Synthetic Methods and Application of Phosphoester Prodrugs

Compared with the original drugs, the phosphoester prodrugs can not only improve the targeting, stability and bioavailability of the drugs, reduce toxicity and side effects, but also mask the unpleasant odor of the drugs, improve water solubility, and provide better access to the drugs. Phosphorylation of hydroxyl-containing drugs is one of the most important methods for their prodrug design. According to different valences of central phosphorus atoms and chemical structures, the phosphorylation reagents include tetracoordinated P(V) compounds, tricoordinated P (III) compounds and H-phosphite esters. The advances of these reagents in the synthesis of phosphoester prodrugs were reviewed, and the applications of these prodrugs were elaborated. Finally, the advantages and limitations of various phosphorylation reagents were summarized, and the development trend was prospected based on the application cases of continuous flow reaction technology.

Automated summary

Compared to the original drugs, phosphoester prodrugs have several advantages including improved targeting, stability, and bioavailability of the drugs, reduced toxicity and side effects, masked unpleasant odor, enhanced water solubility, and better access to the drugs. The phosphorylation of hydroxyl-containing drugs is an essential method for prodrug design. Different phosphorylation reagents, such as tetracoordinated P(V) compounds, tricoordinated P(III) compounds, and H-phosphite esters, have been reviewed for their synthesis and application in phosphoester prodrugs. The article concludes with a summary of the advantages and limitations of these phosphorylation reagents and prospects for future development based on continuous flow reaction technology.