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

利用镍交叉偶联催化进行药物相关有机分子的实际合成和功能化

• 批准号: 561675-2021
• 负责人: Stradiotto, MarkMJ
• 金额: $ 2.33万
• 依托单位: Dalhousie University
• 依托单位国家: 加拿大
• 项目类别: Alliance Grants
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=747679
• 关键词: Exploiting; Nickel; Cross; coupling; Catalysis

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.

在快节奏的药物发现和开发过程中，合成化学家需要有效的方法在温和、“用户友好”的条件下制备含有碳、氢和多种“杂原子”（例如氮、氧、硫、氟和其他元素）的复杂有机分子。一种方法涉及使用金属催化剂，该催化剂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”，从而允许以更简化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，解决工业合作伙伴（Paraza Pharma Inc.，蒙特利尔，QC）在专有 API 中杂原子密集化合物的靶向合成和/或修饰方面面临的特定未满足的合成化学挑战。特别是，工业合作伙伴需要开发利用廉价且丰富的反应伙伴（例如杂芳基氯）以及地球丰富的催化剂（而不是常用的贵金属催化剂）的方法。一旦开发完成，Paraza Pharma Inc. 的科学家就可以直接利用这些合成方案进行专有 API 合成和功能化。该项目的成功将大大加速工业合作伙伴的药物开发计划，从而更快地识别新疗法，造福所有加拿大人。