INTRAMOLECULAR CYCLOPENTENE ANNULATION

分子内环戊烯环化

• 批准号: 3070675
• 负责人: TOMAS HUDLICKY
• 金额: $ 4.94万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-09-30 至 1989-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3070675
• 关键词: alkaloids; carbopolycyclic compound; cyclic compound; cyclopentane; cyclopropanes; diene; drug design /synthesis /production; heterocyclic compounds; nitrene; pyrroles; terpenes

The proposed research addresses not only the implementation of a new and general synthetic method into the compendium of procedures available for the synthesis of complex natural products of biological significance, but also the development of some novel aspects of two reactions which were used during the former endeavor. Our strategy involves the intramolecular addition of a carbenoid, a nitrene, or any equivalent species to a conjugated diene in a 1,4-mode, at least formally, to produce ring annulated cyclopentenes or dihydropyroles. We focus on the construction of carbon skeletons containing especially any quaternary centers rather than on any final functionalizations which will be adversed later on preformed skeletons via simple differentiated functionalities in energetically feasible and practical manner. This approach avoids multi-step syntheses with intermediates containing complex substitution patterns and eliminates any protective/deprotective operations. With the above philosophy in mind we wish to investigate various topological permutations of the diene-carbenoid system to maximize the generality of the cyclopentene dihydropyrrole annulation. We intend to expand this methodology to heterocyclic compounds since we have already established the carbocyclic cyclopentene annulation as a general method of access to cyclopentanoid terpenes. Finally, we will investigate novel uses of the Simons-Smith and the Reformatsky reactions which we have used during our syntheses of terpenes and which spurred certain tangential interests to the point where both warrant independent investigations. The major aims of our projected research are as summarized: a. Continuing application of cyclopentene annulation to the synthesis of terpenes; b. Investigations of non-pyrolytic alternatives to the vinylcyclopropane rearrangement; c. Implementation of the intramolecular variant of the Simons-Smith reaction as means of novel carbon-carbon bond formation; d. Initiation of nitrene-diene additions; e. Investigation of novel uses of the Reformatsky reaction in synthesis. The overall significance of the proposed research rests in the provision of several efficient general synthetic methods which can be applied to the preparation of various medicinal agents currently in demand.

拟议的研究不仅涉及实施新的和 通用合成方法成程序简编，适用于 具有生物学意义的复杂天然产物的合成，但 还介绍了两个反应的一些新方面的发展。 在前一次努力中。我们的策略涉及分子内 将类卡宾、氮化物或任何同等物种添加到 至少在形式上以1，4-模共轭的二烯，以产生环 环状环戊烯或二氢吡咯。我们专注于建设 尤其是含有任何四元中心的碳骨架，而不是 关于任何最终的功能化，这将在以后的预演中予以说明 骨骼通过简单的差异化功能在能量上 可行、务实的态度。这种方法避免了多步合成。 具有含有复杂取代模式的中间体，并消除 任何保护/解除保护操作。牢记上述理念 我们想要研究不同的拓扑排列 二烯-类卡宾体系最大限度地提高环戊烯的通用性 二氢吡咯环化。我们打算将这一方法扩展到 杂环化合物，因为我们已经建立了碳环 环戊烯环化作为获得环戊烷的一般方法 萜类化合物。最后，我们将调查西蒙斯-史密斯的小说用法和 我们在合成过程中使用的Reformsky反应 这激发了某些切题的兴趣，以至于 这两起案件都需要进行独立调查。我们计划的主要目标是 研究总结如下：a.环戊烯的继续应用 对萜类化合物合成的环化反应；b.非热解反应的研究 乙烯基环丙烷重排的替代品；c.实施 Simons-Smith反应的分子内变体作为新的手段 碳-碳键的形成；d.引发丁二烯加成反应； 雷格茨基反应在合成中的新用途的研究。这个 拟议研究的总体意义在于提供 几种有效的通用合成方法，可应用于 目前需求量较大的各种药物制剂。