Many active ingredients in medications, known as small molecules, primarily composed of carbon, are larger than water but much smaller than antibodies. However, manufacturing these molecules becomes challenging when they require quaternary carbons (carbon atoms directly connected to four other carbon atoms). Now, scientists at the Scripps Research Institute in the United States have uncovered a potential low-cost method for creating these complex structures.
On April 5th, the journal Science published the research findings, demonstrating that it is possible to convert raw chemicals into quaternary carbons using an inexpensive iron catalyst. This approach could facilitate easier production of molecules at both small and large scales, benefiting drug developers.
Image Source: Scripps Research
"From drug discovery to materials science, quaternary carbons are ubiquitous across various research fields," said Nathan Dao, co-first author of the paper and doctoral student at Scripps Research. "However, the synthesis of quaternary carbons has been a longstanding challenge in organic chemistry, often requiring numerous steps and relying on harsh conditions or hard-to-obtain starting materials."
Catalysts are substances used to accelerate the rate of chemical reactions. Sometimes, several different catalysts are needed to promote a specific reaction and achieve the desired outcome. However, catalysts can be prohibitively expensive, and they don't always perform as expected. The more catalysts used, the more waste is generated. But scientists at Scripps Research believe that one catalyst can serve multiple crucial roles.
"A challenging chemical reaction typically requires many interacting components. One advantage of our work is its simplicity," said Ryan Shenvi, corresponding author of the paper and professor in the Department of Chemistry at Scripps Research.
The team identified a straightforward pathway to convert carboxylic acids and olefins, two major chemical feedstocks, into quaternary carbons using inexpensive iron-based catalysts. Moreover, these chemical feedstocks are not only abundant but also cost-effective.
"Similar reactions have been gaining popularity lately, so this discovery was inevitable. These fragments have appeared in some literature, but no one has previously combined them," explained Shenvi.
Baran, professor in the Department of Chemistry at Scripps Research, added, "This work reveals new transformations that could have a significant impact on simplifying organic synthesis practices."
Related paper information: https://doi.org/10.1126/science.adn5619
