CORIOLIN AND OTHER TRIQUINANE SESQUITERPENES

科里奥林和其他三喹啉倍半萜

• 批准号: 3129142
• 负责人: TOMAS HUDLICKY
• 金额: $ 10.49万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-07-01 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3129142
• 关键词: antineoplastic antibiotics; chemical addition; chemical reaction; chemical structure function; chemical synthesis; cyclopentane; high performance liquid chromatography; nuclear magnetic resonance spectroscopy; sesquiterpenes; stereochemistry

This proposal addresses the general method of preparation of linear and nonlinear triquinane serquiterpanes, in particular several biologically active coriolins and hirsuitic acids. Our proposed syntheses represent newly redesigned versions of the original research propositions funded in 1981. The new approach is perhaps more flexible in the ultimate obtention of the natural products for medicinal screening. The continuous supply of especially the antitumor and antibiotic coriolins from natural sources seems uncertain and, therefore, it is essential that an efficient and a general preparation of these compounds be available. Our synthetic plan thus focuses on the rapid production of a flexible tricyclic intermediate which is equipped with properly differentiated functionalities to permit its conversion into various coriolin natural products. This intermediate is accessible through the application of intramolecular cyclopentene annulation methodology which has been developed in our laboratory and pursued in conjunction with terpene synethesis. Following our recent work on the synthesis if triquinanes we propose to concentrate our efforts on the specific aims summarized below: a. Synthesis of five coriolins and three hirsutic acids by a redesigned strategy. b. Synthesis of other linear and nonlinear triquinanes of medicinal interest by an extension of our methodology. c. Investigation of the ulity of the intramolecular Simmons-Smith reaction and sequential radical alkylation of dienic dihalides as alternatives to methods utilizing diazoketones for cyclopropanations and d. Explorations of some newly discovered aspects of the Reformatsky reaction of halocrotonates in organic synthesis. The overall significance of the proposed research lies not only in the provision of the biologically important target compounds but also in the development of what appears to be a quite general system-oriented design of cyclopentanoid terpenes. The pursuit of the novel application of the two established reactions will enrich the compendium of the methods available for the carbon-carrbon bond formation. The budgetary period of this applications has been expanded to five years in order to further utilize the Cyclopentene Annualtion Methodology in the synthesis of biologically active cyclopentanoid terpenes and to begin detailed investigations of several new and potentially general synthetic methods.

该提案涉及制备线性和 非线性三奎烷司奎萜，特别是几种生物学上的 活性科里林和山梨酸。 我们提出的合成代表 新设计的原始研究命题的版本 1981.新的方法在最终的获得上或许更加灵活 用于药物筛选的天然产物。 持续供应 尤其是天然来源的抗肿瘤和抗生素科里林 似乎是不确定的，因此，有必要建立一个高效且 这些化合物的一般制备方法是可用的。 因此，我们的综合计划侧重于快速生产灵活的 三环中间体，配备有适当分化的 允许其转化为各种天然科里林的功能 产品。 该中间体可通过应用程序访问 已开发的分子内环戊烯成环方法 在我们的实验室中并与萜烯合成结合进行。 根据我们最近对三奎烷的合成工作，我们建议 我们将努力集中于下列具体目标： 一个。 通过重新设计合成五种科里林和三种毛酸 战略。 b. 其他线性和非线性药用三奎烷的合成 通过扩展我们的方法来产生兴趣。 c. 分子内Simmons-Smith反应的有效性研究 和二烯二卤化物的连续自由基烷基化作为替代品 利用重氮酮进行环丙烷化的方法和 d. 对Reformatsky一些新发现方面的探索 有机合成中卤代巴豆酸酯的反应。 本研究的总体意义不仅在于 提供生物学上重要的目标化合物，而且还可以 开发看起来相当通用的面向系统的设计 环戊烷类萜烯。 追求两者的新颖应用 已建立的反应将丰富可用方法的纲要 用于碳-碳键的形成。 该申请的预算期限已延长至五年 为了进一步利用环戊烯年化方法 合成具有生物活性的环戊烷萜烯并开始 对几种新的和潜在的通用合成的详细研究 方法。