Development of a Triethylborane-Mediated Giese Cyclization/Aldol Reaction Cascade for the Total Synthesis of Ganoapplanin

We present our synthetic endeavors towards the <i>Ganoderma</i> meroterpenoid ganoapplanin. This natural product was isolated from a <i>Ganoderma</i> fungus in 2016 and was found to be an inhibitor for T-type voltage-gated calcium channels. Our synthetic approach is based on a powerful intramolecular Giese cyclization/intermolecular aldol cascade to link the northern aromatic to the southern terpenoid fragment. This article highlights the synthetic studies that ultimately led to the successful development of the key cascade reaction, culminating in the first total synthesis of ganoapplanin. 1Introduction2Synthesis of the Southern Terpenoid Fragment3Synthesis of the Northern Terpenoid Fragment4Triethylborane Mediated Giese Cyclization/Aldol Reaction Cascades5Completion of the Total Synthesis of Ganoapplanin6Conclusion.