Total Synthesis of Morusalisin A

Morusalisin A is a nonclassical mulberry Diels-Alder-type adduct (MDAA) with a unique tricyclic skeleton. Herein, we report the first total synthesis of morusalisin A, accomplished in nine steps with an overall yield of 7.3% from commercially available 2,4,6-trihydroxybenzaldehyde. A key feature of the synthesis is a stereoselective intramolecular Diels-Alder (IMDA) reaction of the benzo-tethered butadienyl cinnamate, which efficiently constructs the tricyclic tetrahydro-6H-benzo[c]chromen-6-one core bearing three contiguous stereogenic centers. The pivotal point of the transformation was the strategic placement of a protecting group ortho on the diene moiety, which not only accommodated the IMDA but also controlled the stereochemical outcome. This study is expected to pave the way for broader application of the IMDA strategies in the synthesis of MDAAs, which have predominantly been accessed through intermolecular DA reactions.