Intramolecular radical cyclization-ring-closing metathesis approach to fused polycyclic ethers. Convergent synthesis and conformational analysis of the (E)FGH ring system of ciguatoxin.
Intramolecular radical cyclization-ring-closing metathesis approach to fused polycyclic ethers. Convergent synthesis and conformational analysis of the (E)FGH ring system of ciguatoxin.
复制标题
稠合多环醚的分子内自由基环化-闭环复分解方法。
DOI：
10.1021/jo010974p
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
K. Tachibana
中科院分区：
文献类型：
--
作者：
M. Sasaki;Tetsuji Noguchi;K. Tachibana
已开发出一种合成西加毒素（引起西加鱼中毒的毒素）的(E)FGH环系4的汇聚合成路线。该合成的特点包括：汇聚偶联形成二氧六环缩醛，通过苯硫醇二乙基铝或苯硒醇二异丁基铝进行区域选择性缩醛裂解，随后进行分子内自由基环化构建氧杂环庚烷环G，以及通过关环复分解反应形成六氢噁嗪环F。四环模型体系4的六氢噁嗪环F以两种构象异构体（UP和DOWN构象异构体）5:1的平衡混合物形式存在，其中UP构象异构体占优势。这是首次重现了对UP构象异构体相对于DOWN构象异构体的偏好的示例，这种偏好在天然西加毒素中已被观察到。
A convergent synthetic route to the (E)FGH ring system 4 of ciguatoxins, the causative toxins for ciguatera fish poisoning, has been developed. The synthesis features convergent coupling to form dioxane acetal, regioselective acetal cleavage by diethylaluminum phenylthiolate or diisobutylaluminum phenylselenolate followed by intramolecular radical cyclization to construct the oxepane ring G, and a ring-closing metathesis reaction to form the hexahydrooxonine ring F. The hexahydrooxonine ring F of tetracyclic model system 4 existed as a 5:1 equilibrium mixture of two conformers (UP and DOWN conformers), with the UP one predominating. This is the first illustration that reproduces the preference for the UP conformer over the DOWN one, which preference was observed for natural ciguatoxins.