Direct Synthesis of Unprotected C-Glycosides via Photoredox Activation of Glycosyl Ester

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Synthetic C-glycosides play a crucial role in molecular biology and medicine. With the surge of interest demand to provide efforts with sufficient feedstock, it is highly significant pursue novel methodologies access concise efficient manner. Here, we disclose an attractive strategy that diverges itself from conventional multistep reaction sequences involving manipulations protecting groups. Widely available native sugars first react 1,4-dihydropyridine acids via site-selective Mitsunobu reaction, converting them into bench-stable radical precursors. Under visible-light-enabled photoredox catalysis conditions, resulting glycosyl radicals undergo C–C bond formation reactions, yielding variety excellent stereoselectivity. Our method demonstrates good tolerance wide range functional groups has been successfully applied post-transformation drug molecules preparation C-glycosyl amino acids.

Language: Английский

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Nitrene-mediated glycosylation with thioglycoside donors under metal catalysis

Science Advances, Journal Year: 2025, Volume and Issue: 11(8)

Published: Feb. 21, 2025

Glycosylation chemistry plays a pivotal role in glycoscience. Recent substantial developments have poised the field to address emerging challenges related sustainability, cost efficiency, and robust applicability complex substrate settings. The transition from stoichiometric activation metal-catalyzed methods promises enhanced chemoselectivity greater precision controlling glycosidic bond breakage formation, key overcoming existing obstacles. Here, we report nitrene-mediated glycosylation strategy using regular aryl sulfide glycosyl donors easily accessible 3-methyl dioxazolone as an activator under catalysis of iron or ruthenium. iron-catalyzed system demonstrates exceptional catalytic reactivity, requiring little 0.1 mole % catalyst at room temperature, works well for peptide substrates. ruthenium-catalyzed can accommodate acid-sensitive functional groups challenging low-reactivity acceptors. Mechanistic investigations unveiled unusual multistep pathways involving sulfur imidation via nitrene transfer sulfur-to-oxygen rearrangement N-acyl sulfilimines donors.

Language: Английский

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Electrochemical Glycosylation via Halogen-Atom-Transfer for C-Glycoside Assembly

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(15), P. 11532 - 11544

Published: July 19, 2024

Glycosyl donor activation emerged as an enabling technology for anomeric functionalization, but aimed primarily at O-glycosylation. In contrast, we herein disclose mechanistically distinct electrochemical glycosyl bromide activations via halogen-atom transfer and C-glycosylation. The radical addition to alkenes led C-alkyl glycoside synthesis under precious metal-free reaction conditions from readily available bromides. robustness of our e-XAT strategy was further mirrored by C-aryl C-acyl glycosides assembly through nickela-electrocatalysis. Our approach provides orthogonal with expedient scope, hence representing a general method direct C-glycosides assembly.

Language: Английский

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C–OH Bond Activation for Stereoselective Radical C-Glycosylation of Native Saccharides

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(47), P. 32269 - 32275

Published: Nov. 15, 2024

Radical C-glycosylation presents a flexible and efficient method for synthesizing C-glycosides. Existing methods always require multistep processes generating anomeric radicals. In this study, we introduce streamlined approach to produce radicals through direct C-OH bond homolysis of unmodified saccharides, eliminating the need protection, deprotection, or activation steps. These selectively couple with activated alkenes, yielding products high stereoselectivity (>20:1). This is applicable variety native monosaccharides, such as l-arabinose, d-arabinose, d-xylose, l-xylose, d-galactose, β-d-glucose, α-d-glucose, l-ribose, well oligosaccharides including α-lactose, d-(+)-melibiose, acarbose. We also extend amino acid peptide derivatives, demonstrate synthesis an anti-inflammatory agent.

Language: Английский

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Iridium Photoredox-Catalyzed Stereoselective C-Glycosylation with Tetrafluoropyridin-4-yl Thioglycosides: A Facile Synthesis of C-α/β-Glucogallins and Their Antioxidant Activity

ACS Catalysis, Journal Year: 2024, Volume and Issue: unknown, P. 17727 - 17738

Published: Nov. 18, 2024

We demonstrate an efficient, scalable, and stereoselective C-glycosylation with thioglycosides possessing a unique photoactive tetrafluoropyridin-4-yl (TFPy) thio radical leaving group, affording editable medicinally biologically essential C-α-glucogallin derivatives. In the presence of silyl enol ether acceptors, desulfurative coupling reaction performs smoothly under mild conditions upon exposure to blue light irradiation. This versatile protocol permits synthesis sugar-drug chimeras by C1 ketonylation complex drug-derived ethers. The scale-up synthesis, anomeric epimerization, post-C-glycosylation modification ketone sugars showcase reaction's potential utilities. Furthermore, could be applied direct carbohydrate skeleton editing equipping group on nonanomeric position. is viable for unprotected TFPy thioglycoside, route ketonyl sugars. concise six-step assembly both configurated C-glucogallins from commercially cheap glucose pentaacetate their antioxidant reactivity investigations underline promising medicinal relevance our current protocols. mechanism was investigated through trapping experiment, oxocarbenium fluorescence quenching Stern–Volmer analysis, confirming that major glycosyl intermediates are generated thioglycoside donors, whose effectively quench excited Ir(ppy)3 oxidative process, complementary product, accounting examples moderate selectivities.

