Diels-Alder/Ene Reactions for the Multi-Component Synthesis of Natural Product Inspired Bioactive Chemical Libraries

尽管在过去的50年里，健康治疗取得了许多惊人的进步，但总是需要新的药物分子。有时这是为了解决尚未找到解决办法的现有健康问题，例如某些癌症，有时这是为了处理新出现的问题，例如耐药细菌（例如耐甲氧西林金黄色葡萄球菌）的增加。现代药物的发现依赖于化学家制造新分子，作为潜在的药物进行测试，然后可以优化以供患者使用。然而，目前解决这个问题的方法可能非常耗时且效率低下。这些过程的低效率也导致产生大量的化学废物，这反过来又会造成环境问题。本项目旨在通过使用一锅化学反应来解决这个问题，在这种化学反应中，几个化学反应可以在同一个反应烧瓶中发生，而不是顺序的化学转化（一个接一个）。这种有效的方法大大减少了产生的废物，同时增加了化学家一天内可以制造的不同分子的数量，从而增加了可以测试的分子的数量。快速制造许多分子并减少浪费只会有助于加快药物发现过程。具体来说，这个项目将开发新的一锅方法，以非常快的速度建立一个由不同分子组成的文库。我们的目标分子有可能成为新的抗癌或抗菌剂，因此我们也将测试这些分子作为治疗这些疾病的先导化合物。

Despite the many fantastic advances in health treatment over the past 50 years new drug molecules are always needed. Sometimes this is to combat existing health problems for which a solution is yet to be found, such as some cancers, and sometimes this is to deal with emerging problems, such as the rise of drug resistant bacteria (e.g. MRSA). Modern drug discovery relies on chemists to make new molecules for testing as potential drugs which can be then optimised to for use by a patient. However current approaches to this problem can be very time consuming and inefficient. The inefficiency of these processes also results in the creation of large quantities of chemical waste which can in turn cause environmental problems. This project aims to find a solution to this through the use of one-pot chemical reactions where, in place of sequential chemical transformations (one after the other), several can happen in the same reaction flask. This efficient approach leads to a vast reduction in the waste generated, whilst at the same time increases the number of different molecules a chemist can make in a day and thus the number of molecules which can be tested. Making many molecules, rapidly and with a reduction in waste can only help to speed up the drug discovery process.Specifically this project will develop new one-pot methods to make a library of very different molecules, very quickly. The molecules we will target have the potential to be new anticancer or new antibacterial agents, so will also test these molecules as lead compounds for treatment of these diseases.