Complete Stereochemistry and Preliminary Structure–Activity Relationship of Rakicidin A, a Hypoxia-Selective Cytotoxin from <i>Micromonospora</i> sp.
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- Naoya Oku
- Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan
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- Shouhei Matoba
- Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan
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- Yohko Momose Yamazaki
- Institute of Microbial Chemistry, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan
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- Ryoko Shimasaki
- Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan
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- Satoshi Miyanaga
- Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan
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- Yasuhiro Igarashi
- Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan
説明
The complete stereochemistry of rakicidin A, a hypoxia-selective cytotoxin produced by Micromonospora sp., was unambiguously established by extensive chemical degradation and derivatization studies. During the PGME derivatization-based configurational analysis of 3-hydroxy-2,4,16-trimethylheptadecanoic acid, an irregular Δδ distribution was observed, which necessitated further acylation of the 3-hydroxy group to resolve the inconsistency. A hydrogenated derivative of rakicidin A, its ring-opened product, and two congeners with different alkyl chain lengths were tested for hypoxia-selective cytotoxicity. The results indicated that both the conjugated diene unit and appropriate chain length are essential for the unique activity of rakicidin A.
収録刊行物
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- Journal of Natural Products
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Journal of Natural Products 77 (11), 2561-2565, 2014-11-06
American Chemical Society (ACS)