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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Direct radical functionalization of native sugars

Nature, Год журнала: 2024, Номер 631(8020), С. 319 - 327

Опубликована: Июнь 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.

Язык: Английский

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Transformations of carbohydrate derivatives enabled by photocatalysis and visible light photochemistry

Chemical Science, Год журнала: 2024, Номер 15(4), С. 1204 - 1236

Опубликована: Янв. 1, 2024

This review article highlights the diverse ways in which recent developments areas of photocatalysis and visible light photochemistry are impacting synthetic carbohydrate chemistry.

Язык: Английский

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

Nature Synthesis, Год журнала: 2024, Номер 3(5), С. 623 - 632

Опубликована: Март 1, 2024

Язык: 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, Год журнала: 2024, Номер 146(8), С. 5502 - 5510

Опубликована: Фев. 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.

Язык: Английский

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Dehydroxylative radical N-glycosylation of heterocycles with 1-hydroxycarbohydrates enabled by copper metallaphotoredox catalysis

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Апрель 22, 2024

Abstract N-Glycosylated heterocycles play important roles in biological systems and drug development. The synthesis of these compounds heavily relies on ionic N-glycosylation, which is usually constrained by factors such as labile glycosyl donors, precious metal catalysts, stringent conditions. Herein, we report a dehydroxylative radical method for synthesizing N -glycosides leveraging copper metallaphotoredox catalysis, stable readily available 1-hydroxy carbohydrates are activated direct N-glycosylation. Our employs inexpensive photo- copper- catalysts can tolerate some extent water. reaction exhibits broad substrate scope, encompassing 76 examples, demonstrates high stereoselectivity, favoring 1,2- trans selectivity furanoses α-selectivity pyranoses. It also site-selectivity substrates containing multiple N-atoms. synthetic utility showcased through the late-stage functionalization bioactive pharmaceuticals like Olaparib, Axitinib, Metaxalone. Mechanistic studies prove presence radicals importance catalysis.

Язык: Английский

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Generation and Use of Glycosyl Radicals under Acidic Conditions: Glycosyl Sulfinates as Precursors

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(16)

Опубликована: Фев. 10, 2023

We herein report a method that enables the generation of glycosyl radicals under highly acidic conditions. Key to success is design and use sulfinates as radical precursors, which are bench-stable solids can be readily prepared from commercial starting materials. This development allows installation units onto pyridine rings directly by Minisci reaction. further demonstrate utility this in late-stage modification complex drug molecules, including anticancer agent camptothecin. Experimental studies provide insight into reaction mechanism.

Язык: Английский

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C‐GlycosideSynthesis Enabled by Nickel Catalysis

Chinese Journal of Chemistry, Год журнала: 2023, Номер 41(17), С. 2217 - 2236

Опубликована: Апрель 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.

Язык: Английский

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Recent Advances in First-Row Transition Metal-Catalyzed Reductive Coupling Reactions for π-Bond Functionalization and C-Glycosylation

Accounts of Chemical Research, Год журнала: 2023, Номер 56(22), С. 3292 - 3312

Опубликована: Ноя. 2, 2023

ConspectusEfficient construction of ubiquitous carbon-carbon bonds between two electrophiles has garnered interest in recent decades, particularly if it is mediated by nonprecious, first-row transition metals. Reductive coupling advantages over traditional cross-coupling obviating the need for stoichiometric air- and moisture-sensitive organometallic reagents. By harnessing metal-catalyzed reductive as a powerful tool, intricate molecular architectures can be readily assembled through installation C-C across π systems (alkenes/alkynes) via reaction with appropriate electrophiles. Despite advances alkene difunctionalization, there remains significant potential discovery novel pathways. In this regard, development protocols that enable union challenging alkyl/alkynyl high regio- chemoselectivity highly sought-after goal.Apart from π-bond functionalization, found application carbohydrate chemistry, synthesis valuable C-glycosyl compounds. vein, suitable glycosyl donors used to generate reactive radical intermediates under conditions. Through elaborately designed reactions, these trapped furnish pharmaceutically relevant glycoconjugates. Consequently, diversification compound using metal catalysis holds strong appeal.In Account, we summarize our efforts reactions applications alkene/alkyne functionalization C-glycosylation. We will first discuss nickel (Ni)-catalyzed difunctionalization alkenes, aided an 8-aminoquinoline (AQ) directing auxiliary. Next, highlight Ni-catalyzed hydroalkylation alkenyl amides tethered similar AQ-derived Lastly, efficient 1,3-enynes involving site- stereoselective terminal alkynes alkynyl halides NHPI esters.Beyond dicarbofunctionalization, extended paradigm toward C-glycosidic linkages carbohydrates. employing earth-abundant iron (Fe)-based catalyst, show useful radicals generated chlorides These captured bond formation C-aryl, C-alkenyl, C-alkynyl compounds diastereoselectivity. Our multicomponent chlorides, aryl/alkyl iodides, isobutyl chloroformate conditions led C-acyl glycosides. addition Fe Ni, discovered Ti-catalyzed/Mn-promoted synthetic route access C-alkyl C-alkenyl compounds, electron-deficient alkenes/alkynes. further developed electron donor-acceptor (EDA) photoactivation system leveraging decarboxylative deaminative strategies C-glycosylation Ni catalysis. This approach been demonstrated selectively activate carboxyl amino motifs glycopeptide conjugates. Finally, distinct catalytic transformations bench-stable heteroaryl sulfones, achieved stereodivergent both α- β-anomers C-aryl glycosides, one which involves aryl iodides.The findings presented Account are anticipated have far-reaching implications beyond research. foresee results pave way new founded on concept coupling, leading future.

Язык: Английский

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Photoredox-catalyzed protecting-group-free C-glycosylation with glycosyl sulfinate via the Giese reaction

Chemical Communications, Год журнала: 2023, Номер 59(55), С. 8564 - 8567

Опубликована: Янв. 1, 2023

C-Glycoside analogs of naturally occurring glycoconjugates are useful tools for chemical biology studies, but their synthesis usually requires protection the hydroxyl groups glycosyl donors. Here we report protecting-group-free and photoredox-catalyzed C-glycosylation with sulfinates Michael acceptors via Giese radical addition.

Язык: Английский

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