STEREOCONTROLLED [M+N] ANNULATION REACTIONS

这项提案中概述的研究的主要目标是 制定一般的、立体控制的节育术方法 高度功能化的七元环和八元环。易如反掌 可访问的合成子已被设计为允许转换为 具有不同取代方式的碳环和杂环以及 立体化学。立体化学和区域化学的控制 由一种新的机械途径建立，它具有高 可预测性和可靠性。这允许前所未有的对 非环合成子转化为重要的碳环和 杂环化合物。 在新的合成方法开发方面，将有几个领域 探索过了。双环醚亚基的裂解程序 将对环化过程中最初产生的气体进行调查。 将该方法扩展到双环胺的合成也将是可行的 接受检查。如果成功，该方法将对 托烷生物碱及含5-和-的生物碱的合成 六元环氮杂环化合物。其他基础性研究 这可能会带来重要的新的研究领域。 该程序的一个自然演变是应用了这些新的 合成方法要合成复杂的有机分子。 提出了具有挑战性的目标结构，这将是 为了展示这些合成材料的价值而建造的 方法：研究方法。其中包括以下方法： 二萜类二萜类化合物，其具有 在与健康相关的领域尤其重要。有人建议， Eunicellin环系统可以通过环化策略来接入 在本提案中概述，导致了硬藻素B的合成。 最后，对“输入-输出”桥式双环骨架进行了探讨 提出了吲哚类药物载体的概念。

The primary goal of research outlined in this proposal is the development of general, stereocontrolled annulation approaches to highly functionalized seven- and eight-membered rings. Readily accessible synthons have been designed to allow conversion to carbocycles and heterocycles bearing different substitution patterns and stereochemistries. Control of stereochemistry and regiochemistry is established by a novel mechanistic pathway which has high predictability and reliability. This permits unprecedented control in conversion of acyclic synthons to important carbocycles and heterocycles. In terms of new synthetic methods development, several areas will be explored. Procedures for fragmenting the bicyclic ether subunit initially generated in the annulation process will be investigated. Extension of the method to the synthesis of bicyclic amines will also be examined. If successful, the method would have implications in the synthesis of tropane alkaloids as well alkaloids containing five- and six-membered ring nitrogen heterocycles. Other fundamental studies are described which may lead to significant new areas for study. A natural evolution of this program is the application of these new synthetic methods to the synthesis of complex organic molecules. Challenging target structures have been put forward which will be constructed in order to demonstrate the value of these synthetic methods. Included are approaches to the eunicellin/cladiellin/asbestinin class of diterpenes, which possess particular importance in health related fields. It is suggested that the eunicellin ring system may be accessed by the annulation strategy outlined in this proposal, leading to a synthesis of sclerophytin B. Finally, an approach to the "in-out" bridged bicyclic skeleton of ingenol pharmacophores is proposed.