Research Projects

Small organic compounds with a heteroatom in their core constitute the main class of pharmacologically active agents and drug molecules, are the basis of life and their synthesis has always been full of excitement and challenges. Prof. Njardarson from the University of Arizona, USA recently summarized ten-year updates (2013-2023) on FDA-approved new small drug molecules (J. Med. Chem. 2024, 67, 11622−11655). i. 321 unique new small-molecule drugs approved from January 2013 to December 2023. ii. Incredible increase in drugs containing at least one nitrogen heterocycle-82%, compared to 59% from preceding decades. iii. Drugs containing two (33%), three (23%), or four (8%) nitrogen heterocycles and with two approved structures containing six nitrogen heterocycles. The above data indicate the importance of the nitrogen-containing small organic molecules and the efforts of chemists in this direction. In the past ten years, we have explored o-alkynyl aldehydes as a versatile synthon for constructing a wide range of small organic heterocyclic frameworks. 1,n-Enynes are versatile and valuable building blocks in organic synthesis and pharmaceutical industries because of their unique structural and reactivity properties. The annulation reaction of 1,n enynes has emerged as one of the most powerful and straightforward tools to build a carbo or heterocyclic framework of the desired nature in simple atom-economical steps. The combination of alkene and alkyne facilitates it to react with different substituents whether it is a radical cascade reaction, transition metal-catalyzed, or ionic reaction, they are suitable for the conversion making it a versatile reactant of interest for the scientific community. The geometry of the alkyne and alkene part favors it to react with numerous reactants, the linear geometry of the alkyne contrasts with the planar trigonal type geometry of alkene which leads to the generation of numerous stereochemical products. The possibility of having a terminal alkene or alkyne allows it to further functionalize. The application of enyne not only limits the synthesis of novel organic compounds used in natural products, pharmaceuticals, and agrochemical industries.5 It is used in polymer and material chemistry to create conjugated polymers which find applications in optoelectronics, sensors, and light-emitting diode (LED). Enynes also finds its application in drug discovery and catalysis research. Using the potential of enyne chemistry and our experience using such type of chemistry; in this project, we have proposed the construction of a wide range of small organic molecules of pharmaceutical interest. Proof of Concept: For the submitted project; we have established the proof of concept by developing a straightforward transition-metal-free sustainable methodology for oxidative cyclopropanation of aza-1,6-enynes, via four bond formation in a single step under mild conditions (Chem. Commun., 2024, 60, 9230-9233).