Allenamides and Ynamides in Organic Synthesis.

有机合成中的烯丙酰胺和炔酰胺。

• 批准号: 7985283
• 负责人: RICHARD P HSUNG
• 金额: $ 30.53万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7985283
• 关键词: Organic Synthesis

DESCRIPTION (provided by applicant): Allenamides and ynamides, subgroups of heteroatom-substituted allenes and alkynes, have become highly versatile organic synthons applicable to a diverse array of transformations that can be useful for natural product syntheses. In the last ten years, the chemistry of allenamides and ynamides has become an emerging field with contributions from many groups around the world including our own. We have succeeded in identifying allenamides and ynamides as useful equivalents of allenamines and ynamines that possess the right balance between reactivity and stability. We have developed their practical and efficient synthetic access, and implemented these novel functional groups in highly stereoselective inter- and intramolecular reactions that were otherwise difficult, if not impossible, to achieve using allenamines and ynamines. The goals of this NIH renewal are to explore novel tandem methods involving the allenamide chemistry, and to accomplish total syntheses of complex alkaloids featuring stereoselective methods using both allenamides and ynamides. Specifically, we intend to focus on three Aims in this renewal with two in the area of allenamides and one in the area of ynamides: In Aim-1, we intend to develop N-tethered IMDA reactions in tandem with ?-isomerization of allenamides. In Aim-2, we intend to design a series of de novo tandem reaction sequences initiated from allenamide ?-isomerizations. In Aim-3, we intend to pursue a total synthesis of (+)-davisine featuring one of these novel tandem reactions. In Aim-4, we intend to accomplish a total synthesis of (+)-thalbadenzine featuring a Bronsted acid catalyzed tandem keteniminium Pictet-Spengler cyclization involving a macrocyclic bis-ynamide. Having led the efforts in revitalizing interest in a research area that has been largely overlooked, we have a tremendous amount of momentum and are poised not only to continue demonstrating with these new Aims the synthetic utility of chiral allenamides and ynamides as novel functional groups, but more significantly, to take their chemistry to the next level of visibility. PUBLIC HEALTH RELEVANCE: This renewal intends to explore novel methods involving the allenamide chemistry and accomplish the total synthesis of a complex alkaloid featuring stereoselective methods using ynamides. In the last ten years, the chemistry of allenamides and ynamides has become an emerging field with contributions from many groups around the world including our own. Having led the efforts in revitalizing interest in a research area that has been largely overlooked, we have a tremendous amount of momentum and are poised in this renewal, not only to continue demonstrating the synthetic utility of chiral allenamides and ynamides as novel functional groups, but also more significantly, to take their chemistry to the next level of visibility

说明书(申请人提供)：烯丙酰胺和丙烯酰胺，杂原子取代的烯和炔的亚基，已经成为用途非常广泛的有机合成体，适用于各种转化，可用于天然产物的合成。在过去的十年里，联苯酰胺和异氰胺的化学已经成为一个新兴的领域，世界各地的许多团体都做出了贡献，包括我们自己的团体。我们已经成功地确定了联烯酰胺和联胺是联胺和联胺的有效等价物，它们在反应性和稳定性之间取得了适当的平衡。我们开发了它们实用而有效的合成途径，并将这些新的官能团应用于高度立体选择性的分子间和分子内反应，否则使用联氨酰胺和亚氨酸胺很难实现这些反应。NIH此次更新的目标是探索涉及尿囊酰胺化学的新串联方法，并完成具有立体选择性方法的复杂生物碱的全合成，该方法同时使用尿囊酰胺和尿囊素。具体地说，我们打算在这次更新中重点关注三个目标，两个在烯丙酰胺领域，一个在亚胺领域：在AIM-1中，我们打算开发N-栓系的IMDA反应与烯丙酰胺的？-异构化。在AIM-2中，我们打算设计一系列由烯丙酰胺异构化引发的从头开始的串联反应序列。在AIM-3中，我们打算进行以这些新型串联反应之一为特征的(+)-Davisine的全合成。在AIM-4中，我们打算完成一个以Bronsted酸催化的串联的酮亚胺Pictet-Spengler环化反应为特征的(+)-地中海苯并胺的全合成，该环化反应涉及大环双氰胺。在领导了重振人们对一个在很大程度上被忽视的研究领域的兴趣的努力后，我们拥有了巨大的动力，并准备继续利用这些新的目标来展示手性联胺和氰胺作为新的官能团的合成用途，更重要的是，将它们的化学带入下一个可见度水平。 与公共健康相关：此次更新旨在探索涉及尿囊酰胺化学的新方法，并完成一种具有立体选择性方法的复杂生物碱的全合成。在过去的十年里，联苯酰胺和异氰胺的化学已经成为一个新兴的领域，世界各地的许多团体都做出了贡献，包括我们自己的团体。在领导了重振人们对一个在很大程度上被忽视的研究领域的兴趣的努力之后，我们有了巨大的动力，并准备在这次更新中，不仅继续展示手性联胺和氰胺作为新的官能团的合成用途，而且更重要的是，将它们的化学带入下一个可见度水平。