TOTAL SYNTHESIS OF CLERODANE DITERPENES

氯丹二萜的全合成

• 批准号: 3295913
• 负责人: MICHAEL J TASCHNER
• 金额: $ 7.9万
• 依托单位: UNIVERSITY OF AKRON
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3295913
• 关键词: Diels Alder reaction; antifungal agents; antiinfective agents; antiulcer drug; antiviral agents; diterpenes; drug design /synthesis /production; oxygen

The major objective of this project is to develop convergent and flexible routes for the asymmetric total syntheses of the Clerodane and the ent-Clerodane group of diterpene natural products. One of the main differences between the members of the Clerodanes is the placement or absence of oxygen functionality at the various positions of the basic skeleton. The strategy to be employed will hopefully allow access to any one of the members of these natural products by allowing for the selective introduction or removal of oxygen functionality as needed to achieve a specific goal. The Clerodanes and the ent- Clerodanes are a group of diterpenoid natural products which have been found to possess a broad spectrum of biological activity. Some have been shown to be potent insect antifeedants. Others have been found to have antitumor, antimicrobial, antifungal, antiviral, or antiulcer activity. A number of them have been isolated from plants which have been used as medicinal herbs and folk medicines. The synthetic approaches to date have followed conventional methodology for the construction of the bicyclic ring system. Our approach, which utilizes an intramolecular Diels- Alder reaction to construct a tricyclic ring system which can be unraveled to the desired bicyclic skeleton of the Clerodanes, should compliment the routes presently available. Currently, the cycloaddition controls the stereochemistry at three asymmetric centers of the final targets. It is hoped this can be extended to ultimately control the stereochemistry at five contiguous asymmetric centers not only in a relative sense but also in an absolute sense as well.

该项目的主要目标是开发汇聚和 不对称全合成的灵活路线 天然二萜的Clerodane和对位Clerodane基团 产品。成员之间的主要区别之一是 Clerodanes是指氧气的放置或缺失 基本骨骼不同位置的功能。这个 将采用的策略有望允许访问以下任何一个 这些天然产品的成员通过允许 选择性地引入或去除氧官能团，如 需要达到一个特定的目标。克莱罗丹和恩特- 十六烷是一类二萜类天然产物，具有 已被发现具有广泛的生物活性。 其中一些已经被证明是有效的昆虫拒食剂。其他 已经被发现具有抗肿瘤，抗微生物，抗真菌， 抗病毒，或抗溃疡活性。他们中的一些人已经 从被用作草药的植物中分离出来 民间医药。到目前为止，综合的方法紧随其后 双环构筑的常规方法 系统。我们的方法，利用分子内Diels- 阿尔德反应构建三环体系，该体系可以 被分解成所需的双环Clerodane骨架， 应该是对现有路线的补充。目前， 环加成反应控制着三个不对称的立体化学 最终目标的中心。希望这一点可以扩展到 最终将立体化学控制在五个连续的位置 不对称中心不仅在相对意义上，而且在 也是绝对有意义的。