3-Fluoro-GalNAc Derivative for Glycobiology and Delivery Research (CAS 1616958-99-6)
This protected 3-fluoro analogue of N-acetylgalactosamine provides a building block for glycobiology, nucleic acid delivery research, and fluorine-19 NMR studies.
GalNAc (N-acetylgalactosamine) and its derivatives are widely used in research on tissue-targeted delivery. This GalNAc analogue combines site-specific fluorination with acetyl protection, offering a tool for studying carbohydrate biology and developing nucleic acid delivery systems.
Chemical information
• Chemical name: 2-acetamido-2,3-dideoxy-3-fluoro-α-D-galactopyranose 1,4,6-triacetate
• CAS number: 1616958-99-6
• Molecular formula: C₁₄H₂₀FNO₈
• Molecular weight: 349.31 g/mol
• Classification: Fluorinated compound
Structural features
Fluorine at C-3. Fluorine replaces the hydroxyl group at C-3. Its high electronegativity and small van der Waals radius (1.47 Å) allow it to modify the electronic environment without greatly increasing steric bulk. This substitution can influence lipophilicity and metabolic stability.
Acetyl protection. The hydroxyl groups at C-1, C-4, and C-6 are acetylated. This protects them during multistep organic synthesis and can simplify handling and storage. Acetylation may also aid cell entry. Intracellular esterases can remove the acetyl groups, releasing the corresponding 3-fluoro-GalNAc analogue.
Defined stereochemistry. The α configuration provides a defined stereochemical starting point for synthesizing particular glycosidic linkages and studying enzyme reactions or ligand recognition.
Research applications
1. Liver-targeted delivery and ASGPR
GalNAc binds the asialoglycoprotein receptor (ASGPR), which is abundant on hepatocytes. This fluorinated derivative can be investigated as a building block for GalNAc clusters. C-3 fluorination provides a way to test changes in susceptibility to glycosidases and to assess whether altered ligand electronics affect binding to ASGPR or circulation time.
2. Fluorine-19 NMR probes
Biological samples typically have a low fluorine-19 background. A fluorinated sugar can therefore serve as a reporter in NMR experiments designed to track metabolism, conformational changes, and protein interactions. This can support studies of how carbohydrate-based candidates behave in biological systems.
3. Bioisosteric design in carbohydrate chemistry
Fluorine is used as a hydroxyl bioisostere in medicinal chemistry. Replacing the C-3 hydroxyl can block reactions at that position and provides a way to study how the change affects metabolic pathways and bioavailability. Incorporating fluorinated analogues into synthetic glycoconjugates also allows researchers to explore how glycosylation influences protein folding, physicochemical properties, and signaling.
Conclusion
This protected 3-fluoro-GalNAc derivative brings together carbohydrate synthesis and fluorine chemistry. It provides a building block for exploring siRNA and antisense oligonucleotide delivery, fluorine-based imaging and spectroscopy, and the synthesis of complex glycans.
Prepared by KASONS. For research use only.