Synthetic Studies of Cotylenol, Having Plant Growth Activity, and the Related Biogenetically Active Terpenoids.

具有植物生长活性的子叶烯醇和相关生物遗传活性萜类化合物的合成研究。

• 批准号: 03640475
• 负责人: KATO Nobuo
• 金额: $ 1.28万
• 依托单位: KYUSHU UNIVERSITY
• 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-03640475/
• 关键词: Terpenoid Synthesis; Formation of 8-Membered Ring; Cotylenol; Plagiospirolide; Sordaricin; Biological Diels-Alder Reaction; テルペノイド合成; 8員環形式; コチレノ-ル; 分子力場計算; 分子内DielsーAlder反応; 低原子価チタン

1. It has been proved that a diterpenoid named sordaricin (1) is biosynthesized from its congener, hydroxycycloaraneosene (2). From the structural relationships between 1 and 2, the biogenesis of 1 must involve an oxidative ring-fission of the central 8-membered ring of 2 followed by an intra-molecular Diels-Alder reaction of resulted cyclopentadiene and unsaturated aldehyde moieties. The synthetic studies utilizing of this Diels-Alder reaction have accomplished the first total synthesis of methyl ester derivative of 1.2. The total synthesis of fusicocca-2,5-diene (3), a 5-8-5-membered tricyclic diterpene, has been accomplished. Although 3 has not been isolated yet, several terpenoids are considered to be biosynthesized from 3. Plagiospilolides A and B (4,5), metabolites of the liverwort, are the Diels-Alder products from 3 and the sesquiterpene lactones, diplophyllolide (6) and diplophyllin (7), respectively. In fact, the Diels-Alder reactions between 3 and totally synthesized 6 and 7 gave 4 and 5, respectively, with high stereoselectivities. With this total synthesis, the absolute configurations of 4 and 5 have been deduced.3. A synthetic problem for the total synthesis of cotylenol (8) laid in the control of the stereochemistry of an 8,9-glycol moiety. To overcome this problem, two synthetic routes were investigated. Although the reductive cyclization of dial-precursors failed to control the stereochemistries of this glycol function, the 'ene'-cyclization procedure gave several encouraging results. The later process has provided not only the method of controlling the stereochemistries but also the method of converting 3-hydroxyl group, which is deeply related with an instability of 8, to a thiol moiety.

1.已证明一种二萜类化合物Sordaricin（1）是由其同系物羟基环蜘蛛素（2）生物合成的。从1和2之间的结构关系，1的生物成因必须涉及2的中央8元环的氧化环分裂，然后由所产生的环戊二烯和不饱和醛部分的分子内Diels-Alder反应。利用此Diels-Alder反应进行的合成研究首次完成了1.2甲酯衍生物的全合成。完成了5-8-5元三环二萜类化合物fusicocca-2，5-diene（3）的全合成。虽然3还没有被分离出来，但几种萜类化合物被认为是由3生物合成的。地钱的代谢产物斜斑螺内酯A和B（4，5）分别是3和倍半萜内酯diplophyllene（6）和diplophyllin（7）的Diels-Alder产物。事实上，3与完全合成的6和7之间的Diels-Alder反应分别得到具有高立体选择性的4和5。通过全合成，推导出了4和5的绝对构型.在Cotylenol（8）的全合成中，一个合成难题在于8，9-二醇部分的立体化学的控制。为了克服这个问题，研究了两种合成路线。虽然二醇前体的还原环化未能控制这种二醇官能团的立体化学，但“烯”环化过程给出了几个令人鼓舞的结果。后一种方法不仅提供了控制立体化学的方法，而且还提供了将与8的不稳定性密切相关的3-羟基转化为硫醇部分的方法。

项目成果

Nobuo KATO et al.: "The Biomimetic Construction of Sordaricin Skeletone from a B-seco-cycloaraneosene Derivative" Chemistry Express. 6. 687-690 (1991)

Nobuo KATO 等人：“从 B-seco-环芳烯衍生物仿生构建 Sordaricin 骨架”Chemistry Express。

Nobuo KATO,Xue WU,Hideyuki NISHIKAWA,and Hitoshi TAKESHITA: "Stereocontrolled Synthesis of Optically-Active Plagiospirolides A and B" SYNLETT.

Nobuo KATO、Xue WU、Hideyuki NISHIKAWA 和 Hitoshi TAKESHITA：“光学活性斜螺内酯 A 和 B 的立体控制合成”SYNLETT。

Nobuo KATO et al.: "Stereocontrolied Synthesis of Optically-Active Plagiospirolides A and B" SYNLETT.

Nobuo KATO 等人：“光学活性斜螺内酯 A 和 B 的立体控制合成”SYNLETT。

Nobuo KATO et al.: "Total Synthesis of Sordaricin Methyl Ester and Its Δ^2-Derivative" J.Chem.Soc.Chem.Commun.

Nobuo KATO 等人：“Sordaricin 甲酯及其 Δ^2-衍生物的全合成”J.Chem.Soc.Chem.Commun。

Nobuo KATO,Xue WU,and Hitoshi TAKESHITA: "Total Synthesis of 5-8-5-Membered Tricyclic Terpenoids" J.Syn.Org.Chem.Jpn.50. 563-571 (1992)

Nobuo KATO、Xue WU 和 Hitoshi TAKESHITA：“5-8-5 元三环萜类化合物的全合成”J.Syn.Org.Chem.Jpn.50。