Automated Complex Molecular printer for making organic small molecules could speed drug development

A new molecule-making machine could do for chemistry what 3-D printing did for engineering: Make it fast, flexible and accessible to anyone.

Chemists at the University of Illinois, led by chemistry professor and medical doctor Martin D. Burke, built the machine to assemble complex small molecules at the click of a mouse, like a 3-D printer at the molecular level. The automated process has the potential to greatly speed up and enable new drug development and other technologies that rely on small molecules.

“We wanted to take a very complex process, chemical synthesis, and make it simple,” said Burke, a Howard Hughes Medical Institute Early Career Scientist. “Simplicity enables automation, which, in turn, can broadly enable discovery and bring the substantial power of making molecules to nonspecialists.”

Carbon-based small molecules involved in biochemistry and drug design exhibit extraordinary structural diversity. But can we come up with a general set of building blocks from which a machine could put most of them together, in assembly-line fashion? Li et al. present progress toward this goal by showcasing the range of structures available via coupling reactions of fragments bearing a specific type of boronate group. They successfully made complex polycyclic structures by stringing together a linear precursor and then coaxing it to fold back on itself. They also developed a purification method that facilitates automation of the reaction and product isolation.