Ethyl 2-deoxy-2-[(2,2,2-trichloroacetyl)amino]-1-thio-β-D-glucopyranoside

Ethyl 2-deoxy-2-[(2,2,2-trichloroacetyl)amino]-1-thio-β-D-glucopyranoside

Ethyl 2-deoxy-2-[(2,2,2-trichloroacetyl)amino]-1-thio-β-D-glucopyranoside is a synthetic thioglycoside derivative designed for advanced carbohydrate chemistry applications. This compound integrates a trichloroacetyl (TCA) protecting group on the amino function, which is commonly used in carbohydrate synthesis to protect amino groups during glycosylation reactions.

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.
• 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). The TCA group is used as an N-protective group in carbohydrate synthesis, similar to its application in nucleoside synthesis.

Key Properties

• Molecular formula: Estimated to be C10H14Cl3NO4S\text{C}_{10}\text{H}_{14}\text{Cl}_3\text{NO}_4\text{S}C10H14Cl3NO4S 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.
  • 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 TCA group remains intact during glycosylation 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. 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 TCA group.

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

Citations:

1. https://comptes-rendus.academie-sciences.fr/chimie/articles/10.1016/j.crci.2010.05.010/
2. https://pubs.rsc.org/en/content/getauthorversionpdf/c9ob00573k
3. https://application.wiley-vch.de/books/sample/3527340106_c01.pdf
4. https://pmc.ncbi.nlm.nih.gov/articles/PMC6259426/
5. https://pubmed.ncbi.nlm.nih.gov/16634100/
6. https://pubs.acs.org/doi/10.1021/jo01281a025
7. https://pubs.acs.org/doi/full/10.1021/jo01273a052
8. https://snyder-group.uchicago.edu/downloads/Lectures2020/Protecting%20Groups.pdf