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

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(15), P. 11532 - 11544

Published: July 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.

Language: Английский

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Polarity-Matched Initiation of Radical-Polar Crossover Reactions for the Synthesis of C-Allyl Glycosides with gem-Difluoroalkene Groups

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(14), P. 10175 - 10179

Published: July 8, 2024

Herein, we disclose a general method for the assembly of

Language: Английский

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One‐Pot Hetero‐Di‐C‐Glycosylation of the Natural Polyphenol Phloretin by a Single C‐Glycosyltransferase With Broad Sugar Substrate Specificity

Biotechnology and Bioengineering, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

The structural motif of hetero-di-C-glycosyl compound is prominent in plant polyphenol natural products and involves two different glycosyl residues (e.g., β-d-glucosyl, β-d-xylosyl) attached to carbons the same phenolic ring. Polyphenol hetero-di-C-glycosides attract attention as specialized ingredients herbal medicines their tailored synthesis by enzymatic C-glycosylation promising overcome limitations low availability expand molecular diversity new-to-nature glycoside structures. However, installing these di-C-glycoside structures with synthetic precision efficiency challenging. Here we have characterized syntheses C-β-galactosyl-C-β-glucosyl C-β-glucosyl-C-β-xylosyl on phloroglucinol ring phloretin, using kumquat (Fortunella crassifolia) C-glycosyltransferase (FcCGT). FcCGT uses uridine 5'-diphosphate (UDP)-galactose (5 mU/mg) UDP-xylose (0.3 U/mg) at lower activity than UDP-glucose (3 U/mg). 3'-C-β-glucoside (nothofagin) ~10-fold less reactive non-glycosylated phloretin all UDP-sugars, suggesting practical order hetero-di-C-glycosylation C-galactosylation or C-xylosylation followed C-glucosylation resulting mono-C-glycoside. Each performed presence twofold excess UDP-sugar proceeds completion appears be effectively irreversible, evidenced absence residue exchange extended reaction times. Synthesis shown 10 mM concentration quantitative conversion cascade synthase, allowing for situ formation from more expedient donor substrate UDP-glucuronic acid. desired Xyl Gal was obtained a single product its structure confirmed NMR.

Language: Английский

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Lewis Acid-Mediated Domino Glycosylation/Cyclization of Substituted Glycals: A Stereoselective Route Toward the Synthesis of 1,2-Annulated C-Glycosides

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

Published: March 14, 2025

Annulated C-glycosides are widely recognized for their natural abundance and diverse bioactivity. Traditional synthesis emphasizes stereoselective α/β C-glycoside formation, but efficiently engaging both reactive carbons of glycosyl donors remains challenging. This study introduces a novel domino sequence using substituted glycals β-naphthols under Lewis acid catalysis, generating glycosylated intermediates that undergo cascade reactions to yield annulated 1,2-C-glycosides. The method features broad substrate scope, mild conditions, versatility. Notably, annulation type varies with glycals, yielding [3 + 2] or 3] fused pyran systems. Control experiments DFT calculations provide mechanistic insights into substrate-specific product formation.

Language: Английский

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The Liebeskind–Srogl Cross-Coupling Reaction Towards the Synthesis of Biologically Active Compounds

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 117526 - 117526

Published: March 1, 2025

Language: Английский

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Arene Substitutions in Orchid Bibenzyls: Mechanistic Insights into Glucose Uptake and Lipid Metabolism for Targeting Metabolic Disorders

Nutrients, Journal Year: 2025, Volume and Issue: 17(7), P. 1104 - 1104

Published: March 21, 2025

Phytochemicals possess diverse therapeutic potential; however, the impact of arene substitutions on pharmacological properties bibenzyl compounds batatasin III and gigantol, derived from Dendrobium venustum, remains unexplored. This study examines how structural differences between these affect cellular glucose uptake lipid metabolism during adipocyte differentiation. The effects both cytotoxicity were assessed in mouse human pre-adipocytes rat skeletal muscle myoblasts using colorimetric assays. Lipid was evaluated through Oil Red O staining quantification triglyceride glycerol levels, while protein gene expression differentiation analyzed via western blotting RT-qPCR. At highest non-cytotoxic concentration (25 µM), gigantol significantly enhanced (up to 2-fold) under basal insulin-stimulated conditions, whereas showed a similar effect only conditions. Gigantol upregulated GLUT1 GLUT4 myotubes but downregulated them adipocytes, had minimal transporters. Both suppressed accumulation adipocytes by decreasing intracellular content promoting extracellular release. However, did not release early differentiation, as evidenced marked downregulation key lipogenic proteins (PLIN1, LPL, FABP4) observed with gigantol. Molecular docking analyses suggest that gigantol's greater bioactivity may result its higher number substitutions. provides first evidence among orchid-derived bibenzyls influence their properties. Our findings support strategic modification natural products potential approach for managing metabolic disorders.

