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

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

Ethyl 4,6-di-O-benzyl-2-deoxy-2-[(2,2,2-trichloroacetyl)amino]-3-O-(9-fluorenylmethoxycarbonyl)-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-Thioethyl group: Replaces the anomeric oxygen, forming a thioglycoside linkage that enhances stability and serves as a glycosyl donor in synthetic reactions. Thioglycosides are commonly synthesized using methods such as triflic acid-mediated reactions, which offer efficient synthesis pathways.
• 4,6-di-O-benzyl groups: Permanent benzyl ether protections at positions 4 and 6, providing stability under acidic/basic conditions and enabling selective deprotection later.
• 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).

Key Properties

• Molecular formula: Estimated to be C30H31Cl3NO8S\text{C}_{30}\text{H}_{31}\text{Cl}_3\text{NO}_8\text{S}C30H31Cl3NO8S based on analogous structures.
• 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 groups ensure 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. Benzylation of positions 4 and 6.
  3. Fmoc protection at position 3.
  4. 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 group.

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

Citations:

1. https://pubs.rsc.org/en/content/getauthorversionpdf/c9ob01610d
2. https://pubmed.ncbi.nlm.nih.gov/1394300/
3. https://pubs.acs.org/doi/10.1021/jo00296a055
4. https://patents.google.com/patent/US20040019198A1/en
5. https://pmc.ncbi.nlm.nih.gov/articles/PMC6474417/