Exploiting Neglected Reactivity to Develop New Tools for Organic Synthesis and Medicinal Chemistry

利用被忽视的反应性开发有机合成和药物化学的新工具

• 批准号: RGPIN-2017-05677
• 负责人: Orellana, Arturo
• 金额: $ 3.28万
• 依托单位: York University
• 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=748034
• 关键词: Exploiting; Neglected; Reactivity; Develop; New

Our research focuses on finding new and improved ways of making value-added organic molecules from simple chemical feedstocks. Although the new technology we develop will most directly impact the discovery and development of pharmaceuticals, the fundamental knowledge gained in the process will be broadly useful. Specifically, we aim to take poorly understood and undeveloped chemical processes and transform them into practical methods to make useful organic compounds. With this as a guiding principle we will tackle the following challenges:I Develop New Silver Catalysts for Heterocycle Synthesis. Nitrogen heterocycles are cylic structures made of carbon and at least one nitrogen atom, and are particularly important in pharmaceutical discovery, with most drugs having at least one such ring. Often, making these heterocycles can be challenging, slowing down drug development. We will use recent discoveries in my group to make new silver catalysts that will facilitate the synthesis of nitrogen heterocycles, allowing the rapid generation of small molecule libraries for biological testing, and thereby accelerating drug discovery and development.II Develop New Antibiotics. Antibiotics underpin modern medicine. Unfortunately, while antibiotic resistance continues to rise unabated, only two new classes of antibiotics have been developed in the last twenty years. We will use our previous research in highly strained organic molecules to develop new antibiotics. This will require the development of new methods to prepare innovative organic molecules that will interfere with cell-wall biosynthesis in bacteria. To test their antibiotic activity we will collaborate with experts in bacterial research, who will provide valuable data on active compounds. Using this feedback mechanism, we will design and prepare new molecules to arrive at new and desperately needed antibiotics. III Develop a New Way of Making Cycloheptanes. Cycloheptanes are seven-membered rings composed of carbon and are found in many naturally occurring compounds with very useful biological activity. Unfortunately, there are not many effective ways to prepare these rings, and therefore they are not widely used in drug discovery. We will develop a new reaction to make these rings in one step from simple building blocks, and demonstrate its utility by making new molecules approaching the complexity of those found in nature.Overall, our research stands to make valuable contributions to fundamental organic chemistry and will find application in the pharmaceutical sector, potentially leading to new intellectual property and new therapeutics. In addition, this research will be an integral part of the training of over 20 young scientists.

我们的研究重点是寻找从简单化学原料制作增值的有机分子的新的和改进的方法。尽管我们开发的新技术最直接地影响了药品的发现和开发，但在此过程中获得的基本知识将非常有用。具体而言，我们的目标是采用不理解和未开发的化学过程，并将其转化为实用的有机化合物的实用方法。作为指导原则，我们将应对以下挑战：我为杂环合成开发了新的银色催化剂。氮杂环是由碳和至少一个氮原子制成的囊结构，在药物发现中尤其重要，大多数药物至少具有这样的环。通常，制造这些异儿是可能具有挑战性的，从而减慢了药物的开发。我们将使用我小组中的最新发现来制造新的银催化剂，以促进氮杂环的合成，从而使小分子库的快速生成用于生物学测试，从而加速了药物发现和开发。II开发了新的抗生素。抗生素是现代医学的基础。不幸的是，尽管抗生素耐药性继续升高，但在过去的二十年中，仅开发了两种新的抗生素。我们将利用先前在高度应变的有机分子方面的研究来开发新的抗生素。这将需要开发新方法来制备创新的有机分子，这些有机分子会干扰细菌中细胞壁的生物合成。为了测试他们的抗生素活性，我们将与细菌研究专家合作，他们将提供有关活性化合物的有价值数据。使用这种反馈机制，我们将设计和准备新的分子，以获得新的急需的抗生素。 III开发了一种制造环旋植物的新方法。整体环形环是由碳组成的七元环，在许多天然存在的化合物中发现，具有非常有用的生物学活性。不幸的是，准备这些戒指的有效方法不多，因此它们并未被广泛用于药物发现。我们将开发出一种新的反应，以使这些环从简单的构建块从一个步骤中制成，并通过使新分子接近自然中发现的新分子来证明其实用性。术语，我们的研究将为基本有机化学做出宝贵的贡献，并将在药品领域中找到应用，并有可能引发新的知识产质和新的治疗疗法。此外，这项研究将是20多名年轻科学家培训的组成部分。