Ongoing research: fluorous asymmetric synthesis and new antibacterial agents

正在进行的研究：氟不对称合成和新型抗菌剂

• 批准号: 155310-2006
• 负责人: Hultin, Philip
• 金额: $ 3.21万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2007
• 资助国家: 加拿大
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=363760
• 关键词: Ongoing; research; fluorous; asymmetric; synthesis

Our ongoing research program is focused on pharmaceutical chemistry.  We are working on two projects in this general area: 1) Methods for pharmaceutical discovery synthesis - Fluorous Supported Asymmetric Synthesis.  Biologically active molecules are generally complex, often as a result of their detailed 3-dimensional geometries.  When seeking to make new drug compounds, control over this 3-dimensional aspect of structure ("stereochemistry") is important.  Drug discovery programs in pharmaceutical companies are increasingly employing automated high throughput methods, where dozens or hundreds of related molecules are synthesized in parallel.  The problem is that many of the methods available for synthesizing molecules with control over stereochemistry are not amenable to this automated environment.  We have devised tools to address this problem and this proposal describes our plans for developing and demonstrating these tools further. 2) New approaches to antibiotics - Carbohydrate-based Anti-Tuberculosis Compounds.  TB has re-emerged as a global health threat, and the complacency that followed the first successful anti-TB drugs in the post-WWII years has only recently been replaced by awareness that the bacterium has been developing multi-drug resistance and our standard treatments may not continue to be effective much longer.  There is a need for fundamentally new approaches to anti-TB drugs.  We have targeted the biosynthesis of a portion of the cell wall in Mycobacterium tuberculosis.  Previous work revealed three modestly active inhibitors of this biosynthetic pathway in laboratory tests, but much more needs to be learned if these leads are to be developed into really effective drug candidates suitable for testing in animals, let alone humans.  This proposal describes the next step in this process of exploration.

我们正在进行的研究计划集中在药物化学。我们正在这个一般领域的两个项目：1）药物发现合成的方法-氟支撑的不对称合成。生物活性分子通常是复杂的，通常是由于其详细的三维几何形状。当寻求制造新的药物化合物时，对三维结构的控制制药公司的药物发现计划越来越多地采用自动化高通量方法，其中数十个或数百个相关分子被平行合成。问题是，许多可用于合成具有立体化学控制的分子的方法不适合这种自动化环境。我们已经设计出了解决这一问题的工具，本提案描述了我们进一步开发和演示这些工具的计划。2)抗生素的新方法-基于碳水化合物的抗结核化合物结核病已重新成为全球健康威胁，二战后第一批成功的抗结核药物问世后的自满情绪，直到最近才被人们的认识所取代，即这种细菌已经发展成多种--耐药性和我们的标准治疗可能不会持续有效太久。需要从根本上新的方法来抗耐药性，结核病药物。我们的目标是结核分枝杆菌细胞壁的一部分的生物合成。以前的工作在实验室测试中揭示了这种生物合成途径的三种适度活性抑制剂，但如果这些先导物要发展成为真正有效的适合动物测试的候选药物，更不用说人类了。这个提议描述了这个探索过程的下一步。