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Synthesis of Polycylic Compounds Possessing Biological Activities by Novel Intramolecular Cascade Reactions

通过新型分子内级联反应合成具有生物活性的多环化合物

基本信息

批准号：
09672136
负责人：
IHARA Masataka
金额：
$ 2.18万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

Cascade reactions forming multiple bonds in a stereo- and regio-selective manner by one procedure is one of the most ideal process in organic synthesis. The cascade reaction is also called as domino and tandem reaction. We have already developed two types of cascade reactions, which are useful for natural products synthesis. Thus, the intramolecular double Michael reaction of a compound having two types of unsaturated carbonyl groups provides a ploycyclic compound fused to six membered ring possessing five stereogenic centers. On the other hand, the intramolecular Michael-aldol reaction of the keto unsaturated ester constructs a polycyclic ring system fused to four membered ring having four stereogenic centers. These cascade reactions could be carried out under five different conditions using lithium hexamethyldisilazide or combinations of Lewis acids and Lewis amines. They have various advantages due to both merits of intramolecular reaction and cascade reaction. In this project, we achieved following total syntheses of natural products possessing important biological(1) Synthesis of Indole Alkaloid, TacamonineTreatment of an indole derivative having an alpha, beta-unsaturated ester function at the C-2 position and an unsaturated amide group at the C-3 position with TBSOTf in the presence of triethylamine provided the indoloquinolizidine derivative. Synthesis of tacamonine was carried out in a facile manner from the product.(2) Synthesis of Sesquiterpenoids, Cedranediol and CedranoxideIntramolecular double Michael reaction of 5-substituted cyclopentenone gave tricyclo[5.2.1 .0^<1.5>]decane, which was converted into cedranediol and cedranoxide.(3) Synthesis of Sesquiterpenoid, CulmorineAn effective total synthesis of culmorine was accomplished via the intramolecular double Michael reaction of 4-substituted cyclopentenone as key step.

级联反应是有机合成中最理想的方法之一，它通过一个步骤以立体和区域选择性的方式形成多个键。级联反应也称为多米诺骨牌和串联反应。我们已经开发了两种类型的级联反应，这是有用的天然产物的合成。因此，具有两种类型的不饱和羰基的化合物的分子内双迈克尔反应提供稠合至具有五个立体中心的六元环的多环化合物。另一方面，酮不饱和酯的分子内Michael-aldol反应构建了稠合到具有四个立体中心的四元环的多环体系。这些级联反应可以在五种不同的条件下使用六甲基二硅基氨基锂或刘易斯酸和刘易斯胺的组合进行。由于分子内反应和级联反应的优点，它们具有各种优点。在本项目中，我们实现了以下具有重要生物活性的天然产物的全合成（1）吲哚生物碱、塔卡莫宁的合成在三乙胺的存在下，用TBSOTf处理在C-2位具有α，β-不饱和酯官能基和在C-3位具有不饱和酰胺基的吲哚衍生物，得到吲哚并喹啉嗪衍生物。以简便的方式由产物合成他卡莫司。(2)倍半萜类化合物、雪松烷醇和雪松氧化物的合成5-取代环戊烯酮经分子内双Michael反应生成三环[5.2.1.0 ^<1.5>]癸烷，再经转化生成雪松烷醇和雪松氧化物。(3)以4-取代环戊烯酮的分子内双Michael反应为关键步骤，实现了香青碱的有效全合成。