Discovery dramatically reduces time it takes to build molecules — ScienceDaily

With a big helping of artificial intelligence and a heavy dose of human touch, Tim Cernak’s lab at the University of Michigan has made a discovery that dramatically speeds up the time-consuming chemical process of building molecules that will make tomorrow’s medicines, agricultural chemicals or materials be.

The discovery, published in the February 3 issue of Science, is the culmination of years of chemical synthesis and data science research by the Cernak Lab in the College of Pharmacy and Department of Chemistry.

The aim of the research was to identify key reactions in the synthesis of a molecule, to ultimately reduce the process to as few steps as possible. In the end, Cernak and his team achieved the synthesis of a complex alkaloid found in nature in just three steps. Previous syntheses took between seven and 26 steps.

“Making a chemical structure that has atoms in just the right place to give you, for example, effective and non-toxic medicine is difficult,” said Cernak, assistant professor of medicinal chemistry and chemistry. “It requires a chemical synthesis strategy based on the chemical building blocks that you can actually buy and then work together with chemical reactions.”

The achievement has powerful implications for speeding up drug development.

Cernak compared the construction of these complex molecules to playing chess. You have to orchestrate a series of moves to get to the end of the game. Although there are an almost infinite number of possible moves, there is a logic that can be followed.

“We developed a logic here, based on graph theory, to get to the end as quickly as possible,” he said.

Cernak and colleagues used SYNTHIA Retrosynthesis Software, which provides scientists with a database of pathways, or steps, and formulas for millions of molecular structures. This gave the team an enormous amount of computational synthesis data to play with.

Using an algorithm they developed to compile the data, the researchers identified the steps along the way that were high impact or key steps, and the steps that made progress toward completing the synthesis, but ultimately ineffective for the entire process.

“We hope this research can lead to better medicine,” Cernak said. “Until now, we have been limited in the molecular structures that we can quickly access with chemical synthesis.”

Co-authors include Yingfu Lin, senior research associate in pharmacy; Rui (Sam) Zhang, doctoral student in chemistry; and Di Wang, doctoral student in pharmacy.