Biomimetic Total Synthesis of Sarglamides A, B, C, Unnatural–Natural Sarglamide G, and Their Enantiomers

Herein, we report the first biomimetic asymmetric total synthesis of sarglamides A, B, and C, recently isolated from a shrub of the genus <i>Sarcandra</i>. Our synthesis features an efficient one-step intermolecular [4 + 2] Diels-Alder cycloaddition between (<i>S</i>)-α-phellandrene and both enantiomers of toussaintine C, which proceeds with <i>endo</i>-selectivity to give these 6/6/6/5 tetracyclic structures comprising seven stereogenic centers. By this approach, we also elaborated a sarglamide that had not been isolated, which we named sarglamide G. It resulted from the Diels-Alder reaction of (<i>S</i>)-α-phellandrene with (<i>R</i>,<i>R</i>)-toussaintine C via an <i>endo</i>-<i>ortho</i> transition state. Importantly, our study provides the shortest route to this family of unique indolidinoid-monoterpenoid hybrids as well as strong evidence to support their putative biosynthesis.