Synthesis of terpenoids having unique IN-OUT skeleton and Development of their biological properties

具有独特IN-OUT骨架的萜类化合物的合成及其生物学特性的开发

• 批准号: 03640479
• 负责人: KATO Tadahiro
• 金额: $ 1.34万
• 依托单位: Science University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03640479/
• 关键词: defense substance of termite; trinervitane; verticillol; cyclization; biogenesis of trinervitanes; stable conformation; hydride shift; 生合成; バ-テシロ-ル; ラクトン形成; 脱ホルミル化反応; セコトリネルビタン; 分子内閉環反応

By the financial support of grant-in-aid for scientific research (C), the research of following two topics were projected, 1) synthesis of trinervitanes ; 2) synthesis of verticillol. After numerous amounts of unsuccessful trials, the trinervitane skeleton was constructed by our original synthetic plan. That is, allyl chloride (1) of secotrinervitane skeleton was prepared by multi-step reactions. By the action of silver perchlorate, 1 was converted to trinervitane (2) in high yield. The newly formed double bond of 2 was exclusively tetrasubstituted. 2 is a geometrical isomer of defense substance of trinervitane (3) isolated from termite soldier. Strain energy of geometrical isomers estimated by MM2 calculation revealed that 2 is the most stable among the isomers. This evidence suggests that hydride transfer to the inner trisubstituted double bond is the essential process in the biosynthesis of natural trinervitane (3) from the hypothetical progenitor (4). The hydride transfer releases the strain energy caused by sp^2 bond. The present results concerning successful synthesis of trinervitane skeleton (4) and the information about the biogenesis of trinervitane are the first achievement.Synthetic study of verticillol lead to the construction of gamma-lactone (5) via the synthetic intermediate, cyanovertecillene. The overall yield of the intermediate is still low and further improvement of the reaction conditions is needed. Development of the biological properties of all the compounds obtained in the present study remains unsolved and is the subject of future investigation.

在国家科研资助计划（C）的资助下，本项目拟开展以下两个课题的研究：1）三去甲维他烷的合成; 2）轮枝醇的合成。经过无数次的失败尝试，我们最初的合成方案构建了trinervitane骨架。也就是说，通过多步反应制备secotrinervitane骨架的烯丙基氯（1）。在高氯酸银的作用下，1高产率地转化为三去氢维生素（2）。新形成的双键2是专门的四取代。2是从白蚁兵蚁中分离的防御物质trinervitane（3）的几何异构体。通过MM 2计算得到的几何异构体的应变能表明，2是最稳定的异构体。这一证据表明，氢化物转移到内部三取代双键是从假设的祖先（4）生物合成天然trinervitane（3）的必要过程。氢化物转移释放了由sp^2键引起的应变能。本研究首次成功地合成了trinervitane骨架（4），并对trinervitane的生物成因进行了研究。通过对verticilol的合成研究，通过合成中间体cyanovertecillene，构建了γ-内酯（5）。中间体的总收率仍然较低，需要进一步改进反应条件。在本研究中获得的所有化合物的生物学特性的发展仍然没有解决，是未来调查的主题。

项目成果

"Cyclization of Epoxyneocembrene Derivatives to Secotrinervitanes" J.Org.Chem.56. 4520-4525 (1991)

“环氧新松烯衍生物环化为 Secotrinervitanes”J.Org.Chem.56。

加藤 忠弘,蛭川 俊史 並木 光治: "Selective Terminal Olefin oxidation of n-3 polyunsaturated fatty acids" Tetrahedron Letters. 33. 1475-1478 (1992)

Tadahiro Kato、Toshifumi Hirukawa、Mitsuharu Namiki：“n-3 多不饱和脂肪酸的选择性末端烯烃氧化”Tetrahedron Letters 33. 1475-1478 (1992)。

蛭川 俊史.首藤 敏之 加藤 忠弘: "Synthesis of secotrinervitane, unique bicyclic diterpene from termites" J. Chem. Soc., Perkin I. 1993. (1993)

Toshifumi Hirukawa. Toshiyuki Shuto 和 Tadahiro Kato：“白蚁中独特的双环二萜的合成”J. Chem.，Perkin I. 1993。