Journal Article

Digitization of multistep organic synthesis in reactionware for on-demand pharmaceuticals

Cronin, Leroy, Zalesskiy, Sergey S., Mathieson, Jennifer S., Francoia, Jean-Patrick, Sigerson, Ralph C., Kitson, Philip J., Marie, Guillaume

2018

Overview

The infrastructure for chemical synthesis typically lies at either end of a spectrum: small-scale studies in ad hoc assemblies of glassware or large-scale production in capital-intensive custom reactors. Kitson et al. report a hybrid protocol that customizes a blueprint for synthesis of a target compound in a series of interconnected plastic modules, which can be assembled en masse by 3D printing (see the Perspective by Hornung). The approach, demonstrated for the commercial muscle relaxant baclofen, establishes a systematic workflow that is potentially amenable to automation: All that is necessary for synthesis and purification is the introduction of stock solutions and variation of temperature or pressure. Science , this issue p. 314 ; see also p. 273 A blueprint for chemical synthesis in plasticware offers an alternative to capital-intensive reactors for low-volume targets. Chemical manufacturing is often done at large facilities that require a sizable capital investment and then produce key compounds for a finite period. We present an approach to the manufacturing of fine chemicals and pharmaceuticals in a self-contained plastic reactionware device. The device was designed and constructed by using a chemical to computer-automated design (ChemCAD) approach that enables the translation of traditional bench-scale synthesis into a platform-independent digital code. This in turn guides production of a three-dimensional printed device that encloses the entire synthetic route internally via simple operations. We demonstrate the approach for the γ-aminobutyric acid receptor agonist, (±)-baclofen, establishing a concept that paves the way for the local manufacture of drugs outside of specialist facilities.

• Publisher: The American Association for the Advancement of Science
• Subject: Automation / Baclofen / Baclofen - chemical synthesis / Chemical synthesis / Chemistry / Chemistry Techniques, Synthetic - instrumentation / Chemistry Techniques, Synthetic - methods / Digitization / Fine chemicals / GABA-B Receptor Agonists - chemical synthesis / Glassware / Investment / Manufacturing / Muscle relaxants / Muscles / Pharmaceutical Preparations - chemical synthesis / Pharmaceuticals / Plastics / Printing, Three-Dimensional / Purification / Three dimensional printing / Workflow / γ-Aminobutyric acid