Development of selective enzyme catalysed phenol couplings

选择性酶催化苯酚偶联的发展

• 批准号: 2856080
• 金额: --
• 依托单位: University of Huddersfield
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2856080
• 关键词: Development; selective; enzyme; catalysed; phenol

"The purpose of this project is to develop enzyme catalysed inter- and intramolecular couplings of phenols to access natural product-like scaffolds for natural product synthesis and drug discovery. The project will involve the generation of novel enzymes and the evaluation of their efficacy in couplings of phenols. In particular, issues of regioselectivity and enantioselectivity in the couplings will be a major focus of this work. Phenol coupling reactions are one of the main processes used by enzymes to prepare secondary metabolites (i.e. natural products) and biopolymers such as lignin and melanin. Chemical space mapping studies have shown that natural products and drugs occupy similar chemical space, therefore developing synthetic methods to access novel natural product-like compounds is of critical importance to the future of drug discovery.Synthetic chemists have made many advances in the field of oxidative phenol coupling reactions and a diverse assortment of chiral ligands and natural products have been prepared. Unfortunately, these efforts mostly rely on the use of high loadings of expensive transition metal catalysts, diamond electrodes, or stoichiometric oxidants that are not atom economical. Crucially, many phenol coupling patterns remain inaccessible, and couplings of mono-substituted phenols are particularly difficult.Directed evolution of enzymes is a Nobel prize winning technique that allows for the rapid generation of novel enzymes. In this project, we will use sequence saturation mutagenesis techniques to generate novel enzymes. These enzymes will then be evaluated in the regioselective coupling of phenols in order to develop a facile access to a range of biaryls. In particular, the generation of compounds with coupling patterns not readily accessible by chemocatalysis will be targeted."

“该项目的目的是开发苯酚的催化酶的分子间和分子内耦合，以访问天然产物样支架以进行天然产物合成和药物发现。该项目将涉及新型酶的产生，并评估其在耦合中的功效在苯酚中。黑色素的化学空间映射研究表明，天然产品和药物占据了相似的化学空间，因此开发出新型天然产物样化合物对药物发现的未来至关重要。已经制备了氧化苯酚偶联反应以及各种各样的手性配体和天然产物。不幸的是，这些努力主要依赖于高负载昂贵的过渡金属催化剂，钻石电极或化学计量氧化剂，这些氧化剂不是原子经济的。至关重要的是，许多苯酚偶联模式仍然无法访问，单溶剂酚的苯酚的耦合尤其困难。酶的指导进化是一种诺贝尔奖获奖技术，可以快速生成新型酶。在这个项目中，我们将使用序列饱和诱变技术来生成新型酶。然后，将在苯酚的区域选择性耦合中评估这些酶，以便开发出对一系列生物体的易于访问。特别是，将针对偶联模式的化合物的产生。”