Synthesis of a novel phosphate analog of 20-hydroxylecdysone with potent hypoglycemic activity.

A novel, water-soluble 20-hydroxylecdysono-20,22-phosphoric acid 2 and its sodium salt 3 were designed and synthesized from 20-hydroxylecdysone 1 in six steps and with 67% overall yield. The synthesized phosphoric acid 2 exhibited hypoglycemic activity >40-fold more potent than that of 20-hydroxylecdysone 1 at concentrations between 2 × 10⁻⁷ and 2 × 10⁻⁸ mol/l in a glucose consumption test in HepG2 cells. At a concentration of 2 × 10⁻⁹ mol/l, phosphoric acid 2 was still active, causing a maximum increase in glucose consumption of more than 500%, while 20-hydroxylecdysone 1 was inactive.