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

Abstract

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.

Keywords:

• 20-hydroxylecdysone
• 20-hydroxylecdysone phosphate
• hypoglycemic activity

Acknowledgements

This work was financially supported by grants from the Natural Science Foundation of China (20825207, 20972083, and 21021001), the Program for Changjiang Scholars and Innovative Research Team in University (IRT0846), the National Basic Research Program of China (973 program, 2010CB833200), the National Science and Technology Major Project of China (2009ZX09310-002), and the State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry.

Notes

^†Correspondence should be addressed to X.-L. Wang for bioassay and Y. Qin for synthesis.