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 (IC50=0.02nM) 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.