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

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

4-Methylphenyl 2,3-di-O-benzoyl-4-O-benzyl-6-O-(9-fluorenylmethoxycarbonyl)-1-thio-β-D-glucopyranoside is a synthetically modified thioglycoside derivative designed for controlled glycosylation reactions in carbohydrate chemistry. This compound features a glucose backbone (β-D-glucopyranoside) with multiple protective groups strategically placed to enable selective reactivity during oligosaccharide synthesis.

Structural Features

Core structure:

• A β-D-glucopyranose ring with a sulfur atom replacing the anomeric oxygen, forming a 1-thio linkage to a 4-methylphenyl group.

Protective groups:

1. 2- and 3-positions: Benzoyl esters (electron-withdrawing groups that stabilize against acid hydrolysis)
2. 4-position: Benzyl ether (acid-stable, removable via hydrogenolysis)
3. 6-position: 9-Fluorenylmethoxycarbonyl (Fmoc) group – a base-labile protecting group allowing selective deprotection under mild piperidine treatment

Key Properties

Synthetic Utility

• Glycosyl donor: The thioglycoside moiety acts as a leaving group, enabling glycosidic bond formation under thiophilic activation (e.g., NIS/TfOH).
• Orthogonal protection: Combination of benzoyl (acid-stable), benzyl (hydrogenolysis-sensitive), and Fmoc (base-labile) groups allows sequential deprotection for stepwise synthesis.
• Compatibility: Used in automated oligosaccharide synthesis due to Fmoc’s compatibility with solid-phase techniques.

Applications

• Neoglycoconjugate synthesis: Fmoc removal exposes C6-OH for subsequent conjugation to proteins/peptides.
• Glycosidase inhibitor development: Protected glucose derivatives serve as transition-state analogs in enzyme inhibition studies.
• Dendrimer construction: Enables controlled branching through selective deprotection at C6.

The compound’s synthesis typically involves:

1. Thioglycoside formation via BF₃·OEt₂-catalyzed coupling of per-O-acetyl-glucose with 4-methylthiophenol.
2. Sequential protection using benzylidene acetal (C4/C6), followed by regioselective benzoylation (C2/C3).
3. Fmoc introduction at C6 through carbodiimide-mediated coupling after benzylidene ring-opening.

This derivative exemplifies modern carbohydrate engineering strategies that combine traditional protecting groups with photolabile/base-sensitive groups for precision synthesis.

Citations:

1. https://pubmed.ncbi.nlm.nih.gov/8135348/
2. https://pubchem.ncbi.nlm.nih.gov/compound/1326804-93-6
3. https://www.rsc.org/suppdata/c8/sc/c8sc01743c/c8sc01743c1.pdf
4. https://pubchem.ncbi.nlm.nih.gov/compound/10411640
5. https://glycomindsynth.com/product_detail/517/Monosaccharide
6. https://www.bocsci.com/product/4-methylphenyl-2-o-benzoyl-3-4-di-o-benzyl-6-o-9-fluorenylmethoxycarbonyl-339431.html
7. https://synthose.com/products/ML822
8. https://glycodepot.com/product/4-methylphenyl-2-o-benzoyl-36-di-o-benzyl-4-o-9-fluorenylmethoxycarbonyl-1-thio-%CE%B2-d-glucopyranoside/