Sustainable Synthesis of Quinolones and the Main Based-Drug Ivacaftor by Aquoline

The classic drug synthesis methods applied by the pharmaceutical industry are a major source of toxic and environmentally harmful waste. Although the continuous search for increasingly effective drugs is essential, chemists and chemical engineers involved in production processes have a responsibility to adopt practices aligned with the principles of green chemistry. In this context, aquiline, a combination of choline chloride (ChCl) and water in a 1:3.33 molar ratio, representing one of the earliest examples of natural deep eutectic solvents (NADES) and water-in-salt (WiS) systems, is explored under different conditions as an environmental reaction medium for the synthesis of several 4-quinolone derivatives. These compounds represent key pharmacophores and essential intermediates in the development of various drugs. Notably, the same reaction system is crucial to obtain Ivacaftor, a commercially available drug for managing cystic fibrosis (CF).