Mechanistic Studies and Method Development in Asymmetric Organocatalysis

不对称有机催化的机理研究和方法开发

• 批准号: RGPIN-2022-04499
• 负责人: Davis, Rebecca
• 金额: $ 2.11万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 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=747841
• 关键词: Mechanistic; Studies; Method; Development; Asymmetric

Chiral compounds, which exist as a pair of non-superimposable mirror images (called enantiomers), are the building blocks of all life. Living organisms are comprised of chiral molecules and are therefore sensitive to the chirality of the compounds with which they interact. As a result, chiral compounds are widely used in the manufacturing of pharmaceuticals, agrochemicals, fragrances, flavourings, cosmetics and fine chemicals. The global Chiral Chemicals market was valued at $53,930 million USD in 2020 and is expected to reach $101,350 million USD by the end of 2027, according to the Global Industry Research Report. It is well established that the different enantiomers of a compound can have vastly different biological activities. Many of the chiral compounds produced industrially are required in an enantiomerically pure form (only one of the two enantiomers), as regulatory agencies have recognized that each enantiomer of a compound can have different effects when interacting with biological systems, including the human body. It is an ongoing and pressing challenge to develop robust and reliable processes that produce a single enantiomer of a compound to satisfy the demand for enantiopure chiral chemicals. Asymmetric organocatalysis has emerged as a powerful synthetic methodology that has provided access to a variety of previously unachievable enantioselective transformations, resulting in a diverse array of enantioenriched chiral compounds. Asymmetric organocatalysis employs chiral organic molecules, largely derived from amino acids, to activate another molecule and promote the formation of new bonds in a stereoselective manner. The impact of this work has led to its global recognition as a key synthetic methodology and the awarding of the 2021 Nobel Prize to the founders of the field. The Davis group is working at the forefronts of organocatalysis to develop new catalysts and reactions that will expand the types of enantioselective reactions that can be performed and increase the number of chiral molecules that can be created with this catalytic method. We are focused on addressing standing issues in the field including the development of catalysts that promote photochemical reactions and the installation of new bonds further from the catalyst. We will then apply these methods in the synthesis of biologically significant compounds, demonstrating the strength of these catalytic methods in converting cheap achiral starting materials into high value, industrially relevant enantioenriched chiral compounds. This work will generate catalytic methods that will aid in addressing the current needs of the chiral chemical industry and will produce researchers that are uniquely trained to address the future challenges facing this rapidly growing area of the economy.

手性化合物是一对非耐用的镜像图像（称为对映异构体），是所有生命的基础。活生物体由手性分子组成，因此对与其相互作用的化合物的手性敏感。结果，手性化合物被广泛用于制造药品，农业化学，香料，调味剂，化妆品和精细化学物质。根据全球行业研究报告，全球手性化学品市场的价值为53,9.3亿美元，预计到2027年底，预计将达到1.013亿美元。众所周知，化合物的不同对映异构体可以具有截然不同的生物学活动。工业产生的许多手性化合物都是在映体纯形形式（只有两个对映异构体中的一种），因为调节机构已经认识到，化合物的每个对映异构体在与包括人体在内的生物系统相互作用时都会产生不同的作用。开发出强大而可靠的过程是一个持续且紧迫的挑战，可以产生化合物的单个对映异构体，以满足对映射性手性化学物质的需求。不对称的组织分析已成为一种强大的合成方法论，它提供了对各种以前无法实现的对映选择性转换的访问，从而导致了各种富含对映的手性化合物。不对称的有机刻分析采用手性有机分子（主要源自氨基酸）来激活另一个分子，并以立体选择性的方式促进新键的形成。这项工作的影响导致了其作为关键合成方法论的全球认可，并将2021年诺贝尔奖授予该领域的创始人。 戴维斯组正在在有机刻分析的最前沿开发新的催化剂和反应，这些催化剂和反应将扩大可以执行的对映选择性反应的类型，并增加可以使用这种催化方法产生的手性分子的数量。我们专注于解决该领域的常规问题，包括开发催化剂，这些催化剂促进光化学反应以及与催化剂进一步安装新键。然后，我们将在合成具有生物学意义的化合物的合成中应用这些方法，这证明了这些催化方法在将廉价的易期起始材料转化为高价值，具有工业相关的对映体的手性化合物中的强度。这项工作将产生催化方法，有助于满足手性化学工业的当前需求，并将培养出经过独特培训的研究人员，以应对这一迅速增长的经济领域面临的未来挑战。