Concise asymmetric syntheses of streptazone A and abikoviromycin

Streptazone A and abikoviromycin are related alkaloids that both feature an unusual arrangement of reactive functionalities within an underlying compact tricyclic ring system. Here, we report a highly concise asymmetric synthesis of both natural products. The developed route first constructs another member of the streptazones, streptazone B1, using a rhodium-catalyzed distal selective allene-ynamide Pauson-Khand reaction as the key transformation. A regio- and enantioselective epoxidation under chiral phase-transfer catalytic conditions was then achieved to directly make streptazone A in 8 steps overall. A chemoselective, iridium-catalyzed reduction of the enaminone-system was employed to make abikoviromycin in one additional step. Studies of the intrinsic reactivity of streptazone A towards the cysteine mimic, N-acetylcysteamine, revealed unanticipated transformations, resulting in thiol conjugation to both the hindered tertiary carbon of the double allylic epoxide and in 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.