2-Aminooxazoles and 2-aminothiazoles: green regioselective synthesis and bioactivity

2-Aminooxazole and 2-aminothiazole are heterocyclic compounds that can be developed to be therapeutically significant in medicinal chemistry as they are associated with a myriad of biologically important multicentric activities such as anticancer, anti-viral, anti-bacterial, anti-fungal, and enzyme inhibition. Chemically, they have been reported to target critical enzymes such as CDKs, aurora kinases, DHPS, and proteases. However, traditional routes to construct heterocyclic compounds are fraught with difficulties, such as poor regioselective control, producing C-4/C-5 regioisomeric mixtures, poor atom economy, laborious purifications, and a substantial waste of solvents. Recently developed green synthetic approaches, such as microwave-assisted synthesis, ultrasound activation, multicomponent reactions, nanocatalysis, and newer techniques that employ syntheses in aqueous media and in a solvent-free manner, have attempted to address these issues. These methods provide better regioselectivity, better reaction efficiencies, and better yields. In the context of synthetic medicinal chemistry, the green approaches enhance the safety and convenience of laboratory operations by decreasing the need for hazardous solvents. However, the absence of the E-factor, PMI, and atom economy, as well as the substrate-dependent regioselective variability in these methodologies, has restricted the comparison of these methodologies as a whole, and their application in the pharmaceutical industry on a large scale.