Investigating the formation of beta-lactams via asymmetric photochemical Staudinger reactions

通过不对称光化学施陶丁格反应研究 β-内酰胺的形成

• 批准号: 2112563
• 金额: --
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2112563
• 关键词: Investigating; formation; beta; lactams; via

Modern photoredox catalysis aims to achieve chemical transformations which were hitherto impossible using milder reaction conditions and producing less waste than traditional synthetic chemistry. It does this by using visible light (usually blue), along with a small amount of catalyst (usually containing a transition metal), to perform reactions which may have traditionally necessitated the use of large amounts of chemical reagents, and which may have produced large amounts of waste and unwanted byproducts. The impact of this shift to cleaner methods of synthesis is clear - large scale production of necessary chemicals (pharmaceuticals, agrichemicals, etc.) will have a much lower impact on the environment, a key concern in today's environment.This project specifically aims to develop a new method of synthesising beta-lactams. Beta-lactams are commonly found in drug molecules and a whole class of antibiotics including penicillin derivatives (penams) contains this type of structure. These types of structure are usually functionalised (they contain some other types of structure chemically bonded to them) and this gives rise to chirality within the molecule. Most reactions cannot discriminate between forming one form (enantiomer) of a product or another. This is a key issue when only one enantiomer is desired as separation of enantiomers is costly and yields are artificially limited. With this project we wish to develop a method which can discriminate between different enantiomers and produce only the desired one, thereby maximising efficiency and minimising waste. Coupling this with efficient photocatalysis improves the reaction even more and small amounts of catalyst can be used which further minimises waste.While asymmetric photocatalysis is precedented in the literature, many of these make use of two different types of catalyst, increasing the overall amount of catalyst which needs to be used. A number of examples chiral photocatalysts which do not require the use of co-catalysts exist, but these have been used for different purposes and not for chemical structures which are directly relevant to medicinal chemistry and pharmaceuticals. The project will therefore attempt to build on the work done by others in the field on developing chiral photocatalysts and aim to apply it to reactions and reactivity which are directly relevant to challenges faced in modern chemistry.This project falls within the EPSRC Synthetic Organic Chemistry research area.

现代光催化技术的目标是利用较温和的反应条件实现迄今不可能实现的化学转化，并且比传统的合成化学产生更少的废物。它通过使用可见光(通常是蓝色)和少量催化剂(通常含有过渡金属)来执行反应，这些反应传统上可能需要使用大量的化学试剂，并且可能产生大量废物和不想要的副产品。这种转向更清洁的合成方法的影响是显而易见的--大规模生产必要的化学品(药品、农用化学品等)。对环境的影响要小得多，这是当今环境中的一个关键问题。该项目专门旨在开发一种合成β-内酰胺类药物的新方法。β-内酰胺类药物通常存在于药物分子中，包括青霉素衍生物(青霉素)在内的一整类抗生素都含有这种结构。这些类型的结构通常是官能化的(它们包含一些其他类型的结构，它们与它们化学结合)，这导致了分子中的手性。大多数反应不能区分产物的一种形式(对映体)或另一种形式。当只需要一种对映体时，这是一个关键问题，因为分离对映体的成本很高，而且产量受到人为限制。通过这个项目，我们希望开发一种方法，可以区分不同的对映体，并只生产所需的一种，从而最大限度地提高效率和减少浪费。将其与高效的光催化相结合，可以进一步改进反应，并且可以使用少量的催化剂，从而进一步减少浪费。尽管不对称光催化在文献中是先例，但其中许多使用了两种不同类型的催化剂，从而增加了需要使用的催化剂的总量。手性光催化剂存在许多不需要使用共催化剂的例子，但这些催化剂已被用于不同的目的，而不是用于与药物化学和药物直接相关的化学结构。因此，该项目将尝试在开发手性光催化剂领域的其他人所做工作的基础上，将其应用于与现代化学所面临的挑战直接相关的反应和反应性。该项目属于EPSRC合成有机化学研究领域。