Dr Akkattu T Biju, associate professor of organic chemistry at IISc Bengaluru, is one of the two winners of the Shanti Swarup Bhatnagar Prize for Chemical Sciences for 2023. Like the other winner, Debabrata Maiti of IIT Bombay, Dr Biju too develops new strategies for pharmaceutically valuable molecules.
Dr Biju was awarded the prestigious prize for his work on transition-metal-free carbon-carbon and carbon-heteroatom bond formation reactions using aryne chemistry and carbene-based organocatalysis. His research group has used aryne chemistry to synthesise biologically important 1,2-disubstituted arenes, as well as nucleophilic heterocyclic carbene-based catalytic techniques to build various heterocyclic compounds as a single enantiomer.
Through the use of carbene catalysis in non-traditional carbon-carbon bond-forming reactions, new pathways for the synthesis of valuable heterocyclic compounds and drug-like molecules have been made possible.
In order to avoid using transition metals for catalysis, Dr Biju’s group uses novel organocatalysis and aryne chemistry. Organocatalysis is the use of small organic molecules as catalysts. This removes the possibility that pharmaceuticals may contain trace metals, which raises issues with product safety and adherence to regulatory requirements. Additionally, the mild operating conditions of organocatalysed reactions minimise energy consumption and environmental impact. Conversely, aryne chemistry describes the synthesis of highly functionalised benzene derivatives—compounds with significant medicinal implications—by means of a particular class of compounds.
To perform specific transformations, the group uses NHC (Nucleophilic Heterocyclic Carbene) as the organocatalyst. A molecule known as a carbene has a carbon atom with two available electrons for bonding. Their polarity—a term used to describe whether an atom in a reaction is positively or negatively charged—can be reversed through interactions with aldehydes.
Aldehydes usually contain a partially positive carbon atom and a partially negative oxygen atom. Nevertheless, carbenes have the ability to reverse this polarity when they react with aldehydes. This makes it possible for new kinds of reactions to happen that otherwise would not have been possible. Organocatalysis was recognised as a very important and useful technique in 2021, and two of its pioneers—Benjamin List and David MacMillan—were given the 2021 Nobel Prize for Chemistry for their revolutionary work in this field.
NHCs were previously only used to reverse the polarity of aldehydes. Dr Biju’s group was the first to employ NHCs in 2017 to reverse the polarity of imines, a different class of compounds. Unprotected indole derivatives are biologically important compounds that were synthesised using this innovative chemistry. Later, in order to produce chiral molecules, Dr Biju’s group extended the idea of polarity reversal in imines. Prominent organic chemists around the world adopted this idea of using NHC as an organocatalyst, which sparked the creation of a number of cutting-edge techniques for the synthesis of biologically important compounds.
Dr Biju’s group is developing transition-metal-free processes for a range of reactions that form bonds between carbon atoms and heteroatoms. These techniques are extremely relevant in the drug discovery process as well as the pharmaceutical and agrochemical industries because they are not only adaptable and efficient but also sustainable.
The agrochemical industry is interested in using one of his noteworthy contributions to aryne chemistry to synthesise different nitrogen heterocycles. Their desire to develop new pesticides has prompted them to make use of the bicyclic molecules that Dr Biju’s team has synthesised. Apart from its research endeavours, the team has written two books on aryne chemistry and NHC catalysis, with an aim to simplify these intricate subjects for a broader audience.
