Application of Cascade Processes for the Synthesis of Polycyclic Ring Systems

该项目将利用新的级联序列来组装复杂的目标分子。近期的目标之一是开发一种新的合成哌啶的方法，该方法使用不同的肟类与2，3-二(苯磺酰基)-1，3-二烯进行串联反应。氮杂-氧杂二环环加成物的形成涉及到酮在二烯上的共轭加成，得到瞬时的硝酮，然后再进行分子内偶极环加成反应。研究目标还要求使用相关的一系列反应来正式合成新型海洋生物碱卤代氯。2-氨基取代呋喃的分子内Diels-Alder环加成/重排反应是制备多种天然生物碱的一种非常有效的策略。作为该项目的一部分，将使用这种层叠方法研究马钱子五环骨架的制备。另一个目标将是探索串联环化/环加成序列对合成几种长春花碱的合成能力。将研究几种α-重氮取代β-卡宾的环化反应及其在长春花碱家族中的应用，包括他卡胺和长春花碱的合成。通过这一奖项，有机化学和高分子化学项目正在支持埃默里大学化学系的阿尔伯特·帕德瓦教授的研究。帕德瓦教授的研究工作围绕着使用新颖的级联序列来组装复杂的目标分子，这些分子通常用于生产新药和农业化合物。提案中概述的研究也代表了对本科生、研究生和博士后的理想培训，这与NSF的研究和教育目标是一致的。在这项研究的实施过程中接受培训的学生将利用这些知识在未来的药学研究中做出重要贡献。

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.