4-methylphenyl 2-deoxy-2-[(2,2,2,-trichloroacetyl)amino]-3-O-(9- fluorenylmethoxycarbonyl)-4-O-benzyl-6-O-levulinoyl-1-thio-β-Dgalactopyranoside

4-Methylphenyl 2-deoxy-2-[(2,2,2-trichloroacetyl)amino]-3-O-(9-fluorenylmethoxycarbonyl)-4-O-benzyl-6-O-levulinoyl-1-thio-β-D-galactopyranoside

4-Methylphenyl 2-deoxy-2-[(2,2,2-trichloroacetyl)amino]-3-O-(9-fluorenylmethoxycarbonyl)-4-O-benzyl-6-O-levulinoyl-1-thio-β-D-galactopyranoside is a synthetic thioglycoside derivative designed for advanced carbohydrate chemistry applications. This compound integrates multiple protecting groups to enable controlled reactivity during oligosaccharide synthesis.

Chemical Structure

The molecule is based on a β-D-galactopyranoside scaffold with the following modifications:

• 1-Thio-4-methylphenyl group: Replaces the anomeric oxygen, forming a thioglycoside linkage that enhances stability and serves as a glycosyl donor in synthetic reactions.
• 2-Deoxy-2-[(2,2,2-trichloroacetyl)amino] group: A 2-amino sugar derivative protected by a trichloroacetyl (TCA) group, which is acid-stable and removable via mild hydrolysis (e.g., Zn/AcOH).
• 3-O-Fmoc group: A 9-fluorenylmethoxycarbonyl (Fmoc) carbonate at position 3, acting as a temporary protecting group cleavable under basic conditions (e.g., piperidine).
• 4-O-benzyl group: A permanent benzyl ether protection at position 4, providing stability under acidic/basic conditions and enabling selective deprotection later.
• 6-O-levulinoyl group: A levulinoyl ester at position 6, acting as a temporary protecting group that can be cleaved under mild conditions.

Key Properties

• Molecular formula: Estimated based on analogous structures, likely around C34H35Cl3NO9S\text{C}_{34}\text{H}_{35}\text{Cl}_3\text{NO}_9\text{S}C34H35Cl3NO9S.
• Stereochemistry: β-configuration at the anomeric center (C1), critical for mimicking biological glycosylation patterns.
• Role in synthesis:
  • The thioglycoside moiety facilitates activation via thiophilic promoters (e.g., NIS/TfOH) for glycosylation reactions.
  • Benzyl group ensures regioselective reactivity, while Fmoc allows orthogonal deprotection for sequential glycosylation.
  • TCA group protects the amino group during glycosylation steps, preventing side reactions.

Applications

This compound is used in solid-phase oligosaccharide synthesis to build complex glycans. Its design supports iterative coupling cycles, where the Fmoc group is selectively removed to expose the 3-OH for subsequent glycosylation. The TCA group remains intact during these steps, enabling late-stage functionalization of the amino group. Thioglycosides like this derivative are also explored as metabolic decoys to inhibit glycosylation processes.

Synthetic Considerations

• Preparation: Likely synthesized via sequential protection:
  1. Trichloroacetylation of the 2-amino group.
  2. Fmoc protection at position 3.
  3. Benzylation at position 4.
  4. Levulinoylation at position 6.
  5. Thioglycoside formation at the anomeric position, which can be achieved using efficient methods like triflic acid-mediated synthesis.
• Stability: Stable under standard glycosylation conditions but sensitive to conditions that cleave the Fmoc or levulinoyl groups.

This multifunctional building block exemplifies advanced strategies in glycochemistry, balancing stability and orthogonality for automated glycan assembly.

Citations:

1. https://pubchem.ncbi.nlm.nih.gov/compound/4-Methylumbelliferyl-alpha-D-galactopyranoside
2. https://www.thermofisher.in/chemicals/shop/products/4-methylphenyl-2-3-4-6-tetra-o-acetyl-beta-d-thiogalactopyranoside-thermo-scientific/ALF-J66025-03
3. https://pubchem.ncbi.nlm.nih.gov/compound/Methyl-alpha-D-galactopyranoside
4. https://patents.google.com/patent/WO2021038068A1/en
5. https://www.medchemexpress.com/4-methylphenyl-tetra-o-acetyl-%CE%B2-d-galactopyranoside.html
6. https://www.sigmaaldrich.com/IN/en/product/sigma/m1379
7. https://www.fishersci.fi/shop/products/4-methylphenyl-2-3-4-6-tetra-o-acetyl-beta-d-thiogalactopyranoside/p-7043183