Diversity Oriented Synthesis of New Antibacterials

该奖学金和研究补助金将支持的研究的共同主题涉及开发新方法和技术，以发现生物活性小分子，如抗生素和其他药物。我们将集中讨论新方法的两个特定方面：1.多样性导向的合成，和2.三维小分子芯片技术。多样性导向合成是有机合成中的一个新概念，其目的是有效地合成结构多样的小分子集合。我们将进行以多样性为导向的合成，以获得迄今为止具有最高结构多样性的产品。由于“结构多样性”有点主观，我们还将开发软件来分析小分子的集合。我们制造的化合物将被测试其杀死“坏”细菌的能力。3-D小分子微阵列是玻璃显微镜载玻片（25 x 75 mm），其上表面上具有数千个单独的聚合物点，每个点都含有小分子。由于每个单独的斑点都有不同的化合物附着在上面，它们可以用来同时测试所有的小分子。这是一种高效的方法，可以在如此小的规模上同时测试如此多的化合物。我们将在这一领域开拓新的方法，以克服现有的问题，如信噪比和表面效应。该奖学金还将允许完成我们正在研究的其他合成方法和潜在的新抗生素的合成，如脂质A类似物和群体感应调节剂的合成。

The common theme of the research that this fellowship and research grant will support concerns the development of new approaches and techniques to discover biologically active small molecules, such as antibiotics and other drugs. There are two particular aspects of the new approaches that we will concentrate upon: 1. diversity-oriented synthesis, and 2. 3-D small molecule microarraying technology. Diversity-oriented synthesis is a new concept in organic synthesis, where the aim is to synthesise collections of structurally-diverse small molecules efficiently. We will perform a diversity-oriented synthesis to give products with the highest range of structural diversity to date. As 'structural diversity' is somewhat subjective, we will also develop software to analyse collections of small molecules. The compounds that we make will be tested for their ability to kill 'bad' bacteria. 3-D Small molecule microarrays are glass microscope slides (25 x 75 mm) that have thousands of separate polymer spots on the top surface, which contain small molecules at each spot. As each individual spot has a different compound attached to it, they can be used to test all of the small molecules at the same time. This is a highly efficient way of testing so many compounds at once on such a small scale. We will pioneer new methodology in this area to overcome existing problems such as signal-to-noise and surface effects.The fellowship will also allow the completion of other approaches we are researching in synthetic methodology and synthesis of potential new antibiotics, such as the synthesis of lipid A analogues and quorum sensing modulators.