Total Synthesis and Biological Evaluation of Irciniastatin A (a.k.a. Psymberin) and Irciniastatin B

Shun Ichiro Uesugi, Tsubasa Watanabe, Takamichi Imaizumi, Yu Ota, Keisuke Yoshida, Haruna Ebisu, Takumi Chinen, Yoko Nagumo, Masatoshi Shibuya, Naoki Kanoh, Takeo Usui, Yoshiharu Iwabuchi

研究成果: Article

17 引用 (Scopus)

抜粋

Irciniastatin A (a.k.a. psymberin) and irciniastatin B are members of the pederin natural product family, which have potent antitumor activity and structural complexity. Herein, we describe a full account of our total synthesis of (+)-irciniastatin A and (-)-irciniastatin B. Our synthesis features the highly regioselective Eu(OTf)3-catalyzed, DTBMP-assisted epoxide ring opening reaction with MeOH, which enabled a concise synthesis of the C1-C6 fragment, extensive use of AZADO (2-azaadamantane N-oxyl) and its related nitroxyl radical/oxoammonium salt-catalyzed alcohol oxidation throughout the synthesis, and a late-stage assembly of C1-C6, C8-C16, and C17-C25 fragments. In addition, for the synthesis of (-)-irciniastatin B, we achieved the C11-selective control of the oxidation stage via regioselective deprotection and AZADO-catalyzed alcohol oxidation. The synthetic irciniastatins showed high levels of cytotoxic activity against mammalian cells. Furthermore, chemical footprinting experiments using synthetic compounds revealed that the binding site of irciniastatins is the E-site of the ribosome.

元の言語English
ページ(範囲)12333-12350
ページ数18
ジャーナルJournal of Organic Chemistry
80
発行部数24
DOI
出版物ステータスPublished - 2015 11 6

ASJC Scopus subject areas

  • Organic Chemistry

フィンガープリント Total Synthesis and Biological Evaluation of Irciniastatin A (a.k.a. Psymberin) and Irciniastatin B' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

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    Uesugi, S. I., Watanabe, T., Imaizumi, T., Ota, Y., Yoshida, K., Ebisu, H., Chinen, T., Nagumo, Y., Shibuya, M., Kanoh, N., Usui, T., & Iwabuchi, Y. (2015). Total Synthesis and Biological Evaluation of Irciniastatin A (a.k.a. Psymberin) and Irciniastatin B. Journal of Organic Chemistry, 80(24), 12333-12350. https://doi.org/10.1021/acs.joc.5b02256