Bioinspired Oxidation of Organic Molecules with Organic (Co-)Catalysts

氧化反应在天然药物合成中显示出重要的价值 产品和其他生物活性化合物，因为它们往往有助于引入 将杂原子注入这些分子中。执行氧化的大多数方法 反应依赖于不受欢迎的氧化剂，这些氧化剂产生化学计量废物，通常 限制了它们在大规模应用中的使用(例如，工艺规模的制药 综合)。相比之下，大自然广泛使用最丰富的氧化剂O2，在选择性 氧化反应。许多加氧酶和加氧酶具有氧化还原活性的有机物质 (Co)酶活性部位的催化剂，如苯二酚和酪氨酸基。在……里面 在建议的工作中，我们将开发由两类生物启发催化的反应 用于合成氧化反应的氧化还原活性(CO)催化剂：(1)苯二酚催化剂 胺类化合物的氧化脱氢和氧化偶联反应 底物，(2)用于氧化偶联反应的氮氧基(CO)催化剂，以及对映体。 醇的非对映氧化和化学选择性氧化。苯二酚催化的反应 将促进N-杂环的脱氢和氧化偶联反应，这 50%的小分子药物中含有这种物质。铜/氮氧基化学将被用于 实现多种氧化偶联反应，以生成酰胺、氨基甲酸酯和 尿素以及复杂分子中的位置选择性乙醇氧化，包括晚期- 天然产品和药品的阶段性功能化。在这两个项目中 在这些领域，经验反应发现工作将得到整体机制的补充 (CO)催化剂的催化机理和氧化还原行为的研究。

Oxidation reactions exhibit significant value in the synthesis of pharmaceuticals, natural products and other bioactive compounds, since they often facilitate the introduction of heteroatoms into these molecules. The majority of methods for performing oxidation reactions rely on undesirable oxidants that generate stoichiometric waste, which often limits their use in large-scale applications (e.g., process-scale pharmaceutical synthesis). In contrast, Nature widely uses the most abundant oxidant, O2, in selective oxidation reactions. Many oxygenases and oxidases feature redox-active organic (co)catalysts, such as quinones and tyrosyl radicals, in the active site of the enzyme. In the proposed work, we will develop reactions catalyzed by two classes of bioinspired redox-active (co)catalysts for synthetic oxidation reactions: (1) quinone catalysts for oxidative dehydrogenation and oxidative coupling reactions of amines and other substrates, (2) nitroxyl radical (co)catalysts for oxidative coupling reactions, and enantio- , diastereo-, and chemoselective oxidations of alcohols. The quinone-catalyzed reactions will facilitate dehydrogenation and oxidative coupling reactions of N-heterocycles, which are present in >50% of small-molecule drugs. The Cu/nitroxyl chemistry will be used to achieve versatile oxidative coupling reactions to generate amides, carbamates, and ureas as well as site-selective alcohol oxidation in complex molecules, including late- stage functionalization of natural products and pharmaceuticals. In both of these project areas, empirical reaction discovery efforts will be complemented by holistic mechanistic studies of the catalytic mechanisms and redox behavior of the (co)catalysts.