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重叠的镜像（称为对映体）形式存在，是所有生命的基石。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。因此，手性化合物广泛应用于医药、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为 539.3 亿美元，预计到 2027 年底将达到 1013.5 亿美元。众所周知，化合物的不同对映体可以具有截然不同的生物活性。工业生产的许多手性化合物需要纯对映体形式（仅两种对映体之一），因为监管机构已经认识到，化合物的每种对映体在与包括人体在内的生物系统相互作用时会产生不同的影响。开发稳健可靠的工艺来生产化合物的单一对映体以满足对对映纯手性化学品的需求是一个持续而紧迫的挑战。不对称有机催化已成为一种强大的合成方法，可以实现各种以前无法实现的对映选择性转化，从而产生多种对映体富集的手性化合物。不对称有机催化采用主要源自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方式促进新键的形成。这项工作的影响使其作为一种关键的合成方法获得了全球认可，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最前沿，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，并增加可以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安装新键。然后，我们将应用这些方法来合成具有生物学意义的化合物，展示这些催化方法在将廉价的非手性起始材料转化为高价值、工业相关的对映体富集的手性化合物方面的优势。这项工作将产生催化方法，有助于解决手性化学工业当前的需求，并将培养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。