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Proposal for structure revision of pinofuranoxin A through total syntheses of stereoisomers

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Abstract

The relative configuration of the epoxide functionality in pinofuranoxin A (1), α-alkylidene-β-hydroxy-γ-methyl-γ-butyrolactone with trans-epoxy side chain isolated by Evidente et al. in 2021, was revised by DFT-based spectral reinvestigations and stereo-controlled synthesis. The present investigation demonstrates the difficulty of the configurational elucidation of the stereogenic centers on the conformationally flexible acyclic side-chains. Sharpless’s enantioselective epoxidations and dihydroxylations were quite effective in the reinvestigations of the configurations. As our syntheses made all diastereomers available, these would be quite effective in the next structure-biological activity relationship studies.

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Authors and Affiliations

  1. Laboratory of Natural Products Chemistry, School of Pharmaceutical Sciences, Wakayama Medical University, 25-1 Shichibancho, Wakayama, 640-8156, Japan

    Kazuki Ujiie, Chiaki Tanaka & Satoru Tamura

  2. Laboratory of Natural Products for Drug Discovery, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-Oka, Suita, Osaka, 565-0871, Japan

    Masayoshi Arai

  3. Department of Biochemistry and Molecular Biology, Faculty of Agriculture and Life Science, Hirosaki University, 3-Bunkyo-Cho, Hirosaki, 036-8561, Japan

    Masaru Hashimoto

  4. Department of Medicinal and Organic Chemistry, School of Pharmacy, Iwate Medical University, 1-1-1 Idai-Dori, Yahaba-Cho, Shiwa-Gun, Iwate, 028-3694, Japan

    Yuki Yoshida & Tomikazu Kawano

Authors
  1. Kazuki Ujiie
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  2. Chiaki Tanaka
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  3. Masayoshi Arai
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  4. Masaru Hashimoto
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  5. Yuki Yoshida
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  7. Satoru Tamura
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Contributions

Conceived and designed the experiments: Satoru Tamura, Tomikazu Kawano, and Masayoshi Arai. Performed the experiments: Kazuki Ujiie, Chiaki Tanaka, and Yuki Yoshida. Analyzed DFT calculation with DP4 method and ECD calculation: Masaru Hashimoto.

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Correspondence to Satoru Tamura.

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Ujiie, K., Tanaka, C., Arai, M. et al. Proposal for structure revision of pinofuranoxin A through total syntheses of stereoisomers. J Nat Med (2024). https://doi.org/10.1007/s11418-024-01810-5

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  • DOI: https://doi.org/10.1007/s11418-024-01810-5

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