilic acceptor. Such ionic pathway been the mainstay technique for glycoconjugate synthesis and allowed numerous intricate structures. Nevertheless, limitations still exist. For instance, when labile donors or harsh activating conditions required, these methods show limited tolerance hydroxyl groups abundant on sugar rings. addition, achieving good stereocontrol represents another longstanding obstacle. recent years, new modes activation have sought tackle above challenges.We noted passing through intermediacy radicals via cascade single-electron transfer steps possess significant but underexplored potential. Progress this slow large part dearth handy maneuver radicals. Most existing call either forcing unstable/inconvenient starting materials. order better exploit power radical glycosylation, we developed range donors─namely, sulfoxides, sulfones, sulfinates─that bench stable can be readily prepared from simple These form under mild conditions. Enabled use donors, series could used making O-, S-, C-glycosides, some were previously difficult access. many cases, no protecting group required. As illustration potential utility, our adopted preparation sugar–drug conjugates, sugar–DNA glycopeptides, even glycoproteins. While most cases intrinsic reactivity intermediates explored axially configured products, also utilization external, delicate reagents, catalysts override such innate preference achieve catalyst-controlled stereoselectivity.We believe enormous inspire development novel glycoside synthesis. Account, highlight design principles summarize advancements enabled use, provide outlook future directions 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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Direct Formation of Amide-Linked C-Glycosyl Amino Acids and Peptides via Photoredox/Nickel Dual Catalysis

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(8), P. 5502 - 5510

Published: Feb. 15, 2024

Glycoproteins account for numerous biological processes including those associated with diseases and infections. The advancement of glycopeptides has emerged as a promising strategy unraveling pathways discovering novel medicines. In this arena, key challenge arises from the absence efficient synthetic strategies to access glycoproteins. Here, we present highly concise approach bridging saccharides amino acids peptides through an amide linkage. Our amide-linked C-glycosyl are synthesized cooperative Ni-catalyzed photoredox processes. catalytic process generates glycosyl radical carbonyl radical, which subsequently combine yield products. saccharide reaction partners encompass mono-, di-, trisaccharides. All 20 natural acids, peptides, their derivatives can efficiently undergo glycosylations yields ranging acceptable high, demonstrating excellent stereoselectivities. As substantial expansion applications, have shown that simple function versatile building units constructing C-glycopeptides intricate spatial complexities.

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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Nonenzymatic StereoselectiveS-Glycosylation of Polypeptides and Proteins

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(31), P. 11919 - 11926

Published: July 29, 2021

Here we report a nonenzymatic glycosylation reaction that builds axial S-glycosidic bonds under biorelevant conditions. This strategy is enabled by the design and use of allyl glycosyl sulfones as precursors to radicals exploits exceptional functional group tolerance radical processes. Our method introduces variety unprotected units cysteine residues peptides in highly selective fashion. Through developing second-generation protocol, applied our direct complex polypeptides proteins. Computational studies were performed elucidate mechanism.

Language: Английский

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Stereoselective Synthesis of C‐Vinyl Glycosides via Palladium‐Catalyzed C−H Glycosylation of Alkenes

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(36), P. 19620 - 19625

Published: July 6, 2021

C-vinyl glycosides are an important class of carbohydrates and pose a unique synthetic challenge. A new strategy has been developed for stereoselective synthesis via Pd-catalyzed directed C-H glycosylation alkenes with glycosyl chloride donors using easily removable bidentate auxiliary. Both the γ bond allylamines δ homoallyl amine substrates can be glycosylated in high efficiency excellent regio- stereoselectivity. The resulting further converted to variety C-alkyl stereospecificity. These reactions offer broadly applicable method streamline complex from accessible starting materials.

Language: Английский

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Visible‐Light‐Promoted Stereoselective C(sp³)−H Glycosylation for the Synthesis of C‐Glycoamino Acids and C‐Glycopeptides

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(24)

Published: March 22, 2022

The glycosylative modification of peptides could improve the pharmacological properties peptide drugs and deliver them efficiently to target sites. Compared with O-/N-glycosides, C-glycosides exhibit more metabolic stability. We here disclose first example visible-light-promoted Cu-catalyzed stereoselective C-glycosylation. mild reaction conditions are compatible various carbohydrate substrates, as demonstrated a series monosaccharides disaccharide, amenable synthesis wide variety C-glycoamino acids C-glycopeptidomimetics good yields excellent stereoselectivities. dual-functional photocatalyst formed in situ via coordination glycine derivative chiral phosphine Cu complex not only catalyze photoredox process but also control stereoselectivity glycosylation reaction.

Language: Английский

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