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

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

Ethyl 3,6-di-O-benzoyl-2-O-benzyl-4-O-(9-fluorenylmethoxycarbonyl)-1-thio-β-D-glucopyranoside is a strategically engineered thioglycoside designed for controlled oligosaccharide synthesis. It combines orthogonal protecting groups to enable sequential deprotection and precise glycosylation control in complex carbohydrate assembly.

Structural Features

Core framework:

• β-D-glucopyranose ring with an ethylthio group at the anomeric position (C1), forming a thioglycoside donor activatable by thiophilic promoters (e.g., NIS/TfOH).

Orthogonal protecting groups:

Key Properties

• Molecular formula: C₄₈H₄₄O₉S (estimated)
• Molecular weight: ~820.0 g/mol
• Reactivity:
  • Benzoyl esters at C3/C6 withdraw electron density, moderating glycosyl donor reactivity.
  • Fmoc at C4 enables compatibility with solid-phase synthesis workflows.

Synthetic Utility

1. Sequential Deprotection:
   • Step 1: Fmoc removal (C4) under mild basic conditions (e.g., piperidine/DMF).
   • Step 2: Benzoyl cleavage (C3/C6) via alkaline hydrolysis.
   • Step 3: Benzyl deprotection (C2) via hydrogenolysis.
2. Glycosylation Control:
   • The ethylthio group at C1 facilitates efficient activation for glycosidic bond formation.
   • Benzyl protection at C2 provides steric shielding to direct regioselective coupling.
3. Functionalization Flexibility:
   • Exposed C4-OH after Fmoc removal allows site-specific modifications (e.g., conjugation to peptides or solid supports).

Applications

• Glycoconjugate vaccines: Selective functionalization at C4 for antigen attachment.
• Oligosaccharide libraries: Orthogonal deprotection enables modular assembly of branched glycans.
• Enzyme substrate analogs: Protected glucose scaffold for glycosidase inhibition studies.

Stability Profile

This compound exemplifies advanced carbohydrate engineering, integrating traditional protecting groups (benzyl, benzoyl) with modern orthogonal motifs (Fmoc) for precision synthesis of complex glycans. Its design supports both solution-phase and automated solid-phase methodologies, making it a versatile tool in glycobiology and medicinal 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://europepmc.org/article/pmc/6531329
5. https://pubs.rsc.org/en/content/getauthorversionpdf/c9ob00573k
6. https://pmc.ncbi.nlm.nih.gov/articles/PMC6259426/
7. https://pmc.ncbi.nlm.nih.gov/articles/PMC2952681/
8. https://onlinelibrary.wiley.com/doi/abs/10.1002/asia.201901621