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 <i>trans</i>-fused-2,6-<i>cis</i>-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 (C_10b) as a <i>cis</i>-fused-2,6-<i>cis</i>-THP motif. Notably, palladium-catalyzed arylation of Achmatowicz rearrangement products with boronic acids enables access to both 2,6-<i>trans</i>- and 2,6-<i>cis</i>-dihydropyrans (DHPs), corresponding to musellarins A-C and musellarins D-E, respectively.