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Concise Asymmetric Syntheses of Streptazone A and Abikoviromycin **
Author(s) -
Wørmer Gustav J.,
Villadsen Nikolaj L.,
Nørby Peter,
Poulsen Thomas B.
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202101439
Subject(s) - allene , enantioselective synthesis , chemistry , rhodium , combinatorial chemistry , iridium , catalysis , reactivity (psychology) , ring (chemistry) , thiol , stereochemistry , transfer hydrogenation , organic chemistry , ruthenium , medicine , alternative medicine , pathology
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 B 1 , 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.