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

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

Ethyl 6-O-benzyl-2-deoxy-2-[(2,2,2-trichloroacetyl)amino]-4-O-(9-fluorenylmethoxycarbonyl)-3-O-levulinoyl-1-thio-β-D-glucopyranoside 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-glucopyranoside 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.
• 6-O-benzyl group: A permanent benzyl ether protection at position 6, providing stability under acidic/basic conditions and enabling selective deprotection later.
• 2-Deoxy-2-trichloroacetamido 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).
• 4-O-Fmoc group: A 9-fluorenylmethoxycarbonyl (Fmoc) carbonate at position 4, acting as a temporary protecting group cleavable under basic conditions (e.g., piperidine).
• 3-O-levulinoyl group: A levulinoyl ester at position 3, acting as a temporary protecting group that can be cleaved under mild conditions.

Key Properties

• Molecular formula: Estimated to be C34H34Cl3NO8S\text{C}_{34}\text{H}_{34}\text{Cl}_3\text{NO}_8\text{S}C34H34Cl3NO8S 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 and levulinoyl groups ensure regioselective reactivity, while Fmoc allows orthogonal deprotection for sequential glycosylation.
  • Trichloroacetyl 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 4-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. Benzylation of glucose at position 6.
  2. Levulinoylation at position 3.
  3. Fmoc protection at position 4.
  4. Trichloroacetylation of the 2-amino group.
  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 piperidine (Fmoc cleavage) and Zn/AcOH (TCA removal).

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/