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Total syntheses of schizandriside, saracoside and (±)-isolariciresinol with antioxidant activities

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Abstract

Lignans are widely distributed in plants and exhibit significant pharmacological effects, including anti-tumor and antioxidative activities. Here, we describe the total synthesis of schizandriside (1), a compound we previously isolated from Saraca asoca by monitoring antioxidative activity using the 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay. Starting from a tandem Michael-aldol reaction, the lignan skeleton was synthesized in 6 steps, including a cyclization step. To determine the stereochemistry of 1, we synthesized the natural product (±)-isolariciresinol (18) from alcohol 17. Comparison of the spectral data showed good agreement. Glycosylation was investigated using four different glycosyl donors. Only the Koenigs–Knorr condition using silver trifluoromethanesulfonate with 1,1,3,3-tetramethylurea provided the glycosylated product. Deprotection and purification using reverse-phase high-performance liquid chromatography gave schizandriside (1) and its diastereomer saracoside (2). Synthesized 1, 2 and 18 showed antioxidant activity with IC50 = 34.4, 28.8, 53.0 μM, respectively.

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Acknowledgements

This study was supported by KAKENHI Grant numbers 17H03992 and 15H04650, Suzuken Memorial Foundation, Takeda Science Foundation, Astellas Foundation for Research on Metabolic Disorders, the Naito Foundation, Strategic Priority Research Promotion Program, Chiba University, ‘Phytochemical Plant Molecular Sciences’, JSPS A3 Foresight Program, and a Workshop on Chirality at Chiba University (WCCU). This work was inspired by the international and interdisciplinary environment of the JSPS Core-to-Core Program ‘Asian Chemical Biology Initiative’.

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Authors and Affiliations

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

    Mana Sampei, Midori A. Arai & Masami Ishibashi

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  1. Mana Sampei
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  2. Midori A. Arai
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  3. Masami Ishibashi
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Correspondence to Midori A. Arai or Masami Ishibashi.

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Sampei, M., Arai, M.A. & Ishibashi, M. Total syntheses of schizandriside, saracoside and (±)-isolariciresinol with antioxidant activities. J Nat Med 72, 651–654 (2018). https://doi.org/10.1007/s11418-018-1198-6

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  • DOI: https://doi.org/10.1007/s11418-018-1198-6

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