Allenamides and Ynamides in Organic Synthesis.

有机合成中的烯丙酰胺和炔酰胺。

• 批准号: 8324684
• 负责人: RICHARD P HSUNG
• 金额: $ 30.23万
• 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/8324684
• 关键词: Acids; Alder plant; Alkaloids; Alkynes; Amination; Area; Biological Factors; Chemistry; Complex; Coupling; Cyclization; Equilibrium; Goals; Methodology; Methods; Organic Synthesis; Process; Reaction; Research; Series; Subgroup; TANDEM; United States National Institutes of Health; bone morphogenetic protein 7; cycloaddition; design; functional group; interest; novel; propadiene; public health relevance

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

描述（由申请人提供）：烯丙酰胺和炔酰胺，杂原子取代的丙二烯和炔烃的亚类，已成为高度通用的有机合成子，适用于可用于天然产物合成的多种转化。在过去的十年中，丙二烯酰胺和炔酰胺的化学已成为一个新兴领域，得到了包括我们自己在内的世界各地许多团体的贡献。我们已经成功地将丙二烯酰胺和炔酰胺鉴定为丙二烯胺和炔胺的有用等价物，它们在反应性和稳定性之间具有适当的平衡。我们开发了它们实用且有效的合成方法，并在高度立体选择性的分子间和分子内反应中实现了这些新颖的官能团，否则使用烯胺和炔胺很难甚至不可能实现这些反应。 NIH 更新的目标是探索涉及丙二烯酰胺化学的新型串联方法，并使用丙二烯酰胺和炔酰胺实现以立体选择性方法为特征的复杂生物碱的全合成。 具体来说，我们打算在这次更新中重点关注三个目标，其中两个在丙二烯酰胺领域，一个在丙二烯酰胺领域：在Aim-1中，我们打算开发与丙二烯酰胺β-异构化串联的N-束缚IMDA反应。在Aim-2中，我们打算设计一系列从丙二烯酰胺β-异构化引发的从头串联反应序列。在 Aim-3 中，我们打算追求以这些新颖的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(+)-thalbadenzine的全合成，其特点是布朗斯台德酸催化的串联烯酮亚胺Pictet-Spengler环化涉及大环双炔酰胺。 我们带头努力重振人们对一个在很大程度上被忽视的研究领域的兴趣，我们拥有巨大的动力，不仅准备继续通过这些新目标证明手性丙二烯酰胺和炔酰胺作为新型官能团的合成效用，而且更重要的是，将其化学作用提升到新的可见度水平。 公共健康相关性：本次更新旨在探索涉及丙二烯酰胺化学的新方法，并利用炔酰胺的立体选择性方法完成复杂生物碱的全合成。在过去的十年中，丙二烯酰胺和炔酰胺的化学已成为一个新兴领域，得到了包括我们自己在内的世界各地许多团体的贡献。我们带头努力重振人们对一个在很大程度上被忽视的研究领域的兴趣，我们拥有巨大的动力，并准备好进行这一更新，不仅要继续展示手性丙二烯酰胺和炔酰胺作为新型官能团的合成效用，而且更重要的是，将其化学的可见性提升到一个新的水平