(+)-Saxitoxin: A first and second generation stereoselective synthesis
(+)-Saxitoxin: A first and second generation stereoselective synthesis
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DOI：
10.1021/ja071501o
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发表时间：
2007-08-15
影响因子：
15
通讯作者：
Du Bois, J.
中科院分区：
文献类型：
--
作者：
Fleming, James J.;McReynolds, Matthew D.;Du Bois, J.
描述了双胍毒素 (+)-石房蛤毒素 (STX) 的立体选择性合成，该毒素与赤潮和麻痹性贝类中毒有关。我们对这种独特的天然产物的研究方法是通过一种不寻常的九元环胍中间体 39 转化为定义 STX 的三环骨架。该策略的有效性值得注意，因为只需四个步骤即可将 39 转化为目标分子，其中包括 OsCl3 催化的四电子烯烃氧化。关键的单环胍的构建是通过两个通道实现的，第一个通道利用 Rh 催化的 C-H 胺化，并突出了一类新型杂环 N,O-缩醛作为亚胺离子等价物，用于制备官能化胺。获得 39 的第二条途径依赖于基于丝氨酸的硝酮的立体选择性乙酰化物二价阴离子加成，从而促进从商业材料仅通过 14 个线性步骤即可制备 STX。
A stereoselective synthesis of the bis-guanidinium toxin (+)-saxitoxin (STX), the agent infamously associated with red tides and paralytic shellfish poisoning, is described. Our approach to this unique natural product advances through an unusual nine-membered ring guanidine intermediate 39 en route to the tricyclic skeleton that defines STX. The effectiveness of this strategy is notable, as only four steps are needed to transform 39 into the target molecule, including a four-electron alkene oxidation catalyzed by OsCl3. Construction of the critical monocyclic guanidine has been achieved through two channels, the first of which makes use of Rh-catalyzed C-H amination and highlights a novel class of heterocyclic N,O-acetals as iminium ion equivalents for crafting functionalized amines. A second route to 39 relies on a stereoselective acetylide dianion addition to a serine-based nitrone, thereby facilitating the preparation of STX in just 14 linear steps from commercial material.