INTRAMOLECULAR CYCLOPENTENE ANNULATION

分子内环戊烯环化

• 批准号: 3070674
• 负责人: TOMAS HUDLICKY
• 金额: $ 5.15万
• 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/3070674
• 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一项新的 将一般合成方法纳入可用于 具有生物学意义的复杂天然产物的合成， 还发展了两个反应的一些新的方面， 在前一个奋进。 我们的策略包括分子内 将类卡宾、氮宾或任何等同物质加成到 共轭二烯在1，4-模式，至少形式上，以产生环 环状环戊烯或二氢吡咯。 我们专注于建设 碳骨架，特别是含有任何四元中心，而不是 任何最终的功能化，这将是反对后，对预制 骨架通过简单的分化功能， 切实可行的方式。 这种方法避免了多步合成 含有复杂取代模式的中间体， 任何保护/去保护操作。 考虑到上述哲学 我们希望调查各种拓扑排列的 二烯-类卡宾体系以使环戊烯的通用性最大化 二氢吡咯成环。 我们打算扩大这一方法， 杂环化合物，因为我们已经建立了碳环 环戊烯成环作为获得环戊烷类化合物的一般方法 萜烯。 最后，我们将研究西蒙斯-史密斯的新颖用途， 我们在合成下列化合物的过程中使用的Reformatsky反应： 萜烯，并刺激了某些切线利益的点， 两者都值得进行独立调查。 我们计划的主要目标是 研究结果如下：a.环戊烯的继续应用 环化至萜烯的合成; B.非热解研究 乙烯基环丙烷重排的替代物; c.执行 Simons-Smith反应的分子内变体作为新的 碳-碳键形成; d.引发氮烯-二烯加成; e. 研究Reformatsky反应在合成中的新用途。 的 拟议研究的总体意义在于提供 介绍了几种有效的通用合成方法， 目前需要的各种药剂的制备。