Harnessing Multistep Chalcogen Bonding Activation in the α-Stereoselective Synthesis of Iminoglycosides

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(15), P. 10608 - 10620

Published: April 2, 2024

The use of noncovalent interactions (NCIs) has received significant attention as a pivotal synthetic handle. Recently, the exploitation unconventional NCIs gained considerable traction in challenging reaction manifolds such glycosylation due to their capacity facilitate entry into difficult-to-access sugars and glycomimetics. While investigations involving oxacyclic pyrano- or furanoside scaffolds are relatively common, methods that allow selective synthesis biologically important iminosugars comparatively rare. Here, we report phosphonochalcogenide (PCH) catalyze stereoselective α-iminoglycosylation iminoglycals with wide array glycosyl acceptors remarkable protecting group tolerance. Mechanistic studies have illuminated counterintuitive role catalyst serially activating both donor acceptor up/downstream stages through chalcogen bonding (ChB). dynamic interaction chalcogens substrates opens up new mechanistic opportunities based on iterative ChB engagement disengagement multiple elementary steps.

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

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(24), P. 16753 - 16763

Published: June 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.

Language: Английский

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Total Synthesis of Nona-decasaccharide Motif from Ganoderma sinense Polysaccharide Enabled by Modular and One-Pot Stereoselective Glycosylation Strategy

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(25), P. 17446 - 17455

Published: June 11, 2024

Polysaccharides from a medicinal fungus Ganoderma sinense represent important and adjunctive therapeutic agents for treating various diseases, including leucopenia hematopoietic injury. However, the synthetic accessibility to long, branched, complicated carbohydrates chains polysaccharides remains challenging task in chemical synthesis. Here, we report modular synthesis of nona-decasaccharide motif polysaccharide GSPB70-S with diverse biological activities first time through one-pot stereoselective glycosylation strategy on basis glycosyl ortho-(1-phenyvinyl)benzoates, which not only sped up but also reduced waste avoided aglycones transfer issues inherent thioglycosides. The route highlights following key steps: (1) preactivation-based highly constructions several 1,2-cis-glycosidic linkages, three α-d-GlcN-(1 → 4) linkages one α-d-Gal-(1 bond via reagent N-methyl-N-phenylformamide modulation; (2) orthogonal assembly 1,2-trans-glycosidic linear branched glycans fragments by strategic combinations N-phenyltrifluoroacetimidates, ortho-alkynylbenzoates, ortho-(1-phenyvinyl)benzoates; (3) final [1 × 4 + 15] Yu efficient target. Additionally, shorter sequences 4-mer, 5-mer, 6-mer are prepared structure–activity relationship studies. present work shows that this can offer reliable effective means streamline complex many bonds.

Language: Английский

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β-Selective 2-Deoxy- and 2,6-Dideoxyglucosylations Catalyzed by Bis-Thioureas

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 30, 2024

We present methods for β-selective 2-deoxy- and 2,6-dideoxyglucosylations of natural products, carbohydrates, amino acids using bis-thiourea hydrogen-bond-donor catalysts. Disarming ester protecting groups were necessary to counter the high reactivity 2-deoxyglycosyl electrophiles toward non-stereospecific S

Language: Английский

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Palladium-Catalyzed Regio- and Stereoselective Glycosylation of Azole Heterocycles Enables Access to Diverse Heterocyclic N-Glycosides

Organic Letters, Journal Year: 2024, Volume and Issue: 26(32), P. 6878 - 6883

Published: Aug. 6, 2024

An efficient and practical glycosylation platform for synthesizing

Language: Английский

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Palladium-Catalyzed O-Glycosylation through π–π Interactions

Organic Letters, Journal Year: 2024, Volume and Issue: 26(25), P. 5396 - 5401

Published: June 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.

Language: Английский

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Palladium-Catalyzed Stereospecific Glycosylation Enables Divergent Synthesis of N–O-Linked Glycosides

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

Published: Jan. 9, 2025

We present a versatile palladium-catalyzed glycosylation platform that enables facile access to structurally diverse N-O-linked glycosides with constantly excellent regio- and stereoselectivities. Importantly, this approach offers broad substrate scope, low catalyst loadings, outstanding chemoselectivity, allowing for the selective reaction of oximes/hydroximic acids over hydroxyl groups would otherwise pose challenges in conventional methods. The synthetic utility method is further exemplified through range transformations late-stage modification bioactive molecules. Overall, our provides an efficient toolkit synthesis glycosides, which will facilitate their subsequent biological evaluations.

Language: Английский

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Insertion of Glycosylidene Carbenes into Phenolic O–H Bonds for the Synthesis of O-Aryl Glycosides

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 18, 2025

We present a new strategy for the synthesis of O-aryl glycosides through formal insertion glycosylidene carbenes into O–H bond phenols. The key carbene intermediates were generated in situ by copper-catalyzed oxidation bench-stable diaziridine precursors. This method enables glycosylation variety phenols with good yields, excellent diastereoselectivity, and chemoselectivity, providing highly practical late-stage complex natural products bioactive agents.

Language: Английский

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Stereoselective Approaches to β-Linked 2-Deoxy Sugars

Molecules, Journal Year: 2025, Volume and Issue: 30(7), P. 1578 - 1578

Published: April 1, 2025

This review presents a survey of recent developments in the synthesis β-linked 2-deoxy sugars. Approaches ranging from catalysis to de novo are described, with focus on methods developed last 10 years. Where relevant, application these technologies and mechanistic information is discussed. Finally, it concludes an examination scope limitations technologies, as well examinations about where field should head next.

Language: Английский

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