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

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的有机分子。虽然我们开发的新技术将最直接地影响药物的发现和开发，但在此过程中获得的基础知识将广泛有用。具体来说，我们的目标是采取不太了解和未开发的化学过程，并将其转化为实用的方法，使有用的有机化合物。以此为指导原则，我们将应对以下挑战：*I -开发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，并且在药物发现中特别重要，大多数药物具有至少一个这样的环。通常，制造这些杂环可能具有挑战性，减缓了药物开发。我们将利用我的团队最近的发现来制造新的银催化剂，这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库，从而加速药物发现和开发。二、开发新的抗生素。抗生素是现代医学的基础。不幸的是，尽管抗生素耐药性持续上升，但在过去的20年里，只有两类新的抗生素被开发出来。我们将利用我们以前在高应变有机分子方面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细胞壁的生物合成。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，以获得新的和迫切需要的抗生素。*III -开发制备环庚烷的新方法。环庚烷是由碳组成的七元环，存在于许多具有非常有用的生物活性的天然化合物中。不幸的是，没有太多有效的方法来制备这些环，因此它们没有广泛用于药物发现。我们将开发一种新的反应，从简单的积木一步到位地制造这些环，并通过制造接近自然界中发现的分子的复杂性的新分子来证明其实用性。总的来说，我们的研究将为基础有机化学做出宝贵的贡献，并将在制药领域找到应用，可能导致新的知识产权和新的疗法。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。

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.