Absolute configuration of naturally occurring glabridin.

Charlotte Simmler,Guido F Pauli,Frank R Fronczek,Bernard D Santarsiero

doi:10.1107/s0108270113018842

Abstract

The title compound {systematic name: 4-[(3R)-8,8-dimethyl-3,4-dihydro-2H-pyrano[2,3-f]chromen-3-yl]benzene-1,3-diol, commonly named glabridin}, C20H20O4, is a species-specific biomarker from the roots Glycyrrhiza glabra L. (European licorice, Fabaceae). In the present study, this prenylated isoflavan has been purified from an enriched CHCl3 fraction of the extract of the root, using three steps of medium-pressure liquid chromatography (MPLC) by employing HW-40F, Sephadex LH-20 and LiChroCN as adsorbents. Pure glabridin was crystallized from an MeOH-H2O mixture (95:5 v/v) to yield colorless crystals containing one molecule per asymmetric unit (Z' = 1) in the space group P212121. Although the crystal structure has been reported before, the determination of the absolute configuration remained uncertain. Stereochemical analysis, including circular dichroism, NMR data and an X-ray diffraction data set with Bijvoet differences, confirms that glabridin, purified from its natural source, is found only in a C3 R configuration. These results can therefore be used as a reference for the assignment of the configuration and enantiopurity of any isolated or synthetic glabridin sample.

Highlights

Glabridin, (I), is a prenylated isoflavan, which has previously been isolated from the roots of Glycyrrhiza glabra (Shibata & Saitoh, 1978; Zhang & Ye, 2009)
After the final step of the medium-pressure liquid chromatography (MPLC) purification process, natural glabridin was crystallized from a mixture of methanol and water to give clear colorless crystals of (I) containing one molecule per asymmetric unit (Z0 = 1) in the space group P212121 (Fig. 1)
The one-dimensional 1H NMR spectra (600 MHz, in DMSO-d6 and CDCl3; see Supplementary materials) obtained for the present sample of glabridin are in accordance with previously published data (Kinoshita et al, 1996; Kim et al, 2009)

Summary

Introduction

Glabridin, (I), is a prenylated isoflavan, which has previously been isolated from the roots of Glycyrrhiza glabra (Shibata & Saitoh, 1978; Zhang & Ye, 2009).

Synthesis and crystallization

Refinement

Results and discussion

Conclusions

H-6 H-3A H-5A H-6A 2A-OH 4A-OH H-3B H-4B H3-5B H3-6B