TOTAL SYNTHESIS OF CLERODANE DITERPENES

氯丹二萜的全合成

• 批准号: 3295910
• 负责人: MICHAEL J TASCHNER
• 金额: $ 10.69万
• 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 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3295910
• 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发展趋同和 不对称全合成的灵活路线 氯罗烷和对映-氯罗烷族二萜天然产物 产品. 成员之间的主要区别之一 克莱罗丹是氧气的放置或缺乏 在基本骨架的各个位置上的功能。 的 将采用的战略将有希望允许进入任何一个 这些天然产物的成员，允许 选择性引入或除去氧官能团， 需要达到一个特定的目标。 克罗丹人和恩- 克罗烷是一类二萜类天然产物， 被发现具有广泛的生物活性。 有些已被证明是有效的昆虫拒食剂。 别人 已经发现具有抗肿瘤，抗微生物，抗真菌， 抗病毒或抗溃疡活性。 他们中的一些人 分离自用作草药的植物， 民间药物 迄今为止， 构建双环的常规方法 系统 我们的方法，利用分子内狄尔斯- 通过桤木反应构建三环环体系， 解开为所需的克罗烷双环骨架， 应该能补充现有的路线 目前 环加成控制了三个不对称的立体化学， 最终目标的中心。 希望这可以扩大到 最终将立体化学控制在五个相邻的 不对称中心不仅在相对意义上，而且在 绝对的感觉也是。