Inoue Masayuki, Miyazaki Keisuke, Ishihara Yuuki, Tatami Atsushi, Ohnuma Yuyu, Kawada Yuuya, Komano Kazuo, Yamashita Shuji, Lee Nayoung, Hirama Masahiro
Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan.
J Am Chem Soc. 2006 Jul 26;128(29):9352-4. doi: 10.1021/ja063041p.
Ciguatoxins, the principal causative toxins of ciguatera seafood poisoning, are large ladder-like polycyclic ethers with the 13 ether rings ranging from five- to nine-membered. In this paper, we describe the total synthesis of the two most toxic members of the ciguatoxin family, ciguatoxin 1 and 51-hydroxyCTX3C 2, based on a unified synthetic strategy. The key features in our syntheses were (i) direct construction of the O,S-acetal from the corresponding left and right wing fragments (3, 4, 14); (ii) stereo- and chemoselective radical reaction of the alpha-oxyradical with pentafluorophenyl acrylate to achieve cyclization of the seven-membered G-ring; (iii) ring-closing metathesis reaction to build the nine-membered F-ring; and (iv) an efficient protective group strategy using the oxidatively removable 2-naphthylmethyl groups.
雪卡毒素是雪卡鱼中毒的主要致病毒素，是一种大型阶梯状多环醚，具有13个醚环，环的大小从五元到九元不等。在本文中，我们基于统一的合成策略描述了雪卡毒素家族中两种毒性最强的成员——雪卡毒素1和51-羟基CTX3C 2的全合成。我们合成过程中的关键特征包括：(i) 从相应的左右翼片段（3、4、14）直接构建O,S-缩醛；(ii) α-氧自由基与五氟苯基丙烯酸酯发生立体和化学选择性自由基反应，实现七元G环的环化；(iii) 闭环复分解反应构建九元F环；(iv) 使用可氧化去除的2-萘甲基基团的高效保护基策略。
