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."

“这个项目的目的是开发酶催化的酚的分子间和分子内偶联，以获得天然产物样支架，用于天然产物合成和药物发现。该项目将涉及新酶的产生和评价它们在酚偶联中的功效。特别是，耦合中的区域选择性和对映体选择性问题将是这项工作的主要焦点。苯酚偶联反应是酶制备次生代谢产物（即天然产物）和木质素、黑色素等生物聚合物的主要过程之一。化学空间映射研究表明，天然产物和药物占据相似的化学空间，因此开发合成方法来获取新的天然产物类化合物对未来的药物发现至关重要。合成化学家在氧化苯酚偶联反应领域取得了许多进展，制备了各种各样的手性配体和天然产物。不幸的是，这些努力大多依赖于使用大量昂贵的过渡金属催化剂、金刚石电极或化学计量氧化剂，这些都不是原子经济的。至关重要的是，许多苯酚偶联模式仍然无法获得，单取代苯酚的偶联尤其困难。酶的定向进化是一项获得诺贝尔奖的技术，它允许快速产生新的酶。在这个项目中，我们将使用序列饱和诱变技术来产生新的酶。然后，这些酶将在酚的区域选择性偶联中进行评估，以便开发一种易于获得一系列双芳基的途径。特别是，具有不易通过化学催化获得的偶联模式的化合物的生成将成为目标。”