Regioselective Pd-catalyzed decarboxylative C-6 acylation of 7-O-carbamate coumarins and their anti-inflammatory evaluation

O-Carbamate assisted Palladium (II) catalyzed regioselective C-H acylation of coumarins at C-6 position with arylglyoxylic acids has been achieved. The decarboxylative acylation of diverse 7-O-carbamate coumarins with wide range of arylglyoxylic acids produced solely the C-6 acylated coumarins. The synthesized molecules have been evaluated for their anti-inflammatory activity against RAW 264.7 macrophage cell line. Compounds 3aa, 3ab, and 3ia showed anti-inflammatory activity. Moreover, compound 3ia was found to be the most active with IC50 value of 5.471 mM in IL-1b expression. Further studies revealed that carbamate-based C-6 acylated coumarin derivatives 3aa, 3ab, and 3ia inhibits the nuclear translocation of p65 which mitigates the activation of inflammatory cascade by decreasing the expression of NF-kB. Compound 3ia was found to be the most active compound in inhibiting the NF-kB expression. (c) 2023 Elsevier Ltd. All rights reserved.

Automated summary

O-Carbamate assisted Palladium (II) catalyzed regioselective C-H acylation of coumarins at C-6 position with arylglyoxylic acids was achieved. The synthesized molecules showed anti-inflammatory activity, with compound 3ia being the most active in inhibiting NF-kB expression. Further studies demonstrated that carbamate-based C-6 acylated coumarin derivatives inhibited the nuclear translocation of p65, mitigating the activation of the inflammatory cascade.