Cross-Coupling Reactions Leading to Chiral Heterocyclic Scaffolds for Drug Development and Manufacturing

杂环化合物是一类具有至少一个非碳原子的环状分子，由于其良好的物理和化学性质而被广泛应用于药物发现和开发。吡啶是FDA批准的药物中最广泛使用的芳族杂环，并且对制备它们及其衍生物的方法存在持续的需求。不幸的是，大多数这样做的方法采用苛刻的反应条件，因此没有广泛使用。我们设计了一种概念上的新方法，使吡啶衍生物使用非常温和的条件下，容忍广泛的官能团。这些反应还提供了直接获得具有“药物样”性质的小分子的途径，这些小分子很难通过其他方式制造。最后，我们的方法是催化剂，因此将有助于减少药物发现和开发的环境成本。因此，拟议的研究将对寻找新的治疗药物产生直接影响。

Heterocycles, cyclic molecules with at least one non-carbon atom, are widely used in drug discovery and development due to their favourable physical and chemical properties. Pyridines are the most widely used aromatic heterocycle in FDA approved drugs and there is a continued demand for methods to prepare them and their derivatives. Unfortunately, the majority of methods to do this employ harsh reaction conditions and are therefore not widely useful. We have devised a conceptually new approach to make pyridine derivatives using exceptionally mild conditions that tolerate a wide range of functional groups. These reactions also provide immediate access to small molecules that possess 'drug-like' qualities and that are hard to make by other means. Finally, our methods are catalytic and therefore will contribute to the reduction of the environmental costs of drug discovery and development. As a result, the proposed research will have a direct impact on the search for new therapeutic agents.