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

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

Ethyl 2-O-benzoyl-4-O-benzyl-3-O-(9-fluorenylmethoxycarbonyl)-6-O-levulinoyl-1-thio-β-D-glucopyranoside is a thioglycoside derivative designed for precise glycosylation in carbohydrate synthesis. It features a carefully selected set of orthogonal protecting groups that enable regioselective deprotection and stereocontrol during complex oligosaccharide assembly.

Structural Features

1. Core Structure:
   • A β-D-glucopyranoside scaffold with an ethylthio (–SEt) group at the anomeric (C1) position, acting as a glycosyl donor for activation under mild thiophilic conditions (e.g., NIS/AgOTf).
2. Protecting Groups:
   • C2: Benzoyl ester (–OBez)
     • Provides anchimeric assistance for β-selectivity during glycosylation and is removable under mild acidic or basic conditions.
   • C3: 9-Fluorenylmethoxycarbonyl (Fmoc)
     • Base-labile, allowing selective removal with piperidine/DMF in solid-phase synthesis workflows.
   • C4: Benzyl ether (–OBn)
     • Acid-stable and removable via hydrogenolysis, compatible with Fmoc and levulinoyl groups.
   • C6: Levulinoyl ester (–OLv)
     • Base-sensitive and selectively removable under hydrazine-based conditions without affecting other groups.

Synthetic Utility

• Orthogonal Deprotection Strategy:
  • Sequential removal of protecting groups enables precise exposure of hydroxyl functionalities for regioselective glycosylation steps.
  • The benzoyl group at C2 ensures β-selectivity via neighboring group participation, while the ethylthio donor facilitates activation under mild conditions.
• Applications in Glycan Assembly:
  • Suitable for constructing linear or branched glycans requiring controlled glycosylation steps.
  • Fmoc compatibility supports automated solid-phase synthesis of glycoconjugates and glycomimetics.

Characterization

• NMR Spectroscopy:
  • 1H^1 \text{H}1H NMR reveals distinct aromatic signals for benzoyl, benzyl, and Fmoc groups (~7.1–7.8 ppm), along with levulinoyl carbonyl (~172 ppm in 13C^13 \text{C}13C NMR).
• Mass Spectrometry:
  • ESI-MS confirms molecular weight (expected [M+Na]⁺ ~800–850 Da).

Applications

This compound is widely used in advanced carbohydrate chemistry for synthesizing biologically relevant glycans and glycoconjugates. Its orthogonal protecting group strategy allows for precise regioselective deprotection, making it ideal for both solution-phase and solid-phase oligosaccharide synthesis.

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