Radical Pathway Glycosylation Empowered by Bench-Stable Glycosyl Donors

Accounts of Chemical Research, Год журнала: 2023, Номер 56(18), С. 2473 - 2488

Опубликована: Авг. 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.

Язык: Английский

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Palladium catalysis enables cross-coupling–like S _N 2-glycosylation of phenols

Science, Год журнала: 2023, Номер 382(6673), С. 928 - 935

Опубликована: Ноя. 23, 2023

Despite their importance in life and material sciences, the efficient construction of stereo-defined glycosides remains a challenge. Studies carbohydrate functions would be advanced if glycosylation methods were as reliable modular palladium (Pd)-catalyzed cross-coupling. However, Pd-catalysis excels forming sp 2 -hybridized carbon centers whereas mostly builds 3 C–O linkages. We report platform through Pd-catalyzed S N displacement from phenols toward bench-stable, aryl-iodide–containing glycosyl sulfides. The key Pd(II) oxidative addition intermediate diverges an arylating agent (Csp electrophile) to glycosylating electrophile). This method inherits many merits cross-coupling reactions, including operational simplicity functional group tolerance. It preserves mechanism for various substrates is amenable late-stage commercial drugs natural products.

Язык: Английский

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Synergistic catalysis: An emerging concept for selective carbohydrate synthesis

Chem Catalysis, Год журнала: 2024, Номер 4(3), С. 100891 - 100891

Опубликована: Янв. 18, 2024

Harnessing modern catalytic concepts to address long-standing challenges in carbohydrate chemistry has garnered substantial interest from the synthetic community recent years. In particular, usage of multiple catalysts for sequential one-pot relay reactions already contributed major benefits accessing oligosaccharides past two decades. contrast, exploitation synergistic catalysis glycosciences is only its infancy. While methods combine stepwise into a single flask operation, they do not intrinsically alter reaction mechanisms. Conversely, involves creation unique mechanistic pathways by merging cycles. At nexus cycles, fertile opportunities arise bond-forming strategies that are possible within individual manifold. The realization underexploited potential expected accelerate developments field, thereby offering stereoselective entry points glycosidic chemical space was previously inaccessible.

Язык: Английский

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Base‐Promoted Glycosylation Allows Protecting Group‐Free and Stereoselective O‐Glycosylation of Carboxylic Acids**

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(42)

Опубликована: Авг. 17, 2023

Here we report a simple and general method to achieve fully unprotected, stereoselective glycosylation of carboxylic acids, employing bench-stable allyl glycosyl sulfones as donors. Running the reaction under basic conditions was crucial for efficiencies selectivities. Both donor activation stage glycosidic bond forming process are compatible with free hydroxyl groups, thereby allowing use unprotected This transformation is stereoconvergent, occurs mild metal-free at ambient temperature visible light (455 nm) irradiation, displays remarkable scope respect both partners. Many natural products commercial drugs, including an acid derived from complex anticancer agent taxol, were efficiently glycosylated. Experimental studies provide insights into origin stereochemical outcome.

Язык: Английский

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Palladium-Catalyzed O-Glycosylation through π–π Interactions

Organic Letters, Год журнала: 2024, Номер 26(25), С. 5396 - 5401

Опубликована: Июнь 13, 2024

A stereodivergent synthesis of β- and α-O-glycosides using 3-O-quinaldoyl glucals was developed by palladium catalysis at 60 110 °C respectively. Various alcohols, monosaccharides, amino acid were glycosylated to form α- products in good yields with high stereoselectivity. Mechanistic studies indicated no classic Pd–N (quinoline) coordination, but π–π stacking interactions promoted the anomeric stereodiversity. The practicality demonstrated glycosylating natural products/drugs synthesizing a complex tetrasaccharide.

Язык: 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, Год журнала: 2024, Номер 366(19), С. 4017 - 4041

Опубликована: Июль 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.

Язык: Английский

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Cooperative Catalysis in Stereoselective O- and N-Glycosylations with Glycosyl Trichloroacetimidates Mediated by Singly Protonated Phenanthrolinium Salt and Trichloroacetamide

Journal of the American Chemical Society, Год журнала: 2024, Номер unknown

Опубликована: Дек. 4, 2024

The development of small-molecule catalysts that can effectively activate both reacting partners simultaneously represents a pivotal pursuit in advancing the field stereoselective glycosylation reactions. We report herein singly protonated form readily available phenanthroline as an effective cooperative catalyst facilitates coupling wide variety aliphatic alcohols, phenols, and aromatic amines with α-glycosyl trichloroacetimidate donors. reaction likely proceeds via SN2-like mechanism, generating β-selective glycoside products. developed protocol provides access to O- N-glycosides good yields excellent levels β-selectivity enables late-stage functionalization cross-coupling Importantly, this method exhibits is unattainable through C2-O-acyl neighboring group participation strategy, especially case glycosyl donors already containing C2 heteroatom or sugar unit. Kinetic studies demonstrate byproduct trichloroacetamide plays previously undiscovered role influencing reactivity selectivity reaction. A proposed mechanism involving simultaneous activation donor acceptor by phenanthrolinium salt assistance supported kinetic analysis preliminary computational studies. This catalysis process involves four consecutive hydrogen bond interactions. first interaction occurs between carbonyl oxygen hydroxyl alcohol nucleophile (C═O···HO). second trichloroacetamide-NH2 forming nitrogen atom (NH···N). third (═NH) engaging phenanthrolinium-NH (NH···N═H). Lastly, trichloroacetimidate-NH2 forms fluorine tetrafluoroborate ion.

Язык: Английский

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Reaction Rate and Stereoselectivity Enhancement in Glycosidations with O-Glycosyl Trihaloacetimidate Donors due to Catalysis by a Lewis Acid–Nitrile Cooperative Effect

The Journal of Organic Chemistry, Год журнала: 2024, Номер 89(11), С. 7865 - 7876

Опубликована: Май 28, 2024

Activation of O-glycosyl trihaloacetimidate glycosyl donors with AuCl3 as a catalyst and pivalonitrile (tBuCN) ligand led to excellent glycosidation results in terms yield anomeric selectivity. In this way, various β-d-gluco- β-d-galactopyranosides were obtained conveniently efficiently. Experimental studies density functional theory (DFT) calculations, order elucidate the reaction course, support formation tBuCN–AuCl2–OR(H)+ AuCl4– complex decisive intermediate event. Proton transfer from acceptor imidate nitrogen leads donor activation. guided by C-2 configuration donor, alignment enforces stereoselective β-glycoside an intramolecular fashion, thus promoting also fast course. The high stereocontrol novel 'Lewis acid–nitrile cooperative effect' is independent without neighboring group or remote participation. power methodology shown successful glycoalkaloid solamargine synthesis.

Язык: Английский

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A transition-metal-free 1,10-phenanthroline-promoted homocoupling reaction for the construction of biaryl diamides

Tetrahedron, Год журнала: 2025, Номер unknown, С. 134562 - 134562

Опубликована: Фев. 1, 2025

Язык: Английский

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Minimally Protected and Stereoselective O-Glycosylation of Carboxylic Acid Allows Rapid Access to α-1-O- and 2-O-Acyl Glycosides

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Март 31, 2025

We herein reported a catalytic, minimally protected, and highly α-stereoselective glycosylation protocol using carboxylic acid as an acceptor glycosyl 8-alkynyl-1-naphthoate donor, enabling efficient access to unprotected α-1-O- 2-O-acyl glycosides. This method demonstrates excellent functional compatibility scope generality, allowing for the of wide range complex acids. Notably, we successfully synthesized two natural products, α-penta-O-galloyl-d-glucopyranose nyctanthesin A, this protocol. Mechanistic studies highlighted crucial role 1-O ester functionality in ensuring chemoselectivity important contribution 2-O facilitating reaction.

Язык: Английский

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