Ethyl 2-O-benzoyl-3-O-levulinoyl-4-O-(9-fluorenylmethoxycarbonyl)-6-O-benzyl-1-thio-beta-D-glucopyranoside

Ethyl 2-O-benzoyl-3-O-levulinoyl-4-O-(9-fluorenylmethoxycarbonyl)-6-O-benzyl-1-thio-β-D-glucopyranoside

Ethyl 2-O-benzoyl-3-O-levulinoyl-4-O-(9-fluorenylmethoxycarbonyl)-6-O-benzyl-1-thio-β-D-glucopyranoside is a thioglycoside derivative designed for precise glycosylation reactions in carbohydrate synthesis. Its structure incorporates multiple orthogonal protecting groups, enabling selective deprotection and stereocontrol during synthetic workflows.

Structural Features

1. Core Structure:
   • A β-D-glucopyranoside scaffold with an ethylthio group at the anomeric (C1) position, serving as a glycosyl donor for thiophilic activation in glycosylation reactions.
2. Protecting Groups:
   • C2: Benzoyl ester (–OBez), which participates via neighboring group participation (NGP) to enforce β-selectivity during glycosylation and is removable under mild acidic or basic conditions.
   • C3: Levulinoyl ester (–OLvl), a base-sensitive group allowing selective removal without affecting other protecting groups.
   • C4: 9-Fluorenylmethoxycarbonyl (Fmoc), a base-labile group commonly used in solid-phase synthesis workflows.
   • C6: Benzyl ether (–OBn), removable via hydrogenolysis, offering compatibility with acid-sensitive groups.

Synthetic Utility

• Orthogonal Deprotection Strategy:
  • Sequential removal of the protecting groups enables regioselective exposure of hydroxyl functionalities for controlled glycosylation steps.
  • The benzoyl group at C2 ensures β-selectivity via NGP, while the ethylthio donor facilitates activation under mild conditions using promoters like NIS/AgOTf.
• Applications in Glycan Assembly:
  • Ideal for synthesizing complex oligosaccharides with branched or sterically hindered structures.
  • Fmoc protection aligns with automated solid-phase synthesis, making it suitable for glycomimetic and glycopeptide production.

Characterization

• Analytical techniques such as 1H^1 \text{H}1H and 13C^13 \text{C}13C NMR confirm stereochemistry and substitution patterns, with specific downfield shifts indicating the presence of benzoyl and Fmoc groups.
• Mass spectrometry validates molecular weight, while IR spectroscopy confirms functional group presence.

Applications

This compound is widely used in advanced carbohydrate chemistry for stereoselective glycosylation, enabling the synthesis of biologically relevant glycans and glycomimetics critical for pharmaceutical and biochemical research.

Citations:

1. https://pmc.ncbi.nlm.nih.gov/articles/PMC6259426/
2. https://pmc.ncbi.nlm.nih.gov/articles/PMC8423405/
3. https://pmc.ncbi.nlm.nih.gov/articles/PMC9506437/
4. https://pubs.rsc.org/en/content/articlehtml/2023/ob/d3ob00817g
5. https://pubs.acs.org/doi/10.1021/ed074p1297
6. https://onlinelibrary.wiley.com/doi/10.1002/9783527697014.ch5
7. https://par.nsf.gov/servlets/purl/10157801
8. https://onlinelibrary.wiley.com/doi/abs/10.1002/9783527697014.ch3