Ethyl 6-O-(2-chloroacetyl)-4-O-(9-fluorenylmethoxycarbonyl)-3-O-levulinoyl-2-O-(2-naphthylmethyl)-1-thio-α-D-mannopyranoside

Ethyl 6-O-(2-chloroacetyl)-4-O-(9-fluorenylmethoxycarbonyl)-3-O-levulinoyl-2-O-(2-naphthylmethyl)-1-thio-α-D-mannopyranoside

Ethyl 6-O-(2-chloroacetyl)-4-O-(9-fluorenylmethoxycarbonyl)-3-O-levulinoyl-2-O-(2-naphthylmethyl)-1-thio-α-D-mannopyranoside is a sophisticated thioglycoside derivative that plays a crucial role in carbohydrate chemistry, particularly in the synthesis of oligosaccharides and glycoconjugates. This compound features an α-D-mannopyranoside core with strategically placed protective groups that facilitate selective reactivity during glycosylation processes.

Structural Features

• Core Structure: The backbone consists of an α-D-mannopyranoside unit with a thio group at the anomeric position (C1), enhancing its reactivity as a glycosyl donor.
• Protective Groups:
  • Chloroacetyl group at O-6, providing a labile protecting group that can be selectively removed under specific conditions, allowing for controlled reactions.
  • 9-Fluorenylmethoxycarbonyl (Fmoc) at O-4, which is base-labile and can be selectively removed to activate the hydroxyl for further reactions.
  • Levulinoyl group at O-3, offering acid-sensitive protection that can be removed to expose the hydroxyl for subsequent glycosylation.
  • Naphthylmethyl group at O-2, which provides steric hindrance and stability, facilitating selective reactions without interfering with other functional groups.

Synthesis Strategy

The synthesis typically involves several key steps:

1. Chloroacetylation: The hydroxyl group at O-6 is protected by chloracetylation using chloroacetic anhydride in the presence of a base.
2. Fmoc Protection: The hydroxyl group at O-4 is protected with Fmoc, which can be selectively removed later for further glycosylation reactions.
3. Levulinoylation: The O-3 position is modified with levulinic acid to introduce the levulinoyl group.
4. Naphthylmethyl Protection: The hydroxyl group at O-2 is protected using 2-naphthylmethyl chloride in the presence of a suitable base.

Physicochemical Properties

• Molecular Formula: Estimated as C₃₈H₄₄ClO₉S based on the substituent analysis.
• Appearance: Typically appears as a white crystalline solid, common for similar compounds in carbohydrate chemistry.
• Solubility: Soluble in polar aprotic solvents such as DMSO, DMF, and dichloromethane (DCM).
• Storage Conditions: Recommended to be stored at low temperatures (−20°C) under inert atmosphere to maintain stability.

Applications

• This compound serves as an important intermediate in synthesizing glycoconjugates and oligosaccharides due to its orthogonal protecting groups that allow for selective deprotection and further functionalization.
• It can also be utilized in studies related to glycan biology, facilitating the exploration of glycan interactions and functions in various biological systems.

Safety and Handling

• Generally considered non-hazardous but standard laboratory precautions should be observed when handling organic compounds.
• Use gloves and work in a well-ventilated area or fume hood to minimize exposure.

This compound exemplifies advanced strategies in carbohydrate synthesis, showcasing how protective group chemistry can be leveraged to achieve complex glycosidic structures efficiently.

Citations:

1. https://www.beilstein-journals.org/bjoc/articles/21/27
2. https://pmc.ncbi.nlm.nih.gov/articles/PMC6259426/
3. https://application.wiley-vch.de/books/sample/3527340106_c01.pdf
4. https://pubs.acs.org/doi/10.1021/ed074p1297
5. https://pmc.ncbi.nlm.nih.gov/articles/PMC8423405/
6. https://pubs.rsc.org/en/content/articlelanding/2017/ob/c6ob02278b
7. https://pubs.acs.org/doi/10.1021/ol401166x