Development of Efficient Methods for the Synthesis of Polycyclic Ethers

多环醚合成有效方法的开发

• 批准号: 11672135
• 负责人: NAKATA Tadashi
• 金额: $ 2.5万
• 依托单位: The Institute of Physical and Chemical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11672135/
• 关键词: Brevetoxin; Polycyclic ether; Samarium diiodide; Tetrahydropyran; Oxepane; Convergent synthesis; Two-directional synthesis; Iterative synthesis; 4環性エーテル; ブレベトキシンB; 海洋産多環状エーテル; 環化反応; トランス縮環; アルコキシアクリレート

Since the first isolation of brevetoxin B, a neurotoxin produced by the red tide organism Gymnodinium breve, many marine polycyclic ethers of this type have been reported. The most characteristic structural feature of these natural products is trans-fused polycyclic ether ring system. The synthetically challenging unique structures and their potent biological activities have attracted the attention of numerous synthetic organic chemists.In this project, we have developed an extremely facile and highly efficient strategy for the iterative synthesis of a trans-fused polytetrahydropyran ring system based on the SmI_2-induced reductive intramolecular cyclization. This method is also effective for the synthesis of polycyclic ether ring systems including oxepane and also an angular methyl group. Based on the present SmI_2-induced cyclization, a strategy for two directional synthesis of polycyclic ether was developed.A very efficient convergent strategy for the construction of the trans-fused 6-6-6-6-membered tetracyclic ether ring system was developed based on the acetylide-triflate coupling of two tetrahydropyrans, oxidation of the alkyne group to an a-diketone, double cyclization to 6,6,6,6-membered tetracyclic diacetal, and stereoselective reduction of the diacetal with Et_3SiH-TMSOTf.In conclusion, we have developed very simple and efficient strategies for the construction of trans-fused polycyclic cyclic ether ring system. This strategy would be widely applicable to efficient syntheses of natural polycyclic ethers

自第一次从赤潮生物短裸藻中分离出短裸藻毒素B以来，已报道了许多这类海洋多环醚。这些天然产物最具特色的结构特征是多环醚环系统。本课题基于SmI_2诱导的还原性分子内环化反应，发展了一种简便、高效的迭代合成方法，合成了一种具有独特结构和生物活性的反式聚四氢吡喃环体系。该方法对于合成包括氧杂环庚烷和角甲基的多环醚环体系也是有效的。在SmI 2诱导的环化反应的基础上，发展了一种双向合成多环醚的策略，通过两个四氢吡喃的乙炔基-三氟甲磺酸酯偶联，炔基氧化成α-二酮，双环化成6，6，6，6元四环二缩醛的合成，以及用Et_3SiH-TMSOTf对该二缩醛的立体选择性还原，从而发展了一种非常简单有效的反式稠合多环醚环体系的构建策略。这一策略可广泛应用于天然多环醚的高效合成

项目成果

G.Matsuo: "Efficient Convergent Synthesis of a Trans-fused 6-6-6-6-Membered Tetracyclic Ether Ring System."Tetrahedron Lett.. 41. 903-906 (2000)

G.Matsuo：“反式稠合 6-6-6-6 元四环醚环系统的高效收敛合成”。Tetrahedron Lett.. 41. 903-906 (2000)

G.Matsuo: "Synthetic studies on brevetoxin-B.1.Stereoselective synthesis of the ABC-ring system."Tetrahedron Lett.. 41. 7673-7676 (2000)

G.Matsuo：“短链毒素-B.1 的合成研究。ABC 环系统的立体选择性合成。”Tetrahedron Lett.. 41. 7673-7676 (2000)

H.Matsukura: "Synthetic studies on brevetoxin-B.3. Stereoselective synthesis of the IJK-ring system."Tetrahedron Lett.. 41. 7681-7684 (2000)

H.Matsukura：“短链毒素-B.3 的合成研究。IJK 环系统的立体选择性合成。”Tetrahedron Lett.. 41. 7681-7684 (2000)

H.Matsukura: "Synthetic studies on brevetoxin-B.3.Stereoselective synthesis of the IJK-ring system."Tetrahedron Lett.. 41. 7681-7684 (2000)

H.Matsukura：“短链毒素-B.3 的合成研究。IJK 环系统的立体选择性合成。”Tetrahedron Lett.. 41. 7681-7684 (2000)

N.Hori: "An Efficient Strategy for the Iterative Synthesis of a trans-Fused Polytetrahydropyran Ring System via SmI_2-Induced Reductive Intramolecular Cyclization."Tetrahedron Lett.. 40. 2811-2814 (1999)

N.Hori：“通过 SmI_2 诱导的还原分子内环化迭代合成反式稠合聚四氢吡喃环系统的有效策略。”Tetrahedron Lett.. 40. 2811-2814 (1999)