Total Synthesis of Ganoapplanin Enabled by a Radical Addition/Aldol Reaction Cascade
Nicolas Müller, Ondřej Kováč, Alexander Rode, Daniel Atzl, Thomas Magauer
Abstract
High Resolution Image Download MS PowerPoint Slide The total synthesis of the Ganoderma meroterpenoid ganoapplanin, an inhibitor of T-type voltage-gated calcium channels, is reported. Our synthetic approach is based on the convergent coupling of a readily available aromatic polyketide scaffold with a bicyclic terpenoid fragment. The three contiguous stereocenters of the terpenoid fragment, two of which are quaternary, were constructed by a diastereoselective, titanium-mediated iodolactonization. For the fusion of the two fragments and to simultaneously install the crucial biaryl bond, we devised a highly effective two-component coupling strategy. This event involves an intramolecular 6- exo -trig radical addition of a quinone monoacetal followed by an intermolecular aldol reaction. A strategic late-stage oxidation sequence allowed the selective installation of the remaining oxygen functionalities and the introduction of the characteristic spiro bisacetal structure of ganoapplanin.