The tetracyclic meroterpenoid natural product (＋)-liphagal is one of a number of natural inhibitors of phosphatidylinositol 3-kinase (PI3K), which plays a central role in regulation of cell proliferation, cell survival, adhesion, membrane trafficking, glucose transport and neurite growth. Liphagal also shows inhibitory activity against PI3Kα with an IC₅₀ of 100 nmol·L^-1 making it as an agent for the treatment of inflammatory and autoimmune disorders as well as cancer and cardiovascular diseases. From a structural point of view, liphagal has an unprecedented [6-7-5-6] tetracyclic skeleton, and has attracted significant attention from the synthetic chemists. Starting from cheap and commercially available 2,4,5-trimethoxylbenzaldehyde and α-ionone, an advanced intermediate 10 for the synthesis of 8-epi-liphagal was achieved in the longest linear 7 steps and 8.72% yield. The key reactions include: Wittig reaction, Cu-catalyzed cyclization, chemoselective hydrogenation and Friedel-Crafts reaction.

Key words: liphagal, natural product, synthesis, Friedel-Crafts reaction, advanced intermediates