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Epipolythiodiketopiperazine and trichothecene derivatives from the NaI-containing fermentation of marine-derived Trichoderma cf. brevicompactum

The Journal of Antibiotics volume 73, pages 559–567 (2020)Cite this article

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Abstract

The marine-derived fungus Trichoderma sp. TPU199 (cf. Trichoderma brevicompactum) produces pretrichodermamide A (1) and gliovirin (2), which possess a rare type of epipolythiodiketopiperazine (ETP) structure with a disulfide bridge between the α- and β-positions of two amino acid residues. We previously reported that this strain gave the halogenated ETPs, DC1149B (4), DC1149R (6), and iododithiobrevamide (7), when fermented with sodium halides (NaCl, NaBr, and NaI). Further analyses of the metabolites obtained under NaI-containing culture conditions resulted in the isolation of two new ETP derivatives (11 and 12) and three new trichothecene sesquiterpenes (13–15). The structures of 11 and 12, including their absolute configurations, were elucidated based on spectroscopic data for 11 and 12 and comparisons with those for 1 and related compounds, revealing that 11 was an epimer of 1 at the C-5 position and 12 was a trithio-derivative of 11. The structures of 13–15 were established by analyzing their 1D and 2D NMR data. The absolute configurations of 13–15 were assigned by comparing their experimental electronic circular dichroism (ECD) spectra with the calculated ECD spectrum of 13.

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Acknowledgements

This work was supported in part by JSPS KAKENHI Grant Numbers 25870660 and 16K21310 to HY, the Takeda Science Foundation to HY, and the Foundation for Japanese Chemical Research to HY. Calculations by Gaussian 09 were performed using supercomputing resources at the Cyberscience Center, Tohoku University. We are grateful to Mr T. Matsuki and S. Sato of Tohoku Medical and Pharmaceutical University for measuring mass spectra.

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Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Aoba-ku, Sendai, 981-8558, Japan

    Hiroyuki Yamazaki, Ohgi Takahashi, Ryota Kirikoshi, Akiho Yagi, Teruki Ogasawara, Yuki Bunya, Henki Rotinsulu, Ryuji Uchida & Michio Namikoshi

  2. Faculty of Mathematic and Natural Sciences, Sam Ratulangi University, Kampus Bahu, Manado, 95115, Indonesia

    Henki Rotinsulu

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  1. Hiroyuki Yamazaki
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Correspondence to Hiroyuki Yamazaki.

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Dedicated to Professor William Fenical in recognition of his contributions to the development of marine natural product chemistry.

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Yamazaki, H., Takahashi, O., Kirikoshi, R. et al. Epipolythiodiketopiperazine and trichothecene derivatives from the NaI-containing fermentation of marine-derived Trichoderma cf. brevicompactum. J Antibiot 73, 559–567 (2020). https://doi.org/10.1038/s41429-020-0314-5

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