Exploiting Nickel Cross-coupling Catalysis for the Practical Synthesis and Functionalization of Pharmaceutically Relevant Organic Molecules

在快节奏的药物发现和开发过程中，合成化学家需要制备含有碳、氢和多种“杂原子”（例如，氮、氧、硫、氟和其它元素）在温和的、“用户友好的”条件下进行。一种方法涉及使用金属催化剂，其允许较小部分的目标有机分子在称为交叉偶联的过程中“夹在一起”，从而允许以更精简和更具成本效益的方式组装潜在的活性药物成分（API）。该合作研究项目将寻求利用申请人研究小组开发的可持续交叉偶联催化方面的最新专业知识，以解决工业合作伙伴（帕拉扎制药公司，Montreal，QC）关于专有API中杂原子密集化合物的靶向合成和/或修饰。特别地，工业合作伙伴需要开发利用廉价和丰富的反应伙伴（例如，杂芳基氯化物）以及富含地球的催化剂（而不是通常使用的贵金属催化剂）。一旦开发出来，这些合成方案可以直接由帕拉扎制药公司的科学家开发。专利API合成和功能化。该项目的成功将大大加快工业合作伙伴的药物开发计划，从而更快地确定新的疗法，造福所有加拿大人。

In the fast-paced drug discovery and development process, synthetic chemists require efficient methods of preparing complex organic molecules that contain carbon, hydrogen, and a diversity of 'heteroatoms' (e.g., nitrogen, oxygen, sulfur, fluorine and other elements) under mild, 'user-friendly' conditions. One method involves the use of metal catalysts that allow smaller portions of targeted organic molecules to be 'clipped together' in a process called cross-coupling, thus allowing for the assembly of potential active pharmaceutical ingredients (APIs) in a more streamlined and cost-effective manner. This collaborative research project will seek to exploit recent expertise in sustainable cross-coupling catalysis developed by the applicant's research group, in addressing specific unmet synthetic chemistry challenges faced by the industrial partner (Paraza Pharma Inc., Montreal, QC) with regard to the targeted synthesis and/or modification of heteroatom-dense compounds within proprietary APIs. In particular, the industrial partner requires the development of methodologies that make use of cheap and abundant reaction partners (e.g., heteroaryl chlorides), as well as Earth abundant catalysts (rather than precious metal catalysts that are commonly employed). Once developed, these synthetic protocols can be exploited directly by scientists at Paraza Pharma Inc. in proprietary API synthesis and functionalization. Success in this project will greatly accelerate the industrial partner's drug development program, thereby leading to more rapid identification of novel therapies to the benefit of all Canadians.