Sustainable Pharmaceutical Manufacturing: Autonomous Development of Telescoped Catalytic Reactions

药品生产通常在多个地点进行批量处理，需要几个能源密集型的净化和运输步骤，导致大量的碳足迹。不间断反应网络中反应步骤的组合（“伸缩”）有可能大大提高制造过程的可持续性。特别有趣的是，在合成途径中整合不同类型的催化（化学，生物，光）也是一个重大挑战。这个跨学科项目，基于利兹大学化学和化学工程学院，将研究流动化学和机器学习方法用于伸缩催化反应的开发，这将使设计新的和可持续的药物合成途径成为可能。该项目有两个关键目标，每个目标都有自己的重大学术研究挑战：开发用于多步骤连续流过程自我优化的新程序。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复杂的相互作用。设计新的多步反应器配置，用于伸缩催化步骤。催化反应将在连续流动条件下进行研究，不同类型的催化剂将被分隔，以便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中整合，并证明该技术可以合成药学上相关的化合物。这项工作将在工艺研究与发展研究所内进行。

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.