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

在科学研究助学金(C)的资助下，计划开展以下两个课题的研究：1)三维酮类化合物的合成；2)轮枝菌素的合成。在无数次不成功的试验后，我们按照最初的合成计划构建了三维他命骨架。也就是说，通过多步反应合成了环三氢呋喃骨架的烯丙基氯(1)。在高氯酸银的作用下，1高产率地转化为三氢维生素A(2)。2的新形成的双键是完全四取代的。2是从白蚁士兵中分离得到的三维他烷(3)防御物质的几何异构体。由MM2计算得到的几何异构体的应变能表明，2是最稳定的。这一证据表明，氢化物向内三取代双键的转移是从假想的前体(4)生物合成天然三维烷(3)的基本过程。氢化物转移释放了由sp^2键引起的应变能。目前关于三环维生素A骨架(4)的成功合成和三环维生素A的生物发生的信息是第一次实现的。轮替米洛的合成研究导致了通过合成中间体氰基过铁烯合成伽马-内酯(5)。该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，是未来研究的主题。

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.