New Strategies for the Synthesis of Medicinally Relevant Small Molecules

合成医学相关小分子的新策略

• 批准号: RGPIN-2021-03533
• 负责人: Rousseaux, Sophie
• 金额: $ 4.66万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 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=742603
• 关键词: New; Strategies; Synthesis; Medicinally; Relevant

The desire to efficiently and safely prepare value-added organic molecules from simple building blocks remains a key driving force in the chemical industry and has shaped the field of organic synthesis in recent decades. The transformation of chemical building blocks into medicines or fine chemicals typically requires numerous synthetic steps, leading to an increase in manufacturing costs and the production of chemical waste. The reagents used in these transformations and the waste that is generated may also be toxic or corrosive, leading to additional complications for reaction set-up, waste disposal and product purification. My research program focuses on developing enabling synthetic methods to access medicinally relevant small molecules in a more efficient (e.g. less waste, fewer steps) and/or safer (e.g. non-toxic reagents/waste) manner. In particular, our recent efforts have focused on the development of new methods to prepare and functionalize cyclopropane- and nitrile-containing molecules given the importance of these substrate classes in the pharmaceutical and agrochemical industries. The research that will be proposed in this NSERC Discovery Grant application will focus on using the expertise we have gained over the last 5 years to develop new enabling technologies for synthetic organic chemists. We will maximize impact on our recent discoveries in the area of Ni-catalysis involving 1-electron chemistry to develop 1) a broad scope of reductive cyanation reactions and 2) cross-coupling reactions involving C(sp3)-O electrophiles. Furthermore, as pioneers of the use of electrophilic homoenolates, we will exploit these reagents for the synthesis of small 3- and 4-membered rings. Throughout this program, we will focus on target selection, to ensure we are preparing molecules of high interest to research end-users (e.g. industrial chemists), and mechanistic studies, to enable new catalyst/reagent design and the exploration of new chemical reactivity.

从简单的结构单元高效安全地制备增值有机分子的愿望仍然是化学工业的关键驱动力，并在近几十年来塑造了有机合成领域。将化学构件转化为药物或精细化学品通常需要许多合成步骤，导致制造成本增加和化学废物的产生。在这些转化中使用的试剂和产生的废物也可能是有毒的或腐蚀性的，导致反应设置、废物处置和产物纯化的额外复杂性。我的研究项目重点是开发能够以更有效（例如更少的浪费、更少的步骤）和/或更安全（例如无毒试剂/废物）的方式获得医学相关小分子的合成方法。特别是，我们最近的努力集中在开发新的方法来制备和官能化环丙烷和腈的分子，这些底物类在制药和农业化学工业的重要性。在NSERC发现资助申请中提出的研究将侧重于利用我们在过去5年中获得的专业知识为合成有机化学家开发新的使能技术。我们将最大限度地影响我们最近在涉及单电子化学的Ni催化领域的发现，以开发1）广泛的还原氰化反应和2）涉及C（sp3）-O亲电试剂的交叉偶联反应。此外，作为使用亲电子homoenolates的先驱，我们将利用这些试剂的小3-和4-元环的合成。在整个计划中，我们将专注于目标选择，以确保我们正在制备研究最终用户（例如工业化学家）高度感兴趣的分子，以及机理研究，以实现新的催化剂/试剂设计和新的化学反应性的探索。