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新的和改进的方法，从简单的化学原料中制造增值有机分子。尽管我们开发的新技术将最直接地影响药物的发现和发展，但在这一过程中获得的基本知识将广泛有用。具体地说，我们的目标是将鲜为人知和未开发的化学过程转化为实用的方法来制造有用的有机化合物。以此为指导原则，我们将解决以下挑战：我开发了用于杂环合成的新型银催化剂。氮杂环是由碳和至少一个氮原子组成的环状结构，在药物发现中特别重要，大多数药物至少有一个这样的环。通常情况下，制造这些杂环可能是具有挑战性的，从而减缓药物开发。我们将利用我所在团队的最新发现来制造新的银催化剂，这种催化剂将促进氮杂环的合成，从而快速生成用于生物测试的小分子文库，从而加快药物的发现和开发。抗生素是现代医学的基础。不幸的是，尽管抗生素耐药性有增无减，但在过去的20年里，只开发了两类新的抗生素。我们将利用我们之前对高度应变有机分子的研究来开发新的抗生素。这将需要开发新的方法来制备创新的有机分子，这些分子将干扰细菌的细胞壁生物合成。为了测试它们的抗生素活性，我们将与细菌研究专家合作，他们将提供关于活性化合物的有价值的数据。利用这种反馈机制，我们将设计和准备新的分子，以达到新的和迫切需要的抗生素。开发一种制造环庚烷的新方法。环庚烷是由碳组成的七元环，存在于许多天然化合物中，具有非常有用的生物活性。遗憾的是，目前还没有很多有效的方法来制备这些环，因此它们在药物开发中的应用并不广泛。我们将开发一种新的反应，从简单的积木一步就能制造出这些环，并通过制造接近自然界中发现的那些复杂程度的新分子来展示其有效性。总体而言，我们的研究将对基础有机化学做出有价值的贡献，并将在制药领域找到应用，潜在地带来新的知识产权和新的疗法。此外，这项研究将是对20多名青年科学家进行培训的一个组成部分。