Design, synthesis, and sustained-release property of 1,3-cyclic propanyl phosphate ester of 18β-glycyrrhetinic acid.

A new class of potential prodrugs, 1,3-cyclic propanyl phosphate esters of 18β-glycyrrhetic acid, was designed and synthesized through the key reaction of 18β-glycyrrhetic acid with 1,3-cyclic propanyl phosphate ester catalysed by lithium diisopropylamide. The sustained-release properties of 1,3-cyclic propanyl phosphate esters of 18β-glycyrrhetic acid in vivo were also investigated. The animal experiments showed that 18β-glycyrrhetic acid was released from 1,3-cyclic propanyl phosphate esters of 18β-glycyrrhetic acid at a steady rate in rats and the plasma concentrations of 18β-glycyrrhetic acid were nearly stable. The result indicated that 1,3-cyclic propanyl phosphate esters of 18β-glycyrrhetic acid have sustained-release properties to avoid the quick metabolism of 18β-glycyrrhetic acid. These prodrugs are highlighted as a promising new strategy to improve 18β-glycyrrhetic acid metabolism.