Concise Three Step Synthesis of the Bioactive Alkaloid Huajiaosimuline via a Zn(OTf)2 -Promoted Meinwald Rearrangement

The synthesis of the biologically active alkaloid huajiaosimulne, isolated from the roots of Zanthoxylum simulans, is reported. The natural product was assembled from simple commercial reagents via initial domino Knoevenagel/oxa-6π-electrocyclization followed by epoxidation and an epoxide/ketone rearrangement promoted by Zn(OTf)2. In vitro cytotoxicity assays identified natural products huajiaosimuline and simulansine as moderate antiproliferative agents against murine colon cancer CT26 cells.