Gustav J. Wørmer Dr. Nikolaj L. Villadsen Dr. Peter Nørby Prof. Dr. Thomas B. Poulsen
Angew. Chem. Int. Ed. 2021
https://doi.org/10.1002/anie.202101439
Streptazone A and abikoviromycin are alkaloids that both feature an unusual arrangement of reactive functionalities within a compact tricyclic ring system. Here, we report a highly concise asymmetric synthesis of both natural products. The route first constructs another family member, streptazone B1, using a rhodium‐catalyzed distal selective allene‐ynamide Pauson–Khand reaction. A regio‐ and enantioselective epoxidation under chiral phase‐transfer catalytic conditions directly afforded streptazone A in 8 steps overall. In one additional step, a chemoselective, iridium‐catalyzed reduction of the enaminone system then gave abikoviromycin. The reactivity of streptazone A towards a cysteine mimic, N‐acetylcysteamine, was studied and revealed unanticipated transformations, including bis‐thiol conjugation which may proceed via formation of a cyclopentadienone intermediate. With flexible access to these compounds, studies aimed to identify their direct biological targets are now possible.
