Complete Stereochemistry and Preliminary Structure-Activity Relationship of Rakicidin A, a Hypoxia-Selective Cytotoxin from Micromonospora sp.
Complete Stereochemistry and Preliminary Structure-Activity Relationship of Rakicidin A, a Hypoxia-Selective Cytotoxin from Micromonospora sp.
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DOI：
10.1021/np500276c
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发表时间：
2014-11-01
影响因子：
5.1
通讯作者：
Igarashi, Yasuhiro
中科院分区：
文献类型：
--
作者：
Oku, Naoya;Matoba, Shouhei;Igarashi, Yasuhiro
Rakicidin A是小单孢菌产生的一种低氧选择性细胞毒素，通过广泛的化学降解和衍生化研究明确地建立了它的完整立体化学。在基于PGME衍生化的3-羟基-2，4，16-三甲基十七烷酸的构型分析中，观察到了不规则的？d分布，这需要3-羟基的进一步酰化来解决这一矛盾。对Rakicidin A的氢化衍生物、其开环产物和两种不同烷基链长的同系物进行了低氧选择性细胞毒性试验。结果表明，共轭双烯单元和合适的链长都是雷基菌素A具有独特活性所必需的。
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 ?d 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.