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

尽管有机分子的卤化是用于基底官能化的最广泛的技术之一，但是用于选择性构建碳卤键的有效催化方法是罕见的。因此，我们的研究计划通过开发温和、普遍适用且选择性的催化方法来直接氧化形成碳-卤键，从而解决催化卤化问题。这些目标将通过使用大自然作为灵感来实现，以模仿其高度化学，区域和立体选择性卤化反应的概念。卤素酶将通过在金属离子周围产生基于小分子肽的手性环境来模拟，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配合物作为催化剂，不仅可以实现芳香族和脂肪族碳-卤键的选择性形成，而且可以进行立体和区域选择性卤环化反应。有了这些催化剂，可以很容易地获得具有独特结构和有效生物活性的新型化合物类别，从而推动化学空间的边界，以评估新的支架和结构元件。因此，我们新开发的技术将有助于创造用于非侵入性诊断方法的示踪剂合成的新途径，并有助于发现和探索新型抗生素先导化合物。

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.