Development of carbon monoxide surrogates for chemical synthesis

用于化学合成的一氧化碳替代物的开发

• 批准号: 561229-2020
• 负责人: Yudin, Andrei
• 金额: $ 2.48万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Alliance Grants
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=721599
• 关键词: Development; carbon; monoxide; surrogates; chemical

The main goal of this partnership is to leverage the recently discovered carboxy-MIDA-boronate (CMB) toward site-specific introduction of labelled carbon in a range of small molecule scaffolds. Our partners - Merck and Eurofins Alphora - will primarily use CMB for labelling studies of heterocycle-containing drug leads. The Yudin group recently demonstrated the synthesis of CMB, which is a bench-stable C1-building block for the synthesis of heteroatom-rich borylated heterocycles. This technology has been protected by a patent application. In partnership with Merck & Co. and Eurofins Alphora we will expand the synthetic potential of CMB. This collaboration will be focused on exploring the numerous opportunities for the elaboration of the acyl moiety via carbonylative transformations. Efforts towards achieving our goals will rely on the high-throughput experimentation (HTE) technology provided by Merck & Co. Despite the prominence of incorporating CO in cross-coupling transformations in academic research, carbonylation has found only sparse application in industrial HTE. These findings will be of tremendous value to the Ontario-based Eurofins Alphora, the other partner on this grant. Our relationship with Eurofins Alphora is particularly significant at this challenging time as we pursue employment opportunities for the PhD and MSc graduates. By continuing our collaboration with Merck and Eurofins Alphora we will allow students to develop in a professional environment at early stages in their academic studies, and to explore short-term placements in the aforementioned companies. This will lead to the increase in amount of highly qualified personnels that are eligible to enter Canada's workforce upon graduation, thereby benefiting the overall growth of the Canadian pharmaceutical technology sector.

该合作伙伴关系的主要目标是利用最近发现的羧基-MIDA-硼酸酯（CMB）在一系列小分子支架中特异性引入标记碳。我们的合作伙伴默克和Eurofins Alphora将主要使用CMB进行含杂环药物先导化合物的标记研究。Yudin小组最近展示了CMB的合成，CMB是一种用于合成富含杂原子的硼基化杂环的工作台稳定的C1结构单元。这项技术已受到专利申请的保护。通过与默克公司和Eurofins Alphora的合作，我们将扩大CMB的合成潜力。这项合作将集中在探索通过羰基化转化来制备酰基部分的众多机会。努力实现我们的目标将依赖于高通量实验（HTE）技术提供的默克公司尽管突出纳入CO在交叉耦合转换的学术研究，羰基化只发现稀疏的应用在工业HTE。这些发现将对该赠款的另一个合作伙伴、总部位于安大略省的Eurofins Alphora具有巨大价值。我们与Eurofins Alphora的关系在这个充满挑战的时刻尤为重要，因为我们为博士和硕士毕业生寻求就业机会。通过继续与默克和Eurofins Alphora合作，我们将允许学生在学术研究的早期阶段在专业环境中发展，并探索在上述公司的短期实习机会。这将导致毕业后有资格进入加拿大劳动力市场的高素质人才数量的增加，从而有利于加拿大制药技术部门的整体增长。