title: Chemical assembly systems: layered control for divergent, continuous, multistep syntheses of active pharmaceutical ingredients.
abstract: While continuous chemical processes have attracted both academic and industrial interest, virtually all active pharmaceutical ingredients (APIs) are still produced by using multiple distinct batch processes. To date, methods for the divergent multistep continuous production of customizable small molecules are not available. A chemical assembly system was developed, in which flow-reaction modules are linked together in an interchangeable fashion to give access to a wide breadth of chemical space. Control at three different levels--choice of starting material, reagent, or order of reaction modules--enables the synthesis of five APIs that represent three different structural classes (γ-amino acids, γ-lactams, β-amino acids), including the blockbuster drugs Lyrica and Gabapentin, in good overall yields (49-75%).
authors.affiliation: Department of Biomolecular Systems, Max-Planck Institute for Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam (Germany), Institute for Chemistry and Biochemistry, Freie Universität Berlin, Arnimalle 22, 14195 Berlin (Germany).
authors.forename: Diego
authors.initials: D
authors.lastname: Ghislieri
authors.forename: Kerry
authors.initials: K
authors.lastname: Gilmore
authors.forename: Peter H
authors.initials: PH
authors.lastname: Seeberger
mesh_terms: D004364:Pharmaceutical Preparations / Q000138:chemical synthesis*
chemical_list: D004364:Pharmaceutical Preparations
keywords: active pharmaceutical ingredients; chemical assembly; divergent synthesis; flow chemsitry; γ-amino acids