IIT Delhi Researchers Develop Catalytic Technology for Sustainable Production of Chiral Active Pharmaceutical Ingredients

New Delhi: India is heavily dependent on importing (~85%) Active Pharmaceutical Ingredients (APIs), and a significant proportion of those APIs are chiral molecules, which are essential building blocks to produce pharmaceuticals, agrochemicals and biologically active compounds.

An IIT Delhi research group led by Prof. Kuntal Manna from the Department of Chemistry and his PhD students –Neha Antil and Rajashree Newar– has developed a catalytic technology for the sustainable and economical synthesis of chiral molecules. The Science and Engineering Research Board (SERB), a statutory body of the Department of Science and Technology (DST), Government of India, has funded this research work.

“The developed catalytic technology may play a crucial role in decreasing the country’s dependence on the import of the Active Pharmaceutical Ingredients, which also means lowering of the input cost for the industry that would encourage it to pass on the benefit to the society,” said Prof. Kuntal Manna, Chemistry Dept., IIT Delhi.

Chiral molecules exist as paired stereoisomers, known as enantiomers, that form mirror images of each other. The classical synthesis of chiral small molecule APIs results in mixtures of paired enantiomers.

However, two enantiomeric forms of a chiral API exhibit different biological properties, efficacies, and toxicities. One enantiomeric form may be harmful, while the other form is the desired active ingredient for the drug. Therefore, it is imperative that the intended API should be present in enantiomerically pure form in the drug.
In the pharmaceutical industry, the single enantiomers of chiral APIs are produced by separating the enantiomeric mixture or directly converting the raw material to the desired enantiomer selectively using a catalyst. The industrially used catalysts for such enantioselective transformations are mostly homogeneous and composed of expensive chiral ligands and precious and toxic metals such as iridium, ruthenium, palladium, or rhodium.

Unfortunately, both the methodologies are costly and not eco-friendly. To tackle this problem, the research team developed a Metal-Organic Frameworks (MOFs) based catalytic technology using inexpensive natural feedstocks and abundant metals for the sustainable and economical synthesis of enantiomerically pure chiral molecules.

Prof. Manna believes that the development of MOF-based earth-abundant metal catalysts has the potential for cost-effective and environmentally benign domestic production of enantiopure chiral APIs.

The work was published in reputed journals such as Angewandte Chemie International Edition, 60, 10964–10970 (2021)- https://onlinelibrary.wiley.com/doi/10.1002/anie.202100643 and ACS Catalysis, 11, 10450–10459 (2021)-https://pubs.acs.org/doi/10.1021/acscatal.1c02529.

 

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