Language: Английский

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Emerging Advances of the Radical Pathway Glycosylation Enabled by Bench‐Stable Glycosyl Donors: Glycosyl Sulfoxides, Glycosyl Sulfones, and Glycosyl Sulfinates

Advanced Synthesis & Catalysis, Journal Year: 2024, Volume and Issue: 366(19), P. 4017 - 4041

Published: July 30, 2024

Abstract In synthetic carbohydrate chemistry, the modification of glycosyl radicals pathway stands as a central area focus. The radical‐based reactions often demonstrate remarkable compatibility with various functional groups owing to mild initiation conditions. particular, identification novel radical precursors, combined advanced reaction techniques, has substantially broadened scope compound synthesis. Despite presence versatile donors, synthesis noble donors is still addressed need and challenges associated sugar chemistry. Currently, new class precursors been developed which enables production C ‐, S O N ‐glycosides efficiently. this light, we highlight strategies towards bench‐stable sulfoxides, sulphone, sulfite that can enable site‐, regio‐ stereoselective transformation protected or naked synthons in Here, review article covers recent developments selective diversification such alkylation, arylation, alkenylation, sulfuration, C−H activation, DNA conjugation via along mechanistic aspects, challenges, future directions.

Language: Английский

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Regiodivergent Functionalization of Protected and Unprotected Carbohydrates using Photoactive 4‐Tetrafluoropyridinylthio Fragment as an Adaptive Activating Group

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(52)

Published: Aug. 29, 2024

Abstract The selective functionalization of carbohydrates holds a central position in synthetic carbohydrate chemistry, driving the ongoing quest for ideal approaches to manipulate these compounds. In this study, we introduce general strategy that enables regiodivergent saccharides. use electron‐deficient photoactive 4‐tetrafluoropyridinylthio (SPyf) fragment as an adaptable activating group, facilitated efficient across all saccharide sites. More importantly, group can be directly installed at C1, C5 and C6 positions biomass‐derived single step site‐selective manner, allowing precision‐oriented modification unprotected saccharides glycans.

Language: Английский

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Photocatalytic Synthesis of α-Ketonyl Glycosyl Compounds from Glycosyl Thiols and Silyl Enol Ethers

Organic Letters, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 19, 2024

The synthesis of C1-ketonyl glycosyl compounds featuring α-selectivity has seldom been reported. We herein devise a radical-based approach to facilely access stereoenriched ketonyl via an Ir photoredox-catalyzed desulfurative addition silyl enol ethers, using in situ-generated tetrafluoropyridinyl thioglycosides from 1-thiols as radical precursors. This protocol features readily prepared starting materials, mild conditions, excellent functional group tolerance, satisfactory scale-up, and notable amenability late-stage modification pharmaceutically relevant complex molecules.

Language: Английский

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C,N-Diaryl Glycosyl Imidates for Catalytic Glycosylation

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

We report the development of a novel class glycosyl donors, C,N-diaryl imidates, distinguished by presence two identical aryl groups. These DAIs are efficiently synthesized from imidoyl fluorides, which derived symmetrical benzophenone precursors. Among evaluated, donor featuring para-fluorophenyl groups exhibits exceptional versatility and efficiency, enabling high-yield glycosylation reactions across wide range acceptors. Key intermediates, including fluorides DAI strike an ideal balance between storage stability reactivity, underscoring their promise for streamlined synthesis complex saccharides.

Language: Английский

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Ligand-Enabled Selective Coupling of MIDA Boronates to Dehydroalanine-Containing Peptides and Proteins

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: 147(9), P. 7533 - 7544

Published: Feb. 21, 2025

α,β-dehydroalanine (ΔAla) is a uniquely reactive nonproteinogenic amino acid often employed for the late-stage functionalization of peptides, natural products (NPs), and proteins. The modification ΔAla powerful method semisynthetic engineering NPs post-translational protein mutagenesis. Numerous enabling techniques have been developed over years, but most state-of-the-art approaches furnish product mixtures detrimental in many applications. Here, we report Pd(II)-mediated coupling reaction between aryl N-methylimidodiacetic boronates ΔAla-containing peptides proteins which yields ΔzPhe with high selectivity. proceeds water under ambient conditions (37 °C, <24 h) without exclusion oxygen using fully unprotected substrates. speed selectivity enabled by use N,N'-ethylene-bis-Lthreonine as Pd(II) ligand. We utilize this chemistry to selectively functionalize variety oligopeptides, NP-like compounds, intact Finally, show that can be readily adapted modify vitro translated devising platform chemoribosomal synthesis ΔzPhe-containing structures. Altogether, our provides tool selective

Language: Английский

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