Oku Naoya, Matoba Shouhei, Yamazaki Yohko Momose, Shimasaki Ryoko, Miyanaga Satoshi, Igarashi Yasuhiro
Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University , 5180 Kurokawa, Imizu, Toyama 939-0398, Japan.
J Nat Prod. 2014 Nov 26;77(11):2561-5. doi: 10.1021/np500276c. Epub 2014 Nov 6.
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.
由小单孢菌属产生的低氧选择性细胞毒素拉基西丁A的完整立体化学结构，通过广泛的化学降解和衍生化研究得以明确确定。在基于PGME衍生化的3-羟基-2,4,16-三甲基十七烷酸构型分析过程中，观察到了不规则的Δδ分布，这使得有必要对3-羟基进行进一步酰化以解决不一致性问题。对拉基西丁A的氢化衍生物、其开环产物以及两种具有不同烷基链长度的同系物进行了低氧选择性细胞毒性测试。结果表明，共轭二烯单元和合适的链长度对于拉基西丁A的独特活性都是必不可少的。
