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 Sarcandra. Our synthesis features an efficient one-step intermolecular [4+2] Diels-Alder cycloaddition between (S)-⍺-phellandrene and both enantiomers of toussaintine C, which proceeds with an endo-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 (S)-⍺-phellandrene with (R,R)-toussaintine C via an endo ortho 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.