Pd-Catalysed [3+2]-cycloaddition towards the generation of bioactive bis-heterocycles/identification of COX-2 inhibitors via in silico analysis

In the current research, we envisaged the synthesis of bis-heterocycles containing the dihydroisoxazole ring by [3 + 2] cycloaddition of VECs (vinyl ethylene carbonates) and nitrile oxides, assisted by a Pd catalyst. Herein we explored hydroximoyl chlorides as versatile precursors for the in situ generation of nitrile oxides that were exploited to achieve the cycloaddition reaction on a vinyl group of VECs to generate bis-heterocycles. In silico-based studies of bis-heterocycles on the cyclooxygenase (COX) enzyme displayed selective COX-2 inhibition.

Automated summary

In this study, bis-heterocycles containing the dihydroisoxazole ring were synthesized through [3 + 2] cycloaddition reaction of VECs and nitrile oxides assisted by a Pd catalyst. Hydroximoyl chlorides were utilized as versatile precursors for the in situ generation of nitrile oxides, which underwent cycloaddition reaction on a vinyl group of VECs to form bis-heterocycles. Computational studies showed selective COX-2 inhibition of the synthesized bis-heterocycles.