Abstract

Chemical Assembly Systems: Layered Control for Divergent, Continuous, Multi-step Synthesis

Kerry Gilmore, Group Leader, Max Planck Institute of Colloids and Interfaces

While continuous chemical processes have attracted both academic and industrial interest, virtually all active pharmaceutical ingredients (APIs) are still produced using multiple distinct batch processes. To date, methods for the divergent, multi-step continuous production of customizable small molecules are not available. Herein will be discussed the development of a chemical assembly system, where robust flow-reaction modules are linked together such that multiple medicines can be produced with a single system. These reaction modules are high yielding transformations with no or water-soluble byproducts and can be directly linked to subsequent reactors or via an inline workup/biphasic extraction. Several examples of such modules will be discussed, in particular our efforts with singlet oxygen generation and its utilization for the ambient and low temperature oxidation of amines. The incorporation of these reaction modules into an assembly system requires planning on a systems level, and with this mindset both convergent and divergent processes are possible, as will be shown for the synthesis of ß-amino alcohols as well as anti-malarial medicines. The latter process has been coupled to a continuous purification module, allowing for >99.5% pure medicines to be obtained from multiple natural extracts.