Ethyl 2-O-benzoyl-4,6-O-benzylidene-3-O-(2-naphtylmethyl)-1-thio-β-D-glucopyranoside

Ethyl 2-O-benzoyl-4,6-O-benzylidene-3-O-(2-naphthylmethyl)-1-thio-β-D-glucopyranoside

Ethyl 2-O-benzoyl-4,6-O-benzylidene-3-O-(2-naphthylmethyl)-1-thio-β-D-glucopyranoside is a multifunctional thioglycoside designed for controlled reactivity in stereoselective glycosylation reactions. Its protective group arrangement balances electronic and steric effects, enabling precise chemoselective coupling in oligosaccharide synthesis.

Chemical Identity

• Molecular Formula: C₃₄H₃₄O₇S
• Molecular Weight: ~610.75 g/mol
• Key Features:
  • Thioethyl group at the anomeric position (enhanced stability and activation potential).
  • Benzoyl (electron-withdrawing) at O-2, benzylidene acetal (conformation-locking) at O-4/O-6, and 2-naphthylmethyl (bulky, electron-donating) at O-3.

Structural and Reactivity Insights

1. Protective Group Synergy:
   • 4,6-O-Benzylidene: Restricts the glucopyranoside ring to a rigid chair conformation, reducing unwanted side reactions.
   • 2-O-Benzoyl: Electron-withdrawing effect slightly disarms the donor but allows neighboring-group participation if activated.
   • 3-O-2-Naphthylmethyl: Bulky aromatic group increases steric hindrance on the β-face, potentially enhancing α-selectivity during glycosylation.
2. Reactivity Profile:
   • The thioethyl group enables activation under mild promoters (e.g., NIS/TfOH) while maintaining stability during storage.
   • Combined electronic effects (electron-withdrawing benzoyl vs. electron-donating naphthylmethyl) create a balanced “semiarmed” donor, suitable for chemoselective coupling with moderately reactive acceptors.

Applications

• Stereoselective Glycosylation: Used to construct α- or β-linked glycosides depending on promoter choice and acceptor reactivity. The 2-naphthylmethyl group may steer selectivity by hindering β-face nucleophilic attack.
• Intermediate in Oligosaccharide Synthesis: Strategic deprotection (e.g., acidic removal of benzylidene or basic hydrolysis of benzoyl) enables sequential functionalization.
• Chemoselective Strategies: Compatible with reactivity-based one-pot glycosylation methods due to intermediate donor reactivity.

Synthesis

Typical steps include:

1. Benzylidene acetal formation at O-4/O-6.
2. Benzoylation at O-2.
3. Naphthylmethyl ether installation at O-3 via alkylation.
4. Thioglycoside introduction at the anomeric center.

Physical Properties

• Solubility: Hydrophobic aromatic groups favor solubility in dichloromethane, chloroform, or THF.
• Stability: Crystalline solid with enhanced shelf-life due to thioglycoside and robust protective groups.

This compound exemplifies advanced protective group engineering in carbohydrate chemistry, offering tailored reactivity for synthesizing complex glycoconjugates and natural products.

Citations:

1. https://pmc.ncbi.nlm.nih.gov/articles/PMC5301963/
2. https://pmc.ncbi.nlm.nih.gov/articles/PMC2677192/
3. https://pmc.ncbi.nlm.nih.gov/articles/PMC2661424/
4. https://onlinelibrary.wiley.com/doi/10.1002/9783527618255.ch4
5. https://pubs.rsc.org/en/content/articlehtml/2023/ob/d3ob00817g
6. https://pmc.ncbi.nlm.nih.gov/articles/PMC11370891/
7. https://onlinelibrary.wiley.com/doi/abs/10.1002/9783527697014.ch3
8. https://onlinelibrary.wiley.com/doi/10.1002/ajoc.201900397