Synthetic studies of polycyclic ether marine toxins

多环醚海洋毒素的合成研究

• 批准号: 12672074
• 负责人: MORI Yuji
• 金额: $ 2.11万
• 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: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12672074/
• 关键词: oxiranyl anion; polycylic ether; marine toxin; yessotoxin; tetrahydropyran; diarrheic shellfish poisoning; synthesis; yessotoxin; オキシラニルアニオン; トリエチルシラン; エリスリトール; エッソトキシン; 1,2-ジケトン; アセチレン; ジヘミケタール; 還元

Polycyclic ether marine toxins have interesting biological activities, such as neurotoxicity, diarrheic toxicity, and antifungal activity. In this project, synthetic studies of yessotoxin and adriatoxin, causative toxins of diarrheic shellfish poisoning were undertaken, and the following results were obtained.1. Convergent synthesis of 6-membered polycyclic ethersTwo 6-membered ethers were coupled with an acetylene unit, and the triple bond of the product was oxidized with ruthenium tetroxide to give a 1,2-diketone. The diketone was transformed into bis(methyl hemiketal) by treatment with an acid, which was then reduced with triethylsilane in the presence of TMS-triflate to give a tetracyclic polytetrahydropyran.2. Synthesis of the BCDE-ring system of yessotoxinSynthesis of a 6-6-6-7 tetracyclic polyether ring system was accomplished by starting from 6- and 7-membered ether rings and an acetylene unit by employing the convergent method stated above.3. Convergent synthesis of the ABCDEF-ring of yessotoxin and adriatoxinThe A-ring fragment with an acetylene side chain and the DEF-ring fragment with a trifluoromethanesulfonyl group on the D-ring were prepared based on an strategy of alkylation of an oxiranyl anion followed by 6-endocyclization. The synthesis of the ABCDEF-ring fragment of yessotoxin has achieved by coupling of both fragments, oxidation of the acetylene moiety to 1,2-diketone, bis(methyl acetyl) formation, and reduction.

多环醚类海洋毒素具有重要的生物活性，如神经毒性、组织毒性和抗真菌活性。本项目对引起贝类中毒的虾夷扇贝毒素和阿霉素进行了合成研究，取得了以下研究成果.六元多环醚的会聚合成两个六元多环醚与一个乙炔单元偶联，产物的三键用四氧化钌氧化得到1，2-二酮。通过用酸处理将二酮转化为双（甲基半缩酮），然后在TMS-三氟甲磺酸酯的存在下用三乙基硅烷还原，得到四环聚四氢吡喃。6-6-6-7四环聚醚环系的合成是通过使用上述收敛方法从6-和7-元醚环和乙炔单元开始完成的。蝎毒素和阿霉素ABCDEF环的收敛合成基于环氧乙烷阴离子烷基化然后6-内环化的策略，制备了具有乙炔侧链的A环片段和D环上具有三氟甲磺酰基的DEF环片段。通过偶联两个片段，乙炔部分氧化成1，2-二酮，双（甲基乙酰基）形成和还原，合成了耶索毒素的ABCDEF环片段。

项目成果

Yuji Mori: "Iterative synthesis of the ABCDEF-ring system of yessotoxin and adriatoxin"TetrahedronLetters. (印刷中). (2003)

Yuji Mori：“虾毒素和阿德里亚毒素的 ABCDEF 环系统的迭代合成”Tetrahedron Letters（出版中）。

Yuji Mori: "Synthetic studies of yessotoxin, a polycyclic ether implicated in diarrhetic shellfish poisoning : convergent synthesis of the BCDE ring system via an alkyne intermediate"Tetrahedron. 58・10. 1789-1797 (2002)

Yuji Mori：“与腹泻性贝类中毒有关的多环醚类毒素的合成研究：通过炔中间体的 BCDE 环系统的聚合合成”Tetrahedron 58・10（2002）。

Yuji Mori: "Iterative synthesis of the ABCDEF-ring system of yessotoxin and adriatoxin"Tetrahedron Lett.. in press.

Yuji Mori：“虾毒素和阿德里亚毒素的 ABCDEF 环系统的迭代合成”Tetrahedron Lett.. 正在出版。

桑嶋功ら 編(分担執筆): "生物活性天然物の合成"東京化学同人. 162 (2000)

桑岛功等编（合着）：“生物活性天然产物的合成”东京化学同人162（2000）。

Yuji Mori: "Practical synthesis of 1,3-O-di-tert-butylsilylene-protected D- and L-erythritols as a four-carbon chiral building block"J. Org. Chem.. 66-25. 8666-8668 (2001)

Yuji Mori：“1,3-O-二叔丁基亚甲硅基保护的 D-和 L-赤藓糖醇作为四碳手性结构单元的实际合成”J。