Learning from natures's lessons: development of bioinspired catalysts for selective oxidative halogenations and their application for the creation of potent biomedical agents

汲取大自然的教训：开发用于选择性氧化卤化的仿生催化剂及其在创建有效生物医学制剂中的应用

• 批准号: 232194327
• 负责人: Professorin Dr. Tanja Gulder
• 金额: --
• 依托单位: Institut für Organische Chemie
• 依托单位国家: 德国
• 项目类别: Independent Junior Research Groups
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/232194327?language=en
• 关键词: Learning; natures; lessons; development; bioinspired

Although the halogenation of organic molecules is one of the most widespread techniques for the functionalization of substrates, efficient catalytic methods for the selective construction of carbonhalogen bonds are rare. Our research program therefore addresses the problem of catalytic halogenations by developing mild, generally applicable, and selective catalytic methods for the directed oxidative formation of carbon-halogen bonds. These goals will be achieved by using Nature as inspiration in order to imitate its concepts of highly chemo-, regio-, and stereoselective halogenation reactions. Halogenases will be mimicked by generating a chiral environment based on small‐molecule peptides around a metal ion, thus emulating the structure of the catalytically active center of the enzymes. By using these transition metal complexes as catalysts, it will become possible to accomplish not only the selective formation of aromatic and aliphatic carbon-halogen bonds, but also to perform stereo‐ and regioselective halocyclization reactions. With these catalysts, novel compound classes with unique structures and potent biological activities can be readily accessed, pushing the boundaries of chemical space for the evaluation of new scaffolds and structural elements. Our newly developed technology will thus contribute to the creation of new pathways for the synthesis of tracers for non-invasive diagnostic methods and to the discovery and exploration of novel antibiotic lead compounds.

尽管有机分子的卤化是底物功能化最广泛的技术之一，但用于选择性构建碳卤键的有效催化方法很少。因此，我们的研究计划通过开发温和的、普遍适用的和选择性的催化方法来解决催化卤化问题，以直接氧化形成碳-卤键。这些目标将通过以自然为灵感来模仿其高度化学、区域和立体选择性卤化反应的概念来实现。通过在金属离子周围产生基于小分子多肽的手性环境来模拟卤代酶，从而模拟酶的催化活性中心的结构。通过使用这些过渡金属络合物作为催化剂，不仅可以实现芳香族和脂肪族碳卤键的选择性形成，而且可以进行立体选择性和区域选择性的卤化反应。有了这些催化剂，具有独特结构和强大生物活性的新型化合物类就可以很容易地获得，从而突破了化学空间的界限，用于评估新的支架和结构元素。因此，我们新开发的技术将有助于为非侵入性诊断方法合成示踪剂创造新的途径，并有助于发现和探索新的抗生素先导化合物。