Diversified Synthesis of N -Benzoyl Piperidine Tetraoxane Analogues Using Molybdenum Trioxide as a Newer Catalyst and Its Antiplasmodial Activity.

Molybdenum trioxide has been proven to be an efficient catalyst in synthesizing mixed N -benzoyl piperidine dispiro-1,2,4,5-tetraoxane analogues using a one-pot reaction. This catalyst facilitated the synthesis of 21 tetraoxanes using cyclic, acyclic, and aromatic ketones. The structure and methodology of this reaction have been validated by single-crystal X-ray analysis of compound ″3g″. The nature of dispiro-1,2,4,5-tetraoxane being synthesized has an impact on the overall yield of tetraoxanes such as symmetric dispiro-1,2,4,5-tetraoxanes ranging from 53 to 82%, while yields of N -benzoyl piperidine dispiro-1,2,4,5-tetraoxanes ranged from 26 to 51%. Additionally, the in vitro antiplasmodial activity of the newly developed tetraoxanes against Plasmodium falciparum was assessed, which exhibited significantly higher activity in the nanomolar range, with values ranging from 6.35 to 44.65 nM. Molecular docking studies revealed that newer tetraoxane derivatives bind to the active site of the falcipain-2 enzyme through H-bonding and hydrophobic contacts, which are the primary indicators of the effectiveness of the synthesized compounds. Findings suggest that these peculiar compounds may act as antiplasmodial agents, which spur further study and advancement in the battle against malaria.