Discovery and mechanistic analysis of new catalytic reactions

新催化反应的发现和机理分析

• 批准号: RGPIN-2021-03836
• 负责人: Taylor, Mark
• 金额: $ 6.85万
• 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: 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=748369
• 关键词: Discovery; mechanistic; analysis; new; catalytic

Controlling selectivity in reactions of complex molecules is a critical challenge for the chemistry field. The efficient and rapid preparation of drug candidates, new materials and tools for studying biochemical processes often hinges on the development of selective chemical transformations. Selectivity in organic synthesis is a multifaceted problem, encompassing stereoselectivity (control of the orientation of atoms in space), regioselectivity (control of the direction of bond formation), site-selectivity (positional selectivity in a molecule with several copies of the same reactive group) and chemoselectivity (reactivity of one group of atoms over another). In nature, these types of selectivity are under the control of enzyme catalysts, which accelerate one pathway so that it can outcompete other possibilities. Catalyst control of selectivity is one of the primary ways that nature constructs structurally and functionally diverse molecules from a set of simple precursors. The goal of the proposed research is to develop synthetic (laboratory) catalysts to address important problems related to the control of regioselectivity, stereoselectivity and site-selectivity in the preparation of organic compounds. Efficient methods for the synthesis or functionalization of carbohydrate (sugar) and nucleoside derivatives or analogs are a specific area of focus; these types of molecules are the building blocks for oligosaccharides and polynucleotides, two important classes of biological compounds. Their derivatives and analogs are used extensively in basic research and as prospective medicinal agents, particularly as antivirals or antibiotics. These structural classes pose particularly challenging selectivity issues; methods for their efficient laboratory synthesis are urgently needed to advance understanding of human health and disease and to enable the development of new drug candidates. Supported by our previous Discovery Grant, my group pioneered new catalytic reactions that have been widely adopted by end users in the carbohydrate chemistry and glycobiology communities to facilitate their research efforts, and have inspired further innovations by other catalysis researchers. Over the next five years, my team of diverse graduate and undergraduate students will conduct laboratory experiments to develop new catalytic processes of strategic value for the synthesis of carbohydrates, nucleosides and other complex chemical targets. By studying details of how these reactions work, they will build understanding of how to optimize and generalize them. The results will define new ways to prepare and study compounds that are urgently needed in the biochemistry, biotechnology and medicinal chemistry fields. While conducting this research, trainees will develop into well-rounded, creative and resourceful scientists while building valuable skills in modern synthetic and spectroscopic techniques, experimental design, data analysis and interpretation.

控制复杂分子反应的选择性是化学领域的一个关键挑战。有效和快速制备候选药物、新材料和研究生化过程的工具往往取决于选择性化学转化的发展。有机合成中的选择性是一个多方面的问题，包括立体选择性（控制原子在空间中的取向）、区域选择性（控制键形成的方向）、位点选择性（在具有相同反应基团的几个拷贝的分子中的位置选择性）和化学选择性（一个原子团对另一个原子团的反应性）。在本质上，这些类型的选择性是在酶催化剂的控制下，酶催化剂加速一种途径，使其能够超越其他可能性。催化剂对选择性的控制是自然界从一组简单的前体构建结构和功能多样的分子的主要方式之一。 拟议研究的目标是开发合成（实验室）催化剂，以解决与控制有机化合物制备中的区域选择性，立体选择性和位点选择性有关的重要问题。碳水化合物（糖）和核苷衍生物或类似物的合成或功能化的有效方法是一个特定的关注领域;这些类型的分子是寡糖和多核苷酸的构建模块，这两类重要的生物化合物。它们的衍生物和类似物广泛用于基础研究和作为有前景的药物，特别是作为抗病毒药或抗生素。这些结构类别提出了特别具有挑战性的选择性问题;迫切需要有效的实验室合成方法来促进对人类健康和疾病的理解，并能够开发新的候选药物。在我们之前的发现资助的支持下，我的团队开创了新的催化反应，这些反应已被碳水化合物化学和糖生物学领域的最终用户广泛采用，以促进他们的研究工作，并激发了其他催化研究人员的进一步创新。在接下来的五年里，我的研究生和本科生团队将进行实验室实验，开发具有战略价值的新催化工艺，用于合成碳水化合物，核苷和其他复杂的化学目标。通过研究这些反应如何工作的细节，他们将了解如何优化和推广它们。研究结果将确定制备和研究生物化学、生物技术和药物化学领域迫切需要的化合物的新方法。在进行这项研究的同时，学员将发展成为全面，创造性和足智多谋的科学家，同时在现代合成和光谱技术，实验设计，数据分析和解释方面建立宝贵的技能。