New Catalytic Enantioselective Desymmetrisation Reactions

手性磷(V)化合物在农化和制药工业中非常重要，因为许多成功的药物，如Remdesivir和Sofosbuvir，都是基于手性磷(V)基序。然而，迄今为止，只有少数报道的催化对映选择性方法可以用于制备高对映选择性和高纯度的新化合物。这些方法只允许获得有限数量的这类化合物的特定类别。因此，一种新方法将解锁这一相对未开发的化学空间，这将是非常有价值的。在这个项目中，我们将研究新的双功能手性催化剂，通过一种新的反对称方法有效地产生具有高对映选择性的立体性磷(V)。考虑到在构建这些物种的骨架时可能实现的排列，一种通用的、高度对映选择性的催化方法有望出现，这种方法将提供对多种化合物类别的选择性访问。这些新方法的发展，并证明它们在高生物学和医学意义分子合成中的应用将是这项工作的主要组成部分。该项目由阿斯利康共同资助，属于EPSRC合成有机化学/催化研究领域。

Chiral phosphorous (V) compounds are of high importance in the agrochemical and pharmaceutical industries as many successful drugs such as Remdesivir and Sofosbuvir are based on chiral phosphorous (V) motifs. However, to date, there are only a few reported catalytic enantioselective methods which could be used to create new such compounds with high enantioselectivity and high purity. These methods allow access to only a limited number of specific classes of such compounds. Therefore, a new method that will unlock this relatively untapped chemical space will be highly valuable.During this project we will investigate new bifunctional chiral catalysts to efficiently create stereogenic phosphorus (V) species with high enantioselectivities through a novel desymmetrisation approach. Given the possible permutations that could be achieved when building the backbone of these species, a general and highly enantioselective catalytic method that will provide selective access to multiple compound classes, will hopefully arise. The development of these new methodologies, and demonstrating their application to synthesis of molecules of high biological and medicinal significance will be a major component of this work.This project which is co-funded be AstraZeneca falls within the EPSRC Synthetic Organic Chemistry/Catalysis research area.