Language: Английский

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Recent Advances in the Synthesis of SGLT2 Inhibitors and Natural Products from Carbohydrates

Carbohydrate Research, Journal Year: 2025, Volume and Issue: unknown, P. 109477 - 109477

Published: April 1, 2025

Language: Английский

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Transient imine as a directing group for the Pd-catalyzed anomeric C(sp³)–H arylation of 3-aminosugars

Chemical Communications, Journal Year: 2023, Volume and Issue: 59(17), P. 2497 - 2500

Published: Jan. 1, 2023

The first example of Pd( ii )-catalyzed anomeric C(sp 3 )–H arylation 3-aminosugars by using a transient directing group approach is reported. free amine was then exploited in CuAAC reaction to access variety C3-triazolo C -glycosides good yields.

Language: Английский

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Reaction intensification for biocatalytic production of polyphenolic natural product di‐C‐β‐glucosides

Biotechnology and Bioengineering, Journal Year: 2023, Volume and Issue: 120(6), P. 1506 - 1520

Published: Feb. 15, 2023

Polyphenolic aglycones featuring two sugars individually attached via C-glycosidic linkage (di-C-glycosides) represent a rare class of plant natural products with unique physicochemical properties and biological activities. Natural scarcity such di-C-glycosides limits their use-inspired exploration as pharmaceutical ingredients. Here, we show biocatalytic process technology for reaction-intensified production the di-C-β-glucosides representative phenol substrates, phloretin (a flavonoid) phenyl-trihydroxyacetophenone phenolic synthon synthesis), from sucrose. The synthesis proceeds an iterative two-fold C-glycosylation respective aglycone, supplied inclusion complex 2-hydroxypropyl β-cyclodextrin enhanced water solubility up to 50 mmol/L, catalyzed by kumquat di-C-glycosyltransferase (di-CGT), it uses UDP-Glc provided in situ sucrose soybean synthase, catalytic amounts (≤3 mol%) UDP added. Time course analysis reveals second rate-limiting (0.4-0.5 mmol/L/min) di-C-glucoside production. With internal supply keeping at constant steady-state concentration (≥50% added) during reaction, di-C-glycosylation is driven completion (≥95% yield). Contrary mono-C-glucoside intermediate which stable, requires addition reducing agent (10 mmol/L 2-mercaptoethanol) prevent its decomposition synthesis. Both di-C-glucosides are isolated reaction mixtures excellent purity (≥95%), expected structures confirmed NMR. Collectively, this study demonstrates efficient glycosyltransferase cascade flexible use product di-C-β-glucoside expedient substrates.

Language: Английский

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Recent Advances on the Synthesis of C-Glycosides from 1,2-Glycals

Synthesis, Journal Year: 2023, Volume and Issue: 56(07), P. 1070 - 1096

Published: Dec. 5, 2023

Abstract The development of stereoselective synthetic routes for C-glycosides has attracted immense attention from carbohydrate chemists over the last two decades. In this short review, progress made decade towards synthesis using glycals as precursors is discussed. Glycals have been extensively manipulated to generate oxocarbenium cations or glycosyl anions formation C–C bonds at anomeric position through attack C-nucleophiles via transition-metal-catalyzed coupling reactions. Recent reports on carbon-Ferrier, intramolecular Cope, and Claisen rearrangements, along with various reactions in presence absence directing groups are evaluated herein. Contemporary applications these syntheses natural products, drugs scaffolds bioactive potential briefly 1 Introduction 2 Rearrangement Reactions 2.1 Carbon-Ferrier 2.2 Other 3 C1 Coupling 4 Annulations 5 Addition 6 Natural Product Synthesis 7 Conclusion

Language: Английский

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