Synthetic and bioorganic studies on Ciguatoxin and Tetrodotoxin acting to sodium channel protein

作用于钠通道蛋白的雪卡毒素和河豚毒素的合成和生物有机研究

• 批准号: 14360063
• 负责人: ISOBE Minoru
• 金额: $ 9.47万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14360063/
• 关键词: ciguatoxin; acetylene; biscobalt-hexacarbonyl; tetrodotoxin; cyclization; regioselectivity; hydrosylilation; sodium channel

This research includes two major natural products conducting the ion current in the sodium channel protein ; thus, ciguatoxin and tetrodotoxin. Total synthesis of the latter has been accomplished by 2 routes initiated by Claisen rearrangement or Diels-Alder cycloaddition from 2 different sugar derivatives, respectively. These routes are different with respect to the key reactions, and thus both of them are quite useful for the further bioorganic studies. On the other hand, the synthetic studies on ciguatoxin has been culminated to a point of synthesizing Left segment, Right segment and their model coupling reaction by means of acetylene biscobalt-hexacarbonyl chemistry. The crytical step is the formation of F and G rings after the coupling step. We have developed an important reaction for conversion of the cobalt complex into the requisited ketone with regioselectivity. We have also established the catalytic amount of cobalt reagent to achieve 4 steps in one pot ; thus, complexation, hydrosylilation, cyclization and decomplexation with stereochemical control.

这项研究包括两个主要的天然产物进行离子电流的钠通道蛋白质;因此，雪卡毒素和河豚毒素。后者的全合成已完成2路线由Claisen重排或Diels-Alder环加成，分别从2种不同的糖衍生物。这两条路线在关键反应方面是不同的，因此这两条路线对于进一步的生物有机研究都是非常有用的。另一方面，雪卡毒素的合成研究已发展到乙炔双钴-六羰基化学合成左片段、右片段及其模型偶联反应。关键步骤是在耦合步骤之后形成F环和G环。我们开发了一个重要的反应，使钴配合物具有区域选择性地转化为所需的酮。我们还确定了钴试剂的催化量，以实现一锅法4个步骤;因此，络合，氢甲酰化，环化和解络合与立体化学控制。

项目成果

M.Isobe et al.: "Convergent Synthesis of the E'FGH'ring fragment of ciguatoxin 1B via an acetylene cobalt complex strategy"Organic Letters. 4. 1183-1186 (2002)

M.Isobe 等人：“通过乙炔钴复合物策略聚合合成雪卡毒素 1B 的 EFGH 环片段”有机快报。

M.Isobe et al.: "Mechanistic Studies on the Hydrosilylation of an Acetylene cobalt and O-Silylation"Tetrahedron. 58. 6485-6492 (2002)

M.Isobe 等人：“乙炔钴的氢化硅烷化和 O-硅烷化的机理研究”四面体。

M.Isobe et al.: "Stereoselective synthesis of the fully functionalized HIJ-ring framework of ciguatoxin."Synlett. 603-608 (2004)

M.Isobe 等人：“立体选择性合成雪卡毒素的全功能化 HIJ 环框架。”Synlett。

M.Isobe et al.: "Synthesis of the JKLM-ring fragment of ciguatoxin."Tetrahedron. 59. 6851-8805 (2003)

M.Isobe 等人：“雪卡毒素 JKLM 环片段的合成”。四面体。

M.Isobe et al.: "Different C-Glycosidation products of glucal with alkynyl or propargyl silanes under acidic conditions."Org. Lett.. 5. 4883-4885 (2003)

M.Isobe 等人：“酸性条件下葡糖与炔基或炔丙基硅烷的不同 C-糖苷化产物。”Org。