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

• Main Authors: Susanti, Dewi, Liu, Li-Juan, Rao, Weidong, Lin, Sheng, Ma, Dik-Lung, Leung, Chung-Hang, Chan, Philip Wai Hong
• Other Authors: School of Physical and Mathematical Sciences
• Format: Article
• Language: English
• Published: 2015
• Subjects: DRNTU::Science::Chemistry::Physical chemistry::Catalysis
• Online Access: https://hdl.handle.net/10356/103024; http://hdl.handle.net/10220/25763
• Institution: Nanyang Technological University

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.