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: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=661239
• 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.

我们的研究重点是从简单的化学原料中寻找新的和改进的方法来制造增值的有机分子。尽管我们开发的新技术将最直接地影响药物的发现和开发，但在这一过程中获得的基础知识将具有广泛的用途。具体来说，我们的目标是采取知之甚少和未开发的化学过程，并将其转化为制造有用有机化合物的实用方法。以此为指导原则，我们将解决以下挑战：***I -开发新的杂环合成银催化剂。氮杂环是由碳原子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，制造这些杂环化合物是具有挑战性的，会减慢药物的开发速度。我们将利用我的小组最近的发现来制造新的银催化剂，这将促进氮杂环的合成，允许快速生成用于生物测试的小分子文库，从而加速药物的发现和开发。***II -开发新的抗生素。抗生素是现代医学的基础。不幸的是，虽然抗生素耐药性继续有增无减，但在过去二十年中只开发了两类新的抗生素。我们将利用我们之前在高张力有机分子上的研究来开发新的抗生素。这将需要开发新的方法来制备能够干扰细菌细胞壁生物合成的创新有机分子。为了测试它们的抗生素活性，我们将与细菌研究专家合作，他们将提供有关活性化合物的宝贵数据。利用这种反馈机制，我们将设计和制备新的分子，以达到新的和迫切需要的抗生素。***III -开发一种合成环庚烷的新方法。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。不幸的是，没有很多有效的方法来制备这些环，因此它们没有广泛应用于药物发现。我们将开发一种新的反应，从简单的构建块一步制造这些环，并通过制造接近自然界中发现的复杂性的新分子来证明它的实用性。***总的来说，我们的研究将为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，可能导致新的知识产权和新的治疗方法。此外，这项研究将成为培训20多名青年科学家的一个组成部分。