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Is 18α-Glycyrrhizin a real natural product? Improved preparation of 18α-Glycyrrhizin from 18β-Glycyrrhizin as a positive standard for HPLC analysis of licorice extracts

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Abstract

18α-Glycyrrhizin is an epimer of 18β-glycyrrhizin, a major component of licorice (Glycyrrhiza sp.), which is widely used as a traditional medicine. Whether 18α-glycyrrhizin is a real natural product has been debated in the long history of glycyrrhizin chemistry because 18β-glycyrrhizin is epimerizable to a more thermodynamically stable 18α-glycyrrhizin under aqueous alkali conditions. We improved the preparation of 18α-glycyrrhizin from 18β-glycyrrhizin by successive epimerization reactions of 18β-glycyrrhizin, trimethyl esterification of the resulting epimerized mixture, and alkaline hydrolysis of a purified 18α-glycyrrhizin trimethyl ester. Approaches to the possible presence of 18α-glycyrrhizin in licorice extracts by HPLC using synthetic 18α-glycyrrhizin as a positive standard strongly suggested that 18α-glycyrrhizin could naturally exist as a minor congener of glycyrrhizin derivatives in Glycyrrhiza species.

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Acknowledgements

We thank Ms Sayaka Kado, Center for Analytical Instrumentation, Chiba University, for recording HRESI-MS spectra.

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Authors and Affiliations

  1. Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo, Chiba, 260-8675, Japan

    Kritamorn Jitrangsri & Masami Ishibashi

  2. Tokiwa Phytochemical Co., Ltd., 158 Kinoko, Sakura, Chiba, 285-0801, Japan

    Kazuaki Kamata, Mana Akiba, Yoshie Yajiri, Jin Tatsuzaki & Tsutomu Ishikawa

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  1. Kritamorn Jitrangsri
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  2. Kazuaki Kamata
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Correspondence to Tsutomu Ishikawa.

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Jitrangsri, K., Kamata, K., Akiba, M. et al. Is 18α-Glycyrrhizin a real natural product? Improved preparation of 18α-Glycyrrhizin from 18β-Glycyrrhizin as a positive standard for HPLC analysis of licorice extracts. J Nat Med 76, 367–378 (2022). https://doi.org/10.1007/s11418-021-01589-9

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