Synthesis of 5- and 8-Deoxytetrodotoxin.
Synthesis of 5- and 8-Deoxytetrodotoxin.
复制标题
5-和8-脱氧河豚毒素的合成。
DOI：
10.1002/asia.201402202
复制
发表时间：
2014
期刊：
影响因子：
--
通讯作者：
T.
中科院分区：
文献类型：
--
作者：
Satake;Y.; Adachi;M.; Tokoro;S.; Yotsu-Yamashita;M.; Isobe;M.; Nishikawa;T.
河豚毒素（Tetrodotoxin）是河豚鱼中毒的主要毒性物质之一，由于其结构复杂，生物活性强，是最著名的海洋天然产物之一，可导致致命性中毒。对河豚毒素及其类似物的连续合成研究以阐明与河豚毒素相关的生物学有趣的问题，导致了多种河豚毒素衍生物的通用路线的发展。为了研究河豚毒素与电压门控钠通道的结构-活性关系，本研究描述了从一种新设计的多功能中间体以有效的方式首次全合成5-脱氧河豚毒素（河豚毒素的天然类似物）和8-脱氧河豚毒素（非天然类似物）。对这些化合物的生物活性的估计揭示了C-5和C-8位置上的羟基对电压门控钠通道抑制的重要性。
Tetrodotoxin, a toxic principle of puffer fish intoxication, is one of the most famous marine natural products owing to its complex structure and potent biological activity, which leads to fatal poisoning. Continuous synthetic studies on tetrodotoxin and its analogues to elucidate biologically interesting issues associated with tetrodotoxin have led to the development of versatile routes for a variety of tetrodotoxin derivatives. With the aim of investigating the structure–activity relationship of tetrodotoxin with voltage‐gated sodium channels, this study describes the first total syntheses of 5‐deoxytetrodotoxin, a natural analogue of tetrodotoxin, and 8‐deoxytetrodotoxin, an unnatural analogue, from a newly designed, versatile intermediate in an efficient manner. An estimation of the biological activities of these compounds reveals the importance of the hydroxy groups at the C‐5 and C‐8 positions on the inhibition of voltage‐gated sodium channels.