Collective Asymmetric Total Syntheses of Musellarins A–E

Musellarins represent a rare class of diarylheptanoid natural products with cytotoxic activity. While total synthesis of musellarins A-C has been reported, musellarins D and E with trans-fused-2,6-cis-dihydropyran (DHP) remain synthetically unexplored. An Achmatowicz rearrangement-based synthetic strategy is developed for the collective total synthesis of musellarins A-E, where synthetic musellarins D and E are achieved for the first time and allow us to correct the misassigned configuration of carbon-10b (C10b) as a cis-fused-2,6-cis-THP motif. Notably, palladium-catalyzed arylation of Achmatowicz rearrangement products with boronic acids enables access to both 2,6-trans- and 2,6-cis-dihydropyrans (DHPs), corresponding to musellarins A-C and musellarins D-E, respectively.