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Allenamides and Ynamides in Organic Synthesis.

有机合成中的烯丙酰胺和炔酰胺。

基本信息

批准号：
8536311
负责人：
RICHARD P HSUNG
金额：
$ 29.17万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-03-01 至 2015-08-31
项目状态：
已结题

项目摘要

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）：丙二烯酰胺和丙二烯酰胺，杂原子取代的丙二烯和炔的亚类，已经成为高度通用的有机配体，其适用于可用于天然产物合成的各种各样的转化。在过去的十年里，丙二烯酰胺和丙二烯酰胺的化学已经成为一个新兴的领域，包括我们自己在内的世界各地的许多团体都做出了贡献。我们已经成功地鉴定了丙二烯酰胺和丙二烯酰胺作为丙二烯胺和丙二烯胺的有用等价物，其在反应性和稳定性之间具有适当的平衡。我们已经开发了它们的实用和有效的合成途径，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的官能团，否则这些反应很难（如果不是不可能的话）使用丙二烯胺和丙二烯胺来实现。该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丙二烯酰胺完成具有立体选择性方法的复杂生物碱的全合成。具体来说，我们打算在这次更新中关注三个目标，其中两个在丙二酰胺领域，一个在丙二酰胺领域：在Aim-1中，我们打算开发N-系链IMDA反应，丙二烯酰胺的异构化。在目标-2中，我们打算设计一系列从头串联反应序列，从丙二烯酰胺？异构化在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，其特征在于Bronsted酸催化的串联酮亚胺盐Pictet-Spengler环化，涉及大环双-丙酰胺。在努力重新唤起人们对一个在很大程度上被忽视的研究领域的兴趣之后，我们有了巨大的动力，并准备不仅继续用这些新目标来证明手性丙二烯酰胺和丙二烯酰胺作为新型官能团的合成效用，而且更重要的是，将其化学带到下一个可见度水平。公共卫生关系：本更新旨在探索涉及丙二烯酰胺化学的新方法，并利用丙二烯酰胺的立体选择性方法完成复杂生物碱的全合成。在过去的十年里，丙二烯酰胺和丙二烯酰胺的化学已经成为一个新兴的领域，包括我们自己在内的世界各地的许多团体都做出了贡献。在努力重新唤起人们对一个在很大程度上被忽视的研究领域的兴趣之后，我们有着巨大的动力，并准备在这一更新中，不仅要继续证明手性丙二酰胺和丙二酰胺作为新型官能团的合成效用，而且更重要的是，要将其化学带到下一个可见度水平。