A Practical Synthetic Route to Artepillin C and Drupanin

Synthesis of Artepillin C, a natural product with diverse biological activities, as well as Drupanin were accomplished. A two‐step continuous CuCN‐meditated prenylation of protected 3,5‐dibromo‐4‐hydroxybenzaldehyde, followed by HWE reaction efficiently provided desired diprenylated p‐cinnamic acid backbone structure. An efficient and practical route relying on a CuCN‐meditated prenylation reaction of o,o‐dihalophenol derivatives toward Artepillin C was proposed. The biprenyl side chain was efficiently introduced to the phenyl ring by two step continuous CuCN‐meditated prenylation. The second prenyl attachment was facilitated by organometallic stabilizer HMPA. HWE reaction was found effective for the extension of conjugated side chain. The 41% overall yield of the desired product was found to be the highest so far. In the meantime, the monoprenylated intermediate led us to another natural product Drupanin in satisfactory yield.