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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Linkage-Editing Pseudo-Glycans: A Reductive α-Fluorovinyl-C-Glycosylation Strategy to Create Glycan Analogs with Altered Biological Activities

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(3), С. 2237 - 2247

Опубликована: Янв. 10, 2024

The acetal (O-glycoside) bonds of glycans and glycoconjugates are chemically biologically vulnerable, therefore C-glycosides interest as more stable analogs. We hypothesized that, if the O-glycoside linkage plays a vital role in glycan function, biological activities C-glycoside analogs would vary depending on their substituents. Based this idea, we adopted "linkage-editing strategy" for creation (pseudo-glycans). designed three types pseudo-glycans with CH2 CHF linkages, which resemble terms bond lengths, angles, bulkiness, synthesized them efficiently by means fluorovinyl C-glycosylation selective hydrogenation reactions. Application strategy to isomaltose (IM), an inducer amylase expression, α-GalCer, activates iNKT cells, resulted discovery CH2-IM, shows increased production ability, CHF-α-GalCer, activity opposite that native serving antagonist cells.

Язык: Английский

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Diverse Synthesis of C-Glycosides by Stereoselective Ni-Catalyzed Carboboration of Glycals

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(28), С. 18866 - 18872

Опубликована: Июль 5, 2024

C-Glycosides are important structures that common to natural products and pharmaceutical agents. Established methods for their synthesis involve the reaction of an activated anomeric carbon. In this study, we report a conceptually new approach involves stereoselective Ni-catalyzed carboboration glycals. these reactions, not only is C–C bond formed at carbon, but synthetically useful C–B also installed. Upon oxidation, differentially protected C-glycosides be formed. addition, stereospecific manipulation leads diverse C-glycosides. Finally, application method in established C-glycosides, such as C-glycosyl amino acids, well strategy make all possible diastereomers C1 C2.

Язык: Английский

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Exploiting π and Chalcogen Interactions for the β‐Selective Glycosylation of Indoles through Glycal Conformational Distortion

Angewandte Chemie International Edition, Год журнала: 2023, Номер 63(7)

Опубликована: Дек. 20, 2023

Harnessing unconventional noncovalent interactions (NCIs) is emerging as a formidable synthetic approach in difficult-to-access glycosidic chemical space. C-Glycosylation, particular, has gained flurry of recent attention. However, most reported methods are restricted to the relatively facile access α-C-glycosides. Herein, we disclose β-stereoselective glycosylation indoles by employing phosphonoselenide catalyst. The robustness this protocol exemplified its amenability for reaction at both indolyl C- and N- reactivity sites. In contrast previous reports, which chalcogens were solely involved Lewis acidic activation, our mechanistic investigation unraveled that often neglected flanking aromatic substituents phosphonoselenides can substantially contribute catalysis engaging π-interactions. Computations NMR spectroscopy indicated chalcogenic components catalyst be collectively exploited foster conformational distortion glycal away from usual half-chair boat conformation, liberates convex β-face nucleophilic attack.

Язык: Английский

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Zirconaaziridine-Mediated Ni-Catalyzed Diastereoselective C(sp²)-Glycosylation

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(24), С. 16753 - 16763

Опубликована: Июнь 11, 2024

In the realm of organic synthesis, catalytic and stereoselective formation C-glycosidic bonds is a pivotal process, bridging carbohydrates with aglycones. However, inherent chirality saccharide scaffold often has substantial impact on stereoinduction imposed by chiral ligand. this study, we have established an unprecedented zirconaaziridine-mediated asymmetric nickel catalysis, enabling diastereoselective coupling bench-stable glycosyl phosphates range (hetero)aromatic glycal iodides as feasible electrophiles. Our developed method showcases broad scope high tolerance for various functional groups. More importantly, precise stereocontrol toward both anomeric configurations forming C(sp2)-glycosides can be realized simply utilizing popular bioxazoline (biOx) ligands in reductive Ni catalysis. Regarding operating mechanism, experimental computational studies support occurrence redox transmetalation leading to transient, bimetallic Ni–Zr species that acts potent efficient single-electron reductant process.

Язык: Английский

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Synthesis of 2-Indolyl C-Glycoside Neopetrosins A and C and Congeners via Ni-Catalyzed Photoreductive Cross-Coupling

Organic Letters, Год журнала: 2023, Номер 25(36), С. 6741 - 6745

Опубликована: Авг. 30, 2023

The synthesis of neopetrosins A and C, two 2-indolyl C-α-d-mannopyranosides, their congeners has been realized via a direct Ni/photoredox-catalyzed reductive coupling 3-methoxycarbonyl-2-iodo-1H-indoles with pyranosyl bromides.

Язык: Английский

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

ACS Catalysis, Год журнала: 2024, Номер 14(15), С. 11532 - 11544

Опубликована: Июль 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.

Язык: Английский

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Stereoselective Construction of Multifunctional C-Glycosides Enabled by Nickel-Catalyzed Tandem Borylation/Glycosylation

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(32), С. 22413 - 22423

Опубликована: Авг. 3, 2024

Stereochemically pure saccharides have indispensable roles in fields ranging from medicinal chemistry to materials science and organic synthesis. However, the development of a simple, stereoselective, efficient glycosylation protocol access α- β-C-glycosides (particularly 2-deoxy entities) remains persistent challenge. Existing studies primarily focused on C1 modification carbohydrates transformation glycosyl radical precursors. Here, we innovate by harnessing situ generated glycosyl-Ni species achieve one-pot borylation cascade manner, which is enabled an earth-abundant nickel-catalyzed carboboration readily accessible glycals without any ligand. This work reveals potential for modular multifunctional platform facilitate simultaneous introduction C-C C-B bonds at stereogenic center saccharides, largely unexploited research area. Preliminary experimental computational indicate that endocyclic O C3 group play important stereoseclectively forging glycosidic bonds. As result, diverse range C-R (R = alkyl, aryl, alkenyl) 2-deoxygenated glycosides bearing modifiable boron groups could be rapidly made with excellent stereocontrol exhibit remarkable functional tolerance. The synthetic underscored late-stage natural products commercial drugs as well facile preparation various rare sugars, bioactive conjugates, key intermediates prorocentin, phomonol, aspergillide A.

Язык: Английский

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Direct Construction of C‐Alkyl Glycosides from Non‐Activated Olefins via Nickel‐Catalyzed C(sp³)─C(sp³) Coupling Reaction

Advanced Science, Год журнала: 2024, Номер 11(12)

Опубликована: Янв. 18, 2024

Among C-glycosides, C-alkyl glycosides are significant building blocks for natural products and glycopeptides. However, research on efficient construction methods remains relatively limited. Compared with Michael acceptors, non-activated olefins more challenging substrates have rarely been employed in the of C-glycosides. Here, a highly convenient approach synthesis through nickel-catalyzed C(sp

Язык: Английский

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Nickel and Chiral Phosphoric Acid Cocatalysis Enables Synthesis of C-Acyl Glycosides

Organic Letters, Год журнала: 2024, Номер 26(7), С. 1332 - 1337

Опубликована: Фев. 8, 2024

We disclosed a Ni/CPA cocatalyzed protocol to access diverse C-acyl glycosides under mild conditions with broad functional group compatibility through the coupling of readily available glycosyl bromides and carboxylic esters. The potential application methodology was demonstrated by glycosylation bioactive molecules transformation products variety value-added molecules. Mechanistic studies revealed that CPA might serve as bifunctional H-bond catalyst activate esters nickel catalyst.

Язык: Английский

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