Synthetic studies of bioactive marine polycyclic ethers

生物活性海洋多环醚的合成研究

• 批准号: 15590028
• 负责人: MORI Yuji
• 金额: $ 2.24万
• 依托单位: Meijo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590028/
• 关键词: polycyclic ehter; synthesis; neurotoxin; gambierol; oxiranyl anion; diarrheic shellfish toxin; adrtiatoxin; ムール貝; ラジカル反応; テトラヒドロピラン; yessotoxin; ホタテガイ; adriatoxin; tetrahydropyan

The marine polycyclic ether toxins, associated with the massive fish kills and human food poisoning from red tides and dinoflagellates have attracted much attention in the chemistry community for their intriguing molecular structure and biological activity. In this project, synthetic studies of adriatoxin and gambierol were undertaken, and the following results were obtained.1.Synthetic studies of adriatoxin.Adriatoxin, a diarrheic shellfish toxin isolated from mussels, consists of a decacyclic polyether framework containing three sulfate esters and a side chain. The ABCDEF ring system was synthesized in a convergent manner by coupling of the A and DEF rings which were prepared based on an oxiranyl anion strategy. On the other hand, the HIJ ring fragment was constructed by oxiranyl anion chemistry and radical cyclization.2.Synthetic studies of gambierol.Gambierol is a neurotoxin isolated from the ciguatera causative dinoflagellate Gambierdiscus toxicus. The structure consists of an octacyclic polyether containing three hydroxy groups and a partially skipped triene side chain. The ABCD ring system of gambierol has synthesized in 21 synthetic transformations starting from monocyclic D ring diol. The key reactions employed were alkylation of oxiranyl anion, 6-endo cyclization, dithiane-epoxide coupling reaction, and reductive etherification.

海洋多环醚毒素因其有趣的分子结构和生物活性而引起化学界的广泛关注，它与赤潮和甲藻造成的大量鱼类死亡和人类食物中毒有关。本课题对阿霉素和甘比罗的合成进行了研究，主要结果如下：1.阿霉素的合成研究阿霉素是一种从贻贝中分离出来的贝类毒素，由一个十环聚醚骨架和一个侧链组成，骨架中含有三个硫酸酯。ABCDEF环系统是通过基于环氧乙烷阴离子策略制备的A环和DEF环的偶联以收敛方式合成的。另一方面，通过环氧乙烷阴离子化学和自由基环化反应，构建了HIJ环片段。2.甘比洛尔的合成研究甘比洛尔是从引起雪卡毒的甲藻Gambierdiscus toxicus中分离得到的一种神经毒素。该结构由含有三个羟基和部分跳过的三烯侧链的八环聚醚组成。以D环单环二醇为起始原料，经21步合成反应，得到了甘比洛尔的ABCD环系。所采用的关键反应有环氧乙烷阴离子的烷基化反应、6-内环化反应、二噻烷-环氧化合物偶联反应和还原醚化反应。

项目成果

Yuji Mori, Toyohisa Takase, Ryoji Noyori: "Iterative synthesis of the ABCDEF-ring system of yessotoxin and adriatoxin"Tetrahedron Lett.. 44・11. 2319-2322 (2003)

Yuji Mori、Toyohisa Takase、Ryoji Noyori：“虾毒素和阿德里亚毒素的 ABCDEF 环系统的迭代合成”Tetrahedron Lett.. 44・11 (2003)。

Synthesis of the ABCD Ring of Gambierol

甘比尔醇ABCD环的合成

• 发表时间: 2005
• 期刊: Organic Letters 7・18
• 作者: Hiroki Furuta;Mariko Hase;Ryoji Noyori;Yuji Mori
• 通讯作者: Yuji Mori

A stereoselective route to multi-substituted tetrahydropyrans by vinyl radical cyclization

乙烯基自由基环化制备多取代四氢吡喃的立体选择性路线

• 发表时间: 2005
• 期刊: Tetrahedron 61・36
• 作者: Naoki Hiramatsu;Natsuko Takahashi;Ryoji Noyori;Yuji Mori
• 通讯作者: Yuji Mori

Yuji Mori, Kouichi Nogami, Hisafumi hayashi, Ryoji Noyori: "Sulfonyl-stabilized Oxiranyllithium-Based Approach to Polycyclic Ethers. Convergent Synthesis of the AABCDEF-Ring System of Yessotoxin and Adriatoxin"J.Org.Chem.. 68・23. 9050-9060 (2003)

Yuji Mori、Kouichi Nogami、Hisafumi hayashi、Ryoji Noyori：“基于磺酰基稳定的环氧乙烷基锂的多环醚方法。Yessotoxin 和 Adriatoxin 的 AABCDEF 环系统的收敛合成”J.Org.Chem.. 68・23- 9060 (2003)

Hiroki Furuta, Toyohisa Takase, Hisafumi Hayashi, Ryoji Noyori, Yuji Mori: "Synthesis of trans-fused polycyclic ethers with angular methyl groups using sulfonyl-stabilized oxiranyl anions"Tetrahedron. 59・49. 9767-9777 (2003)

Hiroki Furuta、Toyohisa Takase、Hisafumi Hayashi、Ryoji Noyori、Yuji Mori：“使用磺酰基稳定的环氧乙烷基阴离子合成具有角甲基的转稠合多环醚”Tetrahedron 59・49。