Chemists at the Okinawa Institute of Science and Technology Graduate University (OIST) have developed an organic catalyst capable of triggering reactions using pyruvate – a key biomolecule in many metabolic pathways – that are difficult and complicated to carried out using conventional industrial techniques.
The research, recently published in organic lettersis an important step towards simplifying the production process and increasing the range of molecules that can be built from pyruvate, such as amino acids or glycolic acids, which are used in drug discovery and research efforts. medications.
“Catalysts, substances that control and speed up chemical reactions without being included in the end products, are crucial tools for chemists,” said Santanu Mondal, a doctoral student in chemistry and chemical bioengineering at OIST and first author of the paper. ‘study. “And organic catalysts, in particular, are poised to revolutionize industry and make chemistry more sustainable.”
Currently, metal catalysts are used in industry, which are often expensive to obtain and produce hazardous waste. Metal catalysts also react easily with air and water, making them difficult to store and handle. But organic catalysts are formed from common elements, like carbon, hydrogen, oxygen and nitrogen, so they are much cheaper, safer and more environmentally friendly.
“In addition to these advantages, our newly developed organic catalyst system also promotes reactions using pyruvate that are not easily achievable with metal catalysts,” Santanu added.
In all chemical reactions, he explained, molecules can react either by giving up electrons or by receiving them. Pyruvate is much more apt to receive electrons when it reacts and is generally used in this way in industry, to produce alcohols and organic solvents. But in our bodies, protein catalysts called enzymes can cause reactions in which pyruvate donates electrons to produce molecules like fatty acids and amino acids.
Inspired by these enzymes, the researchers designed a catalytic system composed of two small organic molecules, an acid and an amine, which forces pyruvate to act as an electron donor.
In the reaction, the amine binds to the pyruvate, forming an intermediate molecule. The acid then covers part of the intermediate molecule, while leaving another part, which can donate electrons, free to react and form a new product.
It is important to note that the catalyst system is highly selective as to the form of product it will make. Like our hands, many biomolecules are asymmetrical and can exist in two forms that are mirror images of each other. These molecules look alike, but often have different properties.
“Organic catalysts can be designed so that at the end of the reaction, only one of these mirror-image forms is created,” Santanu said. “This is particularly beneficial in the pharmaceutical industry, where one form may be an effective treatment, but the other form may be toxic.”
For the pyruvate reactions, the researchers were able to selectively choose which of the two mirror image forms of the final product to make, by changing the mirror image form of the amine used to catalyze the reaction.
Currently, the organic catalyst system only works when reacting pyruvate with a specific class of organic molecules, called cyclic imines. But ultimately, the research team dreams of creating a next-generation catalyst for pyruvate that is universal, meaning it can speed up reactions between pyruvate and a wide range of organic molecules.
“With a universal catalyst, chemists could easily make a range of diverse products from pyruvate, in both mirror-image forms,” Santanu said. “It would have many significant impacts on society, such as accelerating the development of new drugs.”
Reference: Mondal S, Aher RD, Bethi V, et al. Control of pyruvate reactions by catalysts: Direct enantioselective Mannich reactions of pyruvates catalyzed by amine-based catalytic systems. Org Lett. 2022;24(9):1853-1858. doi: 10.1021/acs.orglett.2c00436
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