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

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

Ethyl 3,4,6-tri-O-benzyl-2-O-(9-fluorenylmethoxycarbonyl)-1-thio-β-D-glucopyranoside is a thioglycoside derivative designed for advanced glycosylation reactions in carbohydrate chemistry. Its structure incorporates orthogonal protecting groups to enable precise regioselective deprotection and stereoselective coupling, making it highly suitable for oligosaccharide synthesis.

Structural Features

1. Core Structure:
   • A β-D-glucopyranoside scaffold with an ethylthio (–SEt) group at the anomeric (C1) position, acting as a thioglycosyl donor for activation under mild conditions (e.g., NIS/AgOTf).
2. Protecting Groups:
   • C2: 9-Fluorenylmethoxycarbonyl (Fmoc)
     • Base-labile (e.g., cleaved by piperidine/DMF), enabling selective removal in solid-phase synthesis workflows.
   • C3, C4, C6: Benzyl ethers (–OBn)
     • Acid-stable and removable via hydrogenolysis (H₂/Pd-C), offering compatibility with Fmoc and other base-sensitive groups.

Synthetic Utility

• Orthogonal Deprotection Strategy:
  • Fmoc removal exposes the C2 hydroxyl group for regioselective glycosylation.
  • Benzyl ethers can be removed globally via hydrogenolysis after completing glycan assembly.
• Reactivity Control:
  • The ethylthio group facilitates activation under mild thiophilic conditions, ensuring compatibility with sensitive functional groups.
  • Benzyl protection stabilizes the molecule during acidic or oxidative steps in synthesis.

Characterization

• NMR Spectroscopy:
  • 1H^1 \text{H}1H NMR shows aromatic signals for benzyl and Fmoc groups (~7.2–7.8 ppm).
  • 13C^13 \text{C}13C NMR confirms the benzyl carbons (~138–140 ppm) and Fmoc carbonyl (~155–160 ppm).
• Mass Spectrometry:
  • ESI-MS validates molecular weight (expected [M+Na]⁺ ~700–750 Da).

Applications

• Oligosaccharide Synthesis: Ideal for constructing complex glycans with regioselective glycosylation steps.
• Solid-Phase Glycan Assembly: Fmoc compatibility supports automated synthesis of glycoconjugates.

This compound exemplifies the utility of orthogonal protecting groups in carbohydrate chemistry, enabling precise control over reactivity and deprotection for complex glycan construction.

Citations:

1. https://patents.google.com/patent/WO2000042057A1/en
2. https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2023.1332837/full
3. https://pubmed.ncbi.nlm.nih.gov/31895493/
4. https://pmc.ncbi.nlm.nih.gov/articles/PMC10808579/
5. https://europepmc.org/article/pmc/6531329
6. https://pubs.rsc.org/en/content/getauthorversionpdf/c9ob00573k
7. https://pmc.ncbi.nlm.nih.gov/articles/PMC6259426/
8. https://pmc.ncbi.nlm.nih.gov/articles/PMC2952681/