Sustainable Pharmaceutical Manufacturing: Autonomous Development of Telescoped Catalytic Reactions

制药生产通常在多个地点使用批处理，需要几个能源密集型提纯和运输步骤，导致大量碳足迹。在不间断的反应网络中组合反应步骤(“伸缩”)有可能极大地提高制造过程的可持续性。特别令人感兴趣但也是重大挑战的是，不同类型的催化(化学、生物、光)在合成途径中的整合。这一跨学科的项目横跨利兹大学化学和化学工程学院，将研究用于开发重复催化反应的流动化学和机器学习方法，这将使药物合成的新的和可持续的路径设计成为可能。该项目有两个关键目标，每个目标都有其重大的学术研究挑战：为多步骤连续流动过程的自我优化开发新的程序。机器学习技术将与在线多点分析相结合，以快速探索催化步骤之间的复杂相互作用。设计新的多步反应器结构，以实现催化步骤的伸缩。将在连续流动条件下研究催化反应，并对不同类型的催化剂进行分隔，以使其能够在不同的反应条件下运行。研究领域(I)和(II)将结合起来，使不同类型的催化剂能够在合成途径内整合，并展示用于合成药学相关化合物的技术。这项工作将在工艺研究和开发研究所内进行。

Pharmaceutical manufacturing typically uses batch processing at multiple locations, requiring several energy-intensive purification and transportation steps, resulting in a large carbon footprint. Combination of reaction steps in uninterrupted reaction networks ('telescoping') has the potential to greatly improve the sustainability of manufacturing processes. Of particular interest, but also significant challenge, is the integration of different types of catalysis (chemical, biological, photo) within a synthetic pathway. This interdisciplinary project, based across the Schools of Chemistry and Chemical Engineering at the University of Leeds, will investigate flow chemistry and machine learning approaches for the development of telescoped catalytic reactions, which will enable the design of novel and sustainable pathways for pharmaceutical synthesis. This project has two key objectives, each with its own significant academic research challenge: Develop novel procedures for the self-optimisation of multi-step continuous flow processes. Machine learning techniques will be coupled with online multipoint analysis to rapidly explore complex interactions between catalytic steps. Design new multi-step reactor configurations for the telescoping of catalytic steps. Catalytic reactions will be investigated under continuous flow conditions, and different types of catalysts compartmentalised to enable operation at divergent reaction conditions. Research areas (i) and (ii) will be coupled to enable integration of different types of catalysts within a synthetic pathway, and the technology demonstrated towards the synthesis of pharmaceutically relevant compounds. This work will be conducted within the Institute of Process Research and Development.