CORIOLIN AND OTHER TRIQUINANE SESQUITERPENES

科里奥林和其他三喹啉倍半萜

• 批准号: 3129144
• 负责人: TOMAS HUDLICKY
• 金额: $ 12.23万
• 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/3129144
• 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.

本建议介绍了制备线型和线型的一般方法。 非线性三喹烷倍半萜烷，特别是几种生物上的 活性科里奥林和水苏酸。我们建议的合成方法代表了 资助的原始研究命题的新重新设计版本 1981年。新的方法也许在最终的观察中更加灵活。 用于药物筛选的天然产品。持续不断的供应 尤其是天然来源的抗肿瘤和抗生素珊瑚油素 似乎是不确定的，因此，一个有效和 这些化合物的一般制备是可用的。 因此，我们的综合计划侧重于快速生产灵活的 配备有适当区分的三环中间体 允许将其转化为各种天然科里林的功能 产品。此中间件可通过应用 已开发的分子内环戊烯环化方法 在我们的实验室进行，并结合萜烯合成进行研究。 根据我们最近在合成IF三喹烷方面的工作，我们建议 将我们的努力集中在以下具体目标上： A.用重新设计的方法合成五个科里奥林和三个多毛酸 策略。 其他线性和非线性药物三喹烷类化合物的合成 对我们方法的扩展感兴趣。 C.分子内Simmons-Smith反应的有序性研究 和二烯二卤化物的顺序自由基烷基化作为替代 方法利用重氮酮进行环丙烷化反应和 D.探索新发现的ReFormatsky的一些方面 卤代碳酸酯在有机合成中的反应。 拟议研究的总体意义不仅在于 提供具有生物重要性的目标化合物，但也在 开发看似相当通用的面向系统的设计 环戊烷类萜类化合物。追求二者的新颖应用 已建立的反应将丰富现有方法的概要 用于碳-碳键的形成。 这项申请的预算期已延长至五年 为了进一步利用环戊烯环化方法学 生物活性环戊烷类萜类化合物的合成及开始 几种新的和潜在的通用合成材料的详细研究 方法：研究方法。

项目成果

General method of synthesis for natural long-chain beta-diketones.

天然长链β-二酮的一般合成方法。

• DOI: 10.1021/np50052a012
• 发表时间: 1987
• 期刊: Journal of natural products
• 影响因子: 5.1
• 作者: Barbieri,G;Seoane,G;Trabazo,JL;Riva,A;Umpierrez,F;Radesca,L;Tubio,R;Kwart,LD;Hudlicky,T
• 通讯作者: Hudlicky,T