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

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

Ethyl 3,4-di-O-benzyl-2-deoxy-2-[(2,2,2-trichloroacetyl)amino]-6-O-(9-fluorenylmethoxycarbonyl)-1-thio-β-D-glucopyranoside is a synthetic thioglycoside derivative designed for 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.
• 3,4-di-O-benzyl groups: Permanent benzyl ether protections at positions 3 and 4, 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).
• 6-O-Fmoc group: A 9-fluorenylmethoxycarbonyl (Fmoc) carbonate at position 6, acting as a temporary protecting group cleavable under basic conditions (e.g., piperidine).

Key Properties

• Molecular formula: Likely C39H37Cl3NO7S\text{C}_{39}\text{H}_{37}\text{Cl}_3\text{NO}_7\text{S}C39H37Cl3NO7S (estimated from 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).
  • Benzyl 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 6-OH for subsequent glycosylation. The TCA group remains intact during these steps, enabling late-stage functionalization of the amino group.

Synthetic Considerations

• Preparation: Likely synthesized via sequential protection:
  1. Benzylation of glucose at positions 3 and 4.
  2. Fmoc protection at position 6.
  3. Trichloroacetylation of the 2-amino group.
  4. Thioglycoside formation at the anomeric position.
• 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://cymitquimica.com/products/3D-ME08389/129519-27-3/ethyl-3-o-benzyl-46-o-benzylidene-2-deoxy-2-n-phthalimido-b-d-thioglucopyranoside/
2. https://pubchem.ncbi.nlm.nih.gov/compound/2_3-Di-O-benzyl-4_6-O-ethylidene-D-glucopyranose
3. https://ppqs.gov.in/sites/default/files/schedule_to_insecticides_act_as_on_30.11.2020.pdf
4. https://pubchem.ncbi.nlm.nih.gov/compound/3_4_6-Tri-O-benzyl-2-deoxy-D-glucopyranose
5. https://www.sigmaaldrich.com/US/en/product/aldrich/r367478
6. https://www.chemicalbook.in/product/346-tri-o-benzyl-2-deoxy-d-glucopyranose-2118800
7. https://www.guidechem.com/hotproduct/e-p1288.html
8. https://refubium.fu-berlin.de/bitstream/handle/fub188/36869/Dissertation_Omoregbee-Leichnitz.pdf?sequence=3&isAllowed=y&save=y
9. https://getd.libs.uga.edu/pdfs/zhong_wei_200708_phd.pdf