Digital design and 3D printing of reactionware for on demand synthesis of high value probes

Performing chemical transformations in a standardised way is important for increasing the accessibility to high value reagents for specific purposes. Building on the use of 3D-printed reactionware, we present a new concept in the design of reactionware devices for generating such high value compounds. In this approach integrated reactor sequences are treated as modular, with each module able to effect a specific chemical transformation, rather than individual chemical processing steps. The initial workflow is mapped into a core set of modules, and different synthetic pathways can be selected by attaching different peripheral modules in a 'plug and react manner'. We utilised this system to synthesise a set of diazirine based photoaffinity probes. Starting from appropriately functionalised starting materials, a core sequence of reactors furnishes a central diazirine moiety on a variable sized molecular scaffold, with exchangeable peripheral reactors facilitating the attachment of auxiliary moieties. Yields and purities range from 29-39% and 93-97%, respectively, comparable to, or exceeding literature yields for similar compounds. The activity of photoprobes produced was validated by analysis of their interaction with the peptide hormone, human Angiotensin II. A new modular approach to 3D printed reactionware design is presented, and its effectiveness demonstrated in the synthesis of a number of structurally related, diazirine based, photoaffinity probes.

Automated summary

Performing chemical transformations in a standard way is important for accessibility to high value reagents. This study presents a new concept in reactionware design using 3D printing, allowing the generation of high value compounds. By treating integrated reactor sequences as modular, different synthetic pathways can be selected.