Synthetic Access to l-Guluronic Acid via Fluorine-Directed C-5 Epimerization

Area of Science:

• Carbohydrate Chemistry
• Synthetic Organic Chemistry
• Biochemistry

Background:

• l-Guluronic acid (l-GulA) is crucial for alginate structure and *Pseudomonas aeruginosa* pathogenesis.
• The high cost of l-GulA limits its applications in various fields.
• Efficient synthesis of l-GulA is needed to overcome these limitations.

Purpose of the Study:

• To develop a short and efficient synthetic route for producing l-guluronic acid (l-GulA).
• To enable wider exploitation of l-GulA in existing and novel applications by reducing its cost.

Main Methods:

• Synthesis of an l-GulA building block from a d-mannose thioglycoside.
• Utilizing a fluorine-directing effect for stereoselective C-5 epimerization.
• Employing DFT calculations to understand substituent effects conferring selectivity.

Main Results:

• A novel, efficient synthetic pathway to an l-GulA precursor was established.
• Stereoselective C-5 epimerization was achieved, guided by fluorine substituents.
• DFT calculations provided insights into the mechanism of stereoselectivity.

Conclusions:

• The developed synthetic route offers a cost-effective method for l-GulA production.
• This advancement facilitates broader use of l-GulA in alginate research and biotechnology.
• Understanding the stereochemical control mechanism aids future synthetic strategies.