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.

手性化合物以一对不可叠加的镜像(称为对映体)的形式存在，是所有生命的基石。生物体是由手性分子组成的，因此对它们相互作用的化合物的手性很敏感。因此，手性化合物被广泛应用于医药、农用化学品、香料、调味品、化妆品和精细化学品的制造。根据全球行业研究报告，2020年全球手性化学品市场价值539.3亿美元，预计到2027年底将达到1013.5亿美元。众所周知，一种化合物的不同对映体可以具有非常不同的生物活性。工业生产的许多手性化合物都需要具有对映体纯度(只有两种对映体中的一种)，因为监管机构已经认识到，当化合物的每个对映体与包括人体在内的生物系统相互作用时，可能会有不同的效果。开发稳健可靠的工艺来生产单一的化合物对映体以满足对映体手性化学品的需求是一个持续而紧迫的挑战。不对称有机催化已经成为一种强大的合成方法，它提供了一系列以前无法实现的对映选择性转化，从而产生了一系列不同的富含对映体的手性化合物。不对称有机催化利用主要来源于氨基酸的手性有机分子来激活另一个分子，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它被全球公认为一种关键的合成方法，并将2021年诺贝尔奖授予该领域的创始人。戴维斯小组正致力于有机催化的前沿，以开发新的催化剂和反应，以扩大可以进行的对映选择性反应的类型，并增加用这种催化方法可以产生的手性分子的数量。我们的重点是解决该领域的长期问题，包括开发促进光化学反应的催化剂，以及在远离催化剂的地方建立新的键。然后，我们将把这些方法应用于合成具有生物意义的化合物，展示这些催化方法在将廉价的非手性起始物质转化为高价值的、工业上相关的手性化合物方面的力量。这项工作将产生有助于解决手性化学工业当前需求的催化方法，并将产生经过独特培训的研究人员，以应对这一快速增长的经济领域面临的未来挑战。