Tandem Intramolecular Michael-Anion Exchange-Olefination Methodology: New Telescoped Approaches to alpha-Methylene Lactones

串联分子内迈克尔-阴离子交换-烯化方法：α-亚甲基内酯的新望远镜方法

• 批准号: EP/E029841/1
• 负责人: Richard Taylor
• 金额: $ 45.68万
• 依托单位: University of York
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FE029841%2F1
• 关键词: Tandem; Intramolecular; Michael; Anion; Exchange

There is much current interest in the development of preparative procedures in which two or more transformations are carried out as a one-pot process. These processes offer a number of advantages to the organic chemist: in particular, they result in a reduced number of operations, giving significant time-cost benefits but also they can often allow difficult intermediate compounds to be prepared and elaborated in situ, thus preventing problems associated with their isolation and handling.The main aim of this proposal is to develop a generalised tandem intramolecular Michael-anion exchange-olefination (TIMO) sequence for the one-pot formation of alpha-methylene-lactones, thereby telescoping at 3/4 conventional processes into a one-pot procedure. The method is ideally suited to diversification/library synthesis and a solid-supported variant will be investigated leading to the possibility of an automated procedure. A range of variants will be explored tio evaluate the scope of the methodology.These TIMO methods will then be utilised to prepare a range of novel and natural alpha-methylene-lactones to validate the new chemistry. Alpha-methylene lactones are considerered to be privileged structures in terms of biological potential. Novel and natural compounds prepared in this study will therefore be made available to biological collaboratorsThe precise choice of targets will depend on the methodology studies but the starting point would be Ph. D.: paeonilactone then mayolide; PDRA: yomogin or 9-oxo-tournefolide then 5-oxo-jasoniolide then one of the more complex examples such as physalin A, ratiferolide, montahibisciolide etc.

目前人们对制备程序的发展非常感兴趣，其中两个或多个转换作为一个锅过程进行。这些工艺为有机化学家提供了许多优点：特别是，它们减少了操作次数，带来了显著的时间成本效益，而且它们通常可以原位制备和详细说明困难的中间化合物，从而防止了与它们的分离和处理相关的问题。本建议的主要目的是为α -亚甲基内酯的一锅形成开发一种通用的串联分子内迈克尔-阴离子交换烯烃（TIMO）序列，从而在3/4的常规过程中伸缩为一锅过程。该方法非常适合多样化/文库合成，并将研究固体支持的变体，从而实现自动化过程的可能性。将探讨一系列的变体，以评估该方法的范围。然后，这些TIMO方法将用于制备一系列新颖和天然的α -亚甲基内酯，以验证新的化学反应。就生物潜力而言，α -亚甲基内酯被认为是一种特殊的结构。因此，在本研究中制备的新型和天然化合物将提供给生物学合作者。靶点的精确选择将取决于方法学研究，但起点将是博士：芍药内酯，然后是蛋黄素内酯；PDRA：肌球蛋白或9-氧-萘醌内酯然后是5-氧-萘醌内酯然后是一个更复杂的例子，如physalin A， atiferolide， montahibisolide等。