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

Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 56(22), P. 3292 - 3312

Published: Nov. 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.

Language: Английский

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

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: April 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.

Language: Английский

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Nickel-catalyzed cross-electrophile coupling of unactivated (hetero)aryl sulfone with aryl bromide

Journal of Catalysis, Journal Year: 2024, Volume and Issue: 430, P. 115359 - 115359

Published: Feb. 1, 2024

Language: Английский

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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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Stereoretentive Conversion to C-Glycosides from S-Glycosides via Ligand-Coupling on Sulfur(IV)

Organic Letters, Journal Year: 2025, Volume and Issue: 27(4), P. 954 - 960

Published: Jan. 21, 2025

A novel strategy is reported for the stereoselective synthesis of C(sp2)-C(sp3) C-glycosides, which converts heteroaryl S-glycosides into C-glycosides with retention configuration through a sequential process involving oxidation and Grignard reagent attack. The new method involves generation S(IV) intermediate, followed by ligand coupling glycosyl groups to yield C-glycosides. diverse were achieved good efficiency.

Language: Английский

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

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(42)

Published: Aug. 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.

Language: 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, Journal Year: 2023, Volume and Issue: 63(7)

Published: Dec. 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.

Language: Английский

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