Asymmetric Total Synthesis of Toxicodenane A by Samarium-Iodide-Induced Barbier-Type Cyclization and Its Cell-Protective Effect against Lipotoxicity.

The asymmetric total synthesis of toxicodenane A, a sesquiterpenoid expected to be promising for diabetic nephropathy, was achieved. In the synthesis, a samarium iodide (SmI2)-induced Barbier-type cyclization and a regio- and stereoselective allylic oxidation followed by a dehydration cyclization were employed as key steps. Furthermore, the first asymmetric syntheses of both enantiomers were accomplished using the previously mentioned synthetic strategy. Finally, the synthetic compounds significantly inhibited lipotoxicity-mediated inflammatory and fibrotic responses in mouse renal proximal tubular cells.