Complete Structure Elucidation of Maitotoxin

麦芽毒素的完整结构解析

• 批准号: 06453211
• 负责人: MURATA Michio
• 金额: $ 3.07万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06453211/
• 关键词: maitotoxin; marine natural products; polyether; dinoflagellate; NMR; spin coupling constants; stereoselective synthesis; absolute stereochemistry; 立体選択的合成; 超活性; NMR分光学

Maitotoxin is the most toxic and largest natural product among non-biopolymers known to date. Althought most of stereogenic centers in ring systems was assigned by simple NOE experiments, the complete structural elucidation was hampered by the presence of asymmetric centers in acyclic portions, particularly, C1-C14 and C134-C142 side chains. The present study has successfully elucidated the total sturcture by menas of NMR spectroscopy coupled with stereoselective synthesis of the fragmental structures. In the NMR analysis, we focused on the carbon-proton copling constants, which provided important dihedral angles for the conformational and configurational assignments of the side chains. The absolute stereochemistry has been also assigned by the synthesis of all the possible stereoisomer for fragment C,which was generated by periodate degradation of maitotoxin.

Maitotoxin是迄今为止已知的非生物聚合物中毒性最大和最大的天然产物。尽管环体系中的大部分立体中心可以通过简单的NOE实验来确定，但由于非环部分，特别是C1-C14和C134-C142侧链中存在不对称中心，阻碍了完整的结构解析。本研究成功地阐明了总结构的核磁共振波谱结合立体选择性合成的碎片结构。在核磁共振分析中，我们着重于碳-质子耦合常数，它提供了重要的二面角的构象和构型分配的侧链。绝对的立体化学也已指定的所有可能的立体异构体的合成片段C，这是由高碘酸盐降解的maitotoxin。

项目成果

Nobuaki Matsumori: "Long-range carbon-proton coupling constants for stereochemical assignment of acyclic atructures in natural products: configuration of the C5-C9 portion of maitotoxin" Tetrahedron Letters. 37. 1269-1272 (1996)

Nobuaki Matsumori：“天然产物中无环结构立体化学分配的长程碳-质子偶联常数：麦毒毒素 C5-C9 部分的配置”四面体快报。

Makoto Sasaki: "Synthesis and Stereochemical Confirmation of the cis-Fused L/M.N/O Rings of Maitotoxin" Tetrahedron Letters. 35. 5023-5026 (1994)

Makoto Sasaki：“麦毒毒素顺式稠合 L/M.N/O 环的合成和立体化学确认”四面体字母。

Nobuaki Matsumori: "Long-range carbon-proton coupling constants for stereochemical assignment of acyclic structures in natural products : configuration of the C5-C9 portion of maitotoxin." Tetrahedron Lett.37. 1269-1272 (1996)

Nobuaki Matsumori：“天然产物中无环结构立体化学分配的长程碳-质子偶联常数：麦芽毒素 C5-C9 部分的构型。”

Makoto Sasaki: "Synthetic approach toward complete struiture determnation of maitotoxin" Tetrahedron Letters. 36. 9007-9010 (1995)

Makoto Sasaki：“完整测定麦毒毒素结构的合成方法”四面体快报。

Michio Murata: "Structure and partial stereochemical assignments for maitotoxin, the most toxic and largest natural non-biopolymer." J.Am.Chem.Soc. 116. 7098-7107 (1994)

Michio Murata：“麦芽毒素的结构和部分立体化学分配，麦芽毒素是毒性最大、最大的天然非生物聚合物。”