Application of Cascade Processes for the Synthesis of Polycyclic Ring Systems

通过这一奖项，化学合成计划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奇的级联序列来组装复杂的目标分子。将不同反应类型的转化结合在一起的合成方法极大地拓宽了合成化学中此类过程的范围。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。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。α-重氮二羰基化合物作为合成中间体很有吸引力，因为它们容易获得，相当坚固，并在环化产物中留下官能团，有助于进一步的合成转化。就更广泛的影响而言，这项工作有望广泛应用于有机合成领域。根据这笔赠款正在开发的新型级联序列在制药和农业部门生产关键目标分子方面具有潜在的应用。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和学术研究中做出重要贡献。

With this award, the Chemical Synthesis 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. Synthetic methods that combine transformations of different reaction types significantly broaden the scope of such procedures in synthetic chemistry. 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. 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. alpha-Diazo-dicarbonyl compounds are appealing as synthetic intermediates in that they are readily accessible, are reasonably robust and leave functionality in the cyclized product that is useful for further synthetic transformation. In terms of broader impacts, the work is expected to have wide application to the field of organic synthesis. The novel cascade sequences being developed under this grant have potential application for the production of key target molecules in the pharmaceutical and agricultural sectors. 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 and academic research.