Synthesis of prenylated flavonols and their potents as estrogen receptor modulator

Zhenru Tao,Liang Gong,Yueming Jiang,Juan Liu,Bao Yang

doi:10.1038/s41598-017-12640-9

Abstract

Prenylated flavonols are known as phytoestrogen and have good bioactivties. However, their abundances in nature are pretty low. It is required to find an efficient synthesis technique. Icariin is a prenylated flavonol glycoside with low cost. It can be used to synthesize different prenylated flavonols. A combination of cellulase and trifluoacetic acid hydrolysis could effectively remove rhamnose and glucose from icariin. Icaritin, anhydroicaritin and wushanicaritin were the leading prenylated flavonol products. Their affinities to estrogen receptors α and β were predicted by docking study. The weak affinity of wushanicaritin indicated that prenyl hydroxylation impaired its affinity to estrogen receptor β. The prenyl cyclization led to a loss of affinity to both receptors. The interactions between icaritin and ligand binding cavity of estrogen receptor β were simulated. π-π stacking and hydrophobic forces were predicted to be the dominant interactions positioning icaritin, which induced the helix (H12) forming an activated conformation.

Highlights

Prenylated flavonoids are an important sub-class of flavonoids, which combine a flavonoid skeleton with a lipophilic prenyl side chain[1]
Though Epimedium genus is a good source of icaritin derivatives, the icaritin level is very low when determined by HPLC-MS16
There was only one product generated after enzyme hydrolysis (Fig. 1)

Summary

Introduction

Prenylated flavonoids are an important sub-class of flavonoids, which combine a flavonoid skeleton with a lipophilic prenyl side chain[1]. Hydrolysis by cellulase first and TFA: Icariin (100 mg) were added into 25 ml of water. Hydrolysis by TFA first and cellulose: Icariin (100 mg) were added into 25 ml of water. The reaction product of icariin hydrolysed by cellulase at 37 °C for 2.5 h.

Results

Conclusion