Scientists Innovate "Hook and Slide" Method To Improve Drug Discovery
A new study shows how chemists can use a “hook and slide” technique to more easily create certain molecules.
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Historically, one of the primary ways organic chemists have explored and created compounds is by constructing a carbon skeleton and making modifications to its structure.
But instead of building a carbon skeleton from scratch to make new compounds, UChicago scientists have developed a new method where they can insert atoms within an already existing carbon framework.
The innovation comes from a paper recently published in Science, by Rui Zhang, a fifth-year graduate student with the Guangbin Dong Lab. Zhang, with assistance from undergraduate Tingting Yu, developed a new “hook and slide” strategy that promises to optimize medicinal chemistry.
“It could lead to fast access to different drug candidates and therefore save a lot of time in the drug discovery process,” said Zhang.
Back in May of 2021, Zhang began work on a problem having to do with how scientists create new molecules.
By tweaking the structure of molecules in a systematic way, scientists can explore how these changes affect the properties of the substances they are working with, providing a useful tool for tailoring molecules to specific needs in various applications. This is especially relevant in fields like drug development, where new lead-identification can potentially save lives.
“I think the first challenge I had was how to activate the amide, and then how to make the process efficient and controllable.”
—Chemist Rui Zhang
Hook and slide
With what Dong describes as a “hook and slide strategy,” they found the key to not only activate the bond, but to make the homologation process tunable.
Once Zhang nailed down the method for activation, he spent another two years honing the project, screening through different conditions, and finding more efficient ways to activate and create bonds.
With the publication in Science, he now feels that his work has finally paid off.
“We gained new knowledge about how to break this very inert carbon-carbon bond and we hope this can inspire the field to investigate more of this inert chemical bond activation,” Zhang said. “We hope this tells the community that if you design the strategy well and it has a great catalyst, even an inert bond can be manipulated.”
Reference: Zhang R, Yu T, Dong G. Rhodium catalyzed tunable amide homologation through a hook-and-slide strategy. Science. 2023;382(6673):951-957. doi: 10.1126/science.adk1001
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