Making molecules faster: Discovery dramatically reduces time it takes to
build molecules

Date:
February 8, 2023
Source:
University of Michigan
Summary:
With a big assist from artificial intelligence and a heavy dose
of human touch, a lab made a discovery that dramatically speeds
up the time- consuming chemical process of building molecules that
will be tomorrow's medicines, agrichemicals or materials.


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FULL STORY ==========================================================================
With a big assist from artificial intelligence and a heavy dose of human
touch, Tim Cernak's lab at the University of Michigan made a discovery
that dramatically speeds up the time-consuming chemical process of
building molecules that will be tomorrow's medicines, agrichemicals
or materials.


==========================================================================
The discovery, published in the Feb. 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 goal of the research was to identify key reactions in the synthesis
of a molecule, ultimately reducing 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 efficacious and nontoxic medicines, for instance, is tricky,"
said Cernak, assistant professor of medicinal chemistry and chemistry. "It requires a chemical synthesis strategy grounded in the chemical building
blocks you can actually buy and then stitch together using chemical
reactions." The accomplishment has powerful implications for speeding
up the development of medicines.

Cernak compared the construction of these complex molecules to playing
chess.

You need to orchestrate a series of moves to get to the end of the
game. While there's a near infinite number of possible moves, there's
a logic that can be followed.

"We developed a logic here, based in 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 curate the data, the researchers identified the steps along the pathway that were high impact, or key
steps, and the steps that were making progress toward completing the
synthesis but ultimately inefficient for the whole process.

"We hope this research can lead to better medicines," Cernak said. "So
far, we have been limited in the molecular structures we can quickly
access with chemical synthesis." Co-authors include Yingfu Lin,
senior research fellow in pharmacy; Rui (Sam) Zhang, doctoral student
in chemistry; and Di Wang, doctoral student in pharmacy.

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========================================================================== Story Source: Materials provided by University_of_Michigan. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Yingfu Lin, Rui Zhang, Di Wang, Tim Cernak. Computer-aided key step
generation in alkaloid total synthesis. Science, 2023; 379 (6631):
453 DOI: 10.1126/science.ade8459 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/02/230208155723.htm

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