Manufacture of Active Pharmaceutical Ingredients using Transition Metal Catalysts for Selective Functionalization of C-H Bonds

活性药物成分（api）是药物中的药用活性化合物，其生产是影响新药成本和可得性的关键领域之一。通过维多利亚大学和葛兰素史克公司的合作，我们建议开发新的、更有效的方法来合成和制造原料药。我们的目标是通过创造一种新型化学催化剂，将前体分子中普遍存在的碳氢键转变为更复杂的分子结构。这些催化剂将被专门设计为激活和破坏所需的碳氢键，然后将活化的分子传递给第二种催化剂进行细化。这种双催化剂方法将使合成的两个部分独立优化：破坏碳氢键和形成新的碳碳键。为了实现这一目标，我们将使用高通量实验来快速评估催化剂候选物，并以多元方式绘制化学反应性空间。这不仅将加速活性催化剂的发现，而且还将通过化学过程的理解为更大规模的实施提供途径。通过针对葛兰素史克公司正在开发的几个api，而不是简单的模型系统，我们也将确保我们的新催化剂适用于复杂分子的合成。最终，这项研究旨在简化新药的生产过程，减少生产过程中产生的化学废物的数量，并降低正在开发的新药的成本。

The manufacture of Active Pharmaceutical Ingredients (APIs), the medicinally-active compounds in pharmaceuticals, is one of the key areas that can affect the cost and availability of new medicines. Through a collaboration between the University of Victoria and GlaxoSmithKline, we propose to develop new, more efficient methods to synthesize and manufacture APIs. We aim to turn ubiquitous carbon-hydrogen bonds in precursor molecules into more complex molecular structures by creating a new class of chemical catalyst. These catalysts will be designed specifically to activate and break the required carbon-hydrogen bond, and then deliver the activated molecule to a second catalyst for elaboration. This dual catalyst approach will enable independent optimization of both halves of the synthesis: breaking the carbon-hydrogen bond and forming a new carbon-carbon bond.To realize this goal, we will use high-throughput experimentation to rapidly evaluate catalyst candidates and map the chemical reactivity space in a multivariate manner. Not only will this accelerate discovery of active catalysts, but also provide a path toward larger-scale implementation through chemical process understanding. By targeting several in-development APIs at GlaxoSmithKline, rather than simple model systems, we will also ensure that our new catalysts are suitable for complex molecule synthesis.Ultimately, this research aims to streamline manufacturing processes for new medicines, reduce the amount of chemical waste generated during this manufacture, and drive down the cost of new medicines under development.