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Synthetic studies for destruxins and biological evaluation for osteoclast-like multinucleated cells: a review

The Journal of Antibiotics volume 75, pages 420–431 (2022)Cite this article

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Abstract

Synthesis of various destruxin analogs was accomplished using Shiina’s macrolactonization as a key reaction. Combinatorial synthesis of cyclization precursors using solid-phase peptide synthesis and macrolactonization in solution were successful. In the synthesis of destruxin E and its analogs, the hydroxyacid–proline (HA1–Pro2) dipeptide with an acetonide-protected diol moiety was synthesized in an asymmetric manner, and the protected diol was converted to an epoxide after macrocyclization. Destruxin E was synthesized on a gram scale using solution-phase synthesis. The structure-activity relationships of destruxins were elucidated through biological evaluation of synthetic destruxins A, B, and E and their analogs for morphological changes in osteoclast-like multinucleated cells.

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Funding

This work was supported in part by JSPS KAKENHI (Grant No. JP26282208, JP23710264 and JP15H05837), the Platform Project for Supporting Drug Discovery and Life Science Research from AMED (Grand No. JP21am0101095 and JP21am0101100), the Naito Foundation, and Takeda Science Foundation.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Pure and Applied Sciences, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8571, Japan

    Masahito Yoshida

  2. Department of Applied Biological Chemistry, Chubu University, 1200 Matsumoto-cho, Kasugai, Aichi, 487-8501, Japan

    Hiroshi Nakagawa

  3. Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aza-aoba, Aramaki, Aoba-ku, Sendai, 980-8578, Japan

    Takayuki Doi

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  1. Masahito Yoshida
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Correspondence to Takayuki Doi.

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Yoshida, M., Nakagawa, H. & Doi, T. Synthetic studies for destruxins and biological evaluation for osteoclast-like multinucleated cells: a review. J Antibiot 75, 420–431 (2022). https://doi.org/10.1038/s41429-022-00540-8

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