Ethyl 2-O-benzoyl-3,6-di-O-methyl-4-O-(9-fluorenylmethoxycarbonyl)-1-thio- β-D glucopyranoside

Ethyl 2-O-benzoyl-3,6-di-O-methyl-4-O-(9-fluorenylmethoxycarbonyl)-1-thio-β-D-glucopyranoside

Ethyl 2-O-benzoyl-3,6-di-O-methyl-4-O-(9-fluorenylmethoxycarbonyl)-1-thio-β-D-glucopyranoside is a strategically protected thioglycoside designed for controlled glycosylation in carbohydrate synthesis. Its architecture integrates orthogonal protecting groups to enable sequential deprotection and stereoselective coupling.

Structural Features

1. Core Scaffold:
   • β-D-glucopyranoside with an ethylthio (–SEt) group at the anomeric (C1) position, acting as a thioglycosyl donor activated by thiophilic promoters (e.g., NIS/AgOTf).
2. Protecting Groups:
   • C2: Benzoyl ester (–OBez)
     • Participates via neighboring group participation (NGP) to enforce β-selectivity during glycosylation. Removable under basic (e.g., NaOMe/MeOH) or acidic conditions.
   • C3/C6: Methyl ethers (–OMe)
     • Non-participating, electron-donating groups that stabilize the glycosyl intermediate and resist common deprotection conditions (e.g., acid/base).
   • C4: 9-Fluorenylmethoxycarbonyl (Fmoc)
     • Base-labile (e.g., piperidine/DMF), enabling selective removal in solid-phase synthesis workflows.

Synthetic Utility

• Orthogonal Deprotection:
  • Step 1: Fmoc cleavage (base) → exposes C4-OH for glycosylation.
  • Step 2: Benzoyl removal (base/acid) → unmask C2-OH for further coupling.
  • Step 3: Methyl groups remain intact until final global deprotection (e.g., strong acid).
• Reactivity Control:
  • Benzoyl at C2 ensures β-selectivity via NGP, while methyl ethers simplify regiochemical control by limiting undesired side reactions.

Characterization

• NMR:
  • 1H^1 \text{H}1H NMR shows distinct signals for Fmoc aromatic protons (7.1–7.8 ppm) and benzoyl carbonyl (~167 ppm in 13C^13 \text{C}13C NMR).
  • Methyl groups appear as singlets (~3.3–3.5 ppm).
• MS: ESI-MS confirms molecular weight (expected [M+Na]⁺ ~650–700 Da).

Applications

• Oligosaccharide Synthesis: Ideal for constructing linear or branched glycans requiring sequential glycosylation steps.
• Solid-Phase Platforms: Fmoc compatibility supports automated glycan assembly for therapeutic glycoconjugates
• Stability: Methyl ethers enhance stability during prolonged synthetic sequences compared to acid-labile groups.

This compound exemplifies the synergy of orthogonal protection (Fmoc, benzoyl, methyl) and stereochemical control, making it a versatile tool in synthetic carbohydrate chemistry.

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/