Department of Chemistry
Gold-catalyzed cycloisomerization and diels–alder reaction of 1,4,9-dienyne esters to 3 a,6-methanoisoindole esters with pro-inflammatory cytokine antagonist activity
A synthetic method to prepare 3a,6-methanoisoindole esters efficiently by gold(I)-catalyzed tandem 1,2-acyloxy migration/Nazarov cyclization followed by Diels–Alder reaction of 1,4,9-dienyne esters is described. We also report the ability of one example to inhibit binding of tumor necrosis factor-α (TNF-α) to the tumor necrosis factor receptor 1 (TNFR1) site and TNF-α-induced nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) activation in cell at a half-maximal inhibitory concentration (IC50) value of 6.6 μM. Along with this is a study showing the isoindolyl derivative to exhibit low toxicity toward human hepatocellular liver carcinoma (HepG2) cells and its possible mode of activity based on molecular modeling analysis.
alkynes, cycloisomerization, cytokine antagonists, gold, homogeneous catalysis
Source Publication Title
Chemistry - A European Journal
Link to Publisher's Edition
Susanti, D., Liu, L., Rao, W., Lin, S., Ma, D., Leung, C., & Chan, P. (2015). Gold-catalyzed cycloisomerization and diels–alder reaction of 1,4,9-dienyne esters to 3 a,6-methanoisoindole esters with pro-inflammatory cytokine antagonist activity. Chemistry - A European Journal, 21 (25), 9111-9118. https://doi.org/10.1002/chem.201500795