Synthetic studies towards pentacyclic quassinoids: Total synthesis of unnatural (-)-14-epi-samaderine e and natural (-)-samaderine y from (S)-(+)-carvone

First total syntheses of unnatural (-)-14-epi-samaderine E (5) and natural (-)-samaderine Y (2) were accomplished from (5)-(+)-carvone (6) in 18 and 21 steps, respectively. The syntheses are short, efficient (with an average yield of 80% plus for each transformation), enantiospecific, and produce nine new chiral centers. The crucial points of the syntheses included a regioselective allylic oxidation on ring C, regio- and stereoselective reduction of ketone, a stereocontrolled epoxidation, an epoxymethano-bridge formation, a chemoselective Grignard reaction, an intramolecular Diels-Alder reaction, an intramolecular aldol addition, and a newly developed manganese(III)-catalyzed allylic oxidation on ring A.