Application of Cascade Processes for the Synthesis of Polycyclic Ring Systems

级联工艺在多环体系合成中的应用

• 批准号: 0742663
• 负责人: Albert Padwa
• 金额: $ 45.5万
• 依托单位: Emory University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-01-15 至 2010-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0742663&HistoricalAwards=false
• 关键词: Application; Cascade; Processes; Synthesis; Polycyclic

The project will make use of novel cascade sequences for the assemblage of complex target molecules. One of the immediate goals is to develop a new approach toward piperidine synthesis that employs a tandem reaction sequence using various oximes with 2,3-bis(phenylsulfonyl)-1,3-diene. Formation of an aza-oxabicyclic ring cycloadduct involves conjugate addition of the oxime onto the diene to give a transient nitrone which then undergoes a subsequent intramolecular dipolar cycloaddition reaction. The research goals also call for a formal synthesis of the novel marine alkaloid halichlorine using a related series of reactions. The intramolecular Diels-Alder cycloaddition/rearrangement cascade of 2-amido substituted furans represents a very effective strategy for the preparation of a variety of naturally occurring alkaloids. As part of the project, the preparation of the Strychnos pentacyclic framework will be studied using this cascade approach. Another goal will be to explore the synthetic power of the tandem cyclization/cycloaddition sequence of rhodium carbenoids toward the synthesis of several Vinca alkaloids. Examination of the cyclization reaction using several alpha-diazo substituted beta-carbolines as well as its application toward the Vinca alkaloid family, including the synthesis of tacamine and vincarodine, will be undertaken. With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Albert Padwa of the Department of Chemistry at Emory University. Professor Padwa's research efforts revolve around the use of novel cascade sequences for the assemblage of complex target molecules often used in the production of new drugs and agricultural compounds. The research outlined in the proposal also represents ideal training for undergraduate, graduate and postdoctoral students, which is in keeping with NSF's goals of research and education. Students trained during the performance of this research will use this knowledge to make important future contributions in pharmaceutical research.

该项目将利用新颖的级联序列来组装复杂的目标分子。 近期目标之一是开发一种哌啶合成的新方法，该方法采用使用各种肟与 2,3-双（苯磺酰基）-1,3-二烯的串联反应序列。 氮杂双环环加成物的形成涉及肟与二烯的共轭加成，得到瞬时硝酮，然后进行随后的分子内偶极环加成反应。 研究目标还要求利用一系列相关反应正式合成新型海洋生物碱卤氯。 2-酰胺基取代呋喃的分子内狄尔斯-阿尔德环加成/重排级联代表了制备多种天然存在的生物碱的非常有效的策略。 作为该项目的一部分，将使用这种级联方法研究马钱五环框架的制备。 另一个目标是探索铑类胡萝卜素串联环化/环加成序列对合成几种长春花生物碱的合成能力。 将使用几种α-重氮取代的β-咔啉检查环化反应及其在长春花生物碱家族中的应用，包括塔卡明和长春卡罗定的合成。 有机与高分子化学项目通过该奖项支持埃默里大学化学系 Albert Padwa 教授的研究。 Padwa 教授的研究工作围绕使用新颖的级联序列来组装通常用于新药和农业化合物生产的复杂目标分子。提案中概述的研究也代表了本科生、研究生和博士后的理想培训，这符合 NSF 的研究和教育目标。 在这项研究期间接受培训的学生将利用这些知识为未来的药物研究做出重要贡献。