Although Biginelli reaction is known to generate dihydropyrimidinones having wide arrays of phramacological properties, herein we report an unprecedented skeletal rearrangement in Biginelli reaction to synthesize pharmacologically versatile imidazolidine-2,4-diones, popularly known as hydantoins. Here a mixture of isatin, 4-hydroxycoumarin and 1,3-dimethylurea reacts in the presence of a catalytic amount of p-TsOH to generate spirohydantoins fused with chromenoquinoline moiety. Skeletal rearrangement of the 5-membered keto-lactam ring of isatin to a structurally constrained 5-membered ring in the form of spirohydantoins is the most interesting feature of this protocol. Nonetheless, the reaction introduces a novel molecular architecture bearing medicinally important spirohydantoin and chromenoquinoline scaffolds. In-silico molecular docking simulation of the synthesized compounds against human kinesin Eg5 (PDB ID: 2IEH) along with 17 other tumor-associated targets demonstrated strong binding efficiency, indicating that these compounds merit further biological evaluation to validate their anticancer potential.
Mezhubeinuo et al. (Sun,) studied this question.