CORIOLIN AND OTHER TRIQUINANE SESQUITERPENES

科里奥林和其他三喹啉倍半萜

• 批准号: 3129141
• 负责人: TOMAS HUDLICKY
• 金额: $ 11.98万
• 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 1986-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3129141
• 关键词: antineoplastic antibiotics; chemical addition; chemical reaction; 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聚合物的一般方法。 非线性三喹烷类蛇曲萜烷，特别是几种生物活性的 活性柯黎素和多毛酸。 我们提出的合成方法代表了 新的重新设计的版本的原始研究命题资助， 1981. 新的方法在最终获得 用于药物筛选的天然产物。 不断供 特别是来自天然来源的抗肿瘤和抗生素柯黎素 似乎是不确定的，因此，至关重要的是，一个有效的和 这些化合物的一般制备是可获得的。 因此，我们的综合计划侧重于快速生产灵活的 三环中间体，其配备有适当分化的 功能，以允许其转化为各种天然科里奥利素 产品. 该中间体可通过应用 已开发的分子内环戊烯成环方法 在我们的实验室和追求与萜烯合成。 根据我们最近在合成三喹烷方面的工作，我们建议： 集中努力实现下列具体目标： a. 合成五种柯黎素和三种多毛酸的新方法 战略 B. 其他线性和非线性三喹酮类药物的合成 对我们方法扩展感兴趣。 C. 分子内Simmons-Smith反应极限的研究 和二烯二卤化物的连续自由基烷基化作为 利用重氮酮进行环丙烷化的方法， D. 探索Reformatsky的一些新发现的方面 卤代巴豆酸酯在有机合成中的反应。 所提出的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， 开发似乎是一个相当普遍的面向系统的设计， 环戊烷萜类。 追求新奇的应用两不误 已建立的反应将丰富现有方法的概要 形成碳-碳键。 这些申请的预算期已延长至五年 为了进一步利用环戊烯年化方法， 生物活性环戊烷萜类化合物合成，并开始 详细研究了几种新的和潜在的一般合成 方法.