Benzenoid ring C-H olefination of Coumarins under Rh(III)-catalysis: Synthesis, anti-inflammatory evaluation and in...

The C-H functionalization of coumarin benzenoid ring has been underexplored. In this study, we have carried out the Rh(III)-catalyzed C-H olefination on the benzenoid ring of coumarin at C8 and C6 position using O-carbamate directing group. The method is successfully applied to diverse range of coumarins and acrylates. Further, we have evaluated the synthesized compounds for their anti-inflammatory activity against tumor necrosis factor-alpha production in LPS-stimulated RAW264.7 macrophage cell line. Among the synthesized olefinated coumarin compounds, 4ea and 3ag were able to exhibit potent TNF-α expression inhibition, with IC₅₀ values of 6.297 μM and 11.87 μM, respectively. Further, compound 4ea was also found to inhibit the NF-kB expression. In addition, the interaction of the most potent compound 4ea with TNF-α dimer (PDB ID: 2AZ5) was elucidated by molecular docking and molecular simulation studies.