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

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

Ethyl 2-O-benzoyl-4,6-di-O-benzyl-3-O-(9-fluorenylmethoxycarbonyl)-1-thio-β-D-glucopyranoside is a thioglycoside derivative designed for advanced glycosylation reactions in carbohydrate synthesis. It features a carefully chosen set of orthogonal protecting groups, enabling selective deprotection and precise regioselective glycosylation.

Structural Features

1. Core Structure:
   • A β-D-glucopyranoside scaffold with an ethylthio (–SEt) group at the anomeric (C1) position, serving 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 & C6: Benzyl ethers (–OBn)
     • Acid-stable and removable via hydrogenolysis, compatible with Fmoc and benzoyl groups.

Synthetic Utility

• Orthogonal Deprotection Strategy:
  • Sequential removal of protecting groups allows 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).
  • 13C^13 \text{C}13C NMR confirms the presence of carbonyls (~167 ppm for benzoyl) and aromatic carbons from the benzyl and Fmoc groups.
• Mass Spectrometry:
  • ESI-MS confirms molecular weight (expected [M+Na]⁺ ~800–900 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://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/