Design and synthesis of a vialinin A analog with a potent inhibitory activity of TNF-α production and its transformation into a couple of bioprobes.

Abstract Vialinin A ( 1 ) is an extremely potent inhibitor against tumor necrosis factor (TNF)-α production in rat basophilic leukemia (RBL-2H3) cells. This Letter describes the design and synthesis of its advanced analog, 5′,6′-dimethyl-1,1′:4′1″-terphenyl-2′,3′,4,4″-tetraol ( 2 ) with a comparable inhibitory activity (IC 50  = 0.02 nM) to that of 1 . The synthesis involved double Suzuki–Miyaura coupling as a key step, and required only five steps from commercially available 3,4-dimethylphenol. For identification of the target molecule, fluorescent and biotinylated derivatives of 2 were prepared through a ‘click’ coupling process.