An effective reagent to functionalize alcohols with phosphocholine

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Biochemistry

Background:

• Phosphocholine is a vital molecule found in biological systems, acting as a precursor and degradation product of choline.
• It is a key component of various biomolecules, including lipids and oligosaccharides.

Purpose of the Study:

• To develop an air and bench stable phosphocholine donor for efficient synthesis of phosphocholine derivatives.
• To establish a cost-effective method for producing miltefosine, a crucial drug for leishmaniasis treatment.

Main Methods:

• A one-pot, three-step synthesis involving phosphitylation, oxidation, and phosphate deprotection was employed.
• The developed method was evaluated using various alcohol acceptors.

Main Results:

• High yields of phosphocholine derivatives were achieved using the novel synthetic route.
• The synthesis of miltefosine was demonstrated, with a projected production cost of $25 per gram, a significant reduction from the current $1500 per gram.

Conclusions:

• The developed phosphocholine donor and synthetic strategy offer a highly efficient and accessible method for producing valuable phosphocholine derivatives.
• This breakthrough has the potential to make essential treatments like miltefosine more affordable and accessible globally.