STEREOCONTROLLED [M+N] ANNULATION REACTIONS

本提案中概述的研究的主要目标是 发展一般的立体控制环化方法， 高度官能化的七元和八元环。 容易 可访问的转换器被设计为允许转换为 具有不同取代模式的碳环和杂环， 立体化学 立体化学和区域化学的控制是 通过一种新的机制途径建立， 可预测性和可靠性。 这使得前所未有的控制， 将无环碳负离子转化为重要的碳环， 杂环 在新的合成方法的开发方面，将有几个领域 探讨了 用于片段化双环醚亚基的程序 将研究在成环过程中最初产生的。 将该方法扩展到双环胺的合成也将 接受检查。 如果成功，该方法将对 托品烷类生物碱及含五元和五元生物碱的合成 六元环氮杂环。 其他基础研究 这可能会导致重大的新领域的研究。 这个程序的一个自然演变是应用这些新的 复杂有机分子的合成方法。 提出了可供选择的目标结构， 为了证明这些合成物的价值， 方法. 包括的方法， Eunicellin/cladiellin/asbestinin类二萜，其具有 在健康相关领域尤为重要。 建议由 通过环化策略可以进入Eunicellin环系统 在这个建议中概述，导致硬植素B的合成。 最后，探讨了“in-out”桥连双环骨架的结构， 巨大戟醇药效团。

